Microfluidic chip
The microchannel chip design addresses adhesive leakage by welding a partition layer and upper lid without adhesives, ensuring reaction integrity and simplifying manufacturing.
Patent Information
- Application Number
- JP2021122578
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2021-07-27
- Publication Date
- 2025-08-13
- Estimated Expiration
- 2041-07-27
AI Technical Summary
Existing microchannel chips bonded via adhesives face issues with adhesive components leaching into the solution, inhibiting reactions within the channel.
A microchannel chip design that welds a partition layer and an upper lid without an adhesive, using a resin with thermal fluidity to form the lid, and incorporates rounded channel corners to prevent adhesive leakage.
Prevents adhesive components from eluting into the channel, thereby suppressing reaction inhibition and simplifying the manufacturing process.
Smart Images

Figure 0007722011000001 
Figure 0007722011000002 
Figure 0007722011000003
Abstract
Description
[Technical Field]
[0001] The present disclosure relates to a microchannel chip and a method for manufacturing the same. [Background technology]
[0002] In recent years, a new technology has been proposed that uses lithography and thick film processing techniques to form minute reaction fields, enabling testing in the order of a few μL to a few nL. This technology, which utilizes such minute reaction fields, is called μ-TAS (Micro Total Analysis System).
[0003] μ-TAS is applied in areas such as genetic testing, chromosome testing, cell testing, pharmaceutical development, biotechnology, testing for trace substances in the environment, investigation of the rearing environment of agricultural crops, genetic testing of agricultural crops, etc. The introduction of μ-TAS technology will bring about significant benefits such as automation, high speed, high precision, low cost, rapidity, and reduced environmental impact.
[0004] μ-TAS often uses micrometer-sized flow paths (microflow paths, microchannels) formed on a substrate, and such substrates are called chips, microchips, microflow path chips, etc.
[0005] Conventionally, such microchannel chips are fabricated by bonding together multiple components, such as glass, plastic, resin, and metal. A common bonding method involves bonding these components together using an intermediate material other than these components. Here, a so-called adhesive is used as the intermediate material. In this case, after forming a channel on the surface of one component (e.g., the surface of a substrate), an adhesive is applied to the surface of the wall that forms the channel, and the other component, which serves as a channel lid, is attached to bond the components together to fabricate a microchannel chip.
[0006] For example, Patent Document 1 discloses a microchannel chip that is bonded via an adhesive. [Prior art documents] [Patent documents]
[0007] [Patent Document 1] Japanese Patent Application Laid-Open No. 2007-240461 Summary of the Invention [Problem to be solved by the invention]
[0008] In a microchannel chip formed by a method of joining components together via an adhesive as disclosed in Patent Document 1, there is a problem in that components of the adhesive may leach into the solution flowing through the microchannel, which may inhibit the reaction of the solution. For this reason, in recent years, there has been a demand for forming a lid for a microchannel chip without using an adhesive, that is, for preventing the adhesive component from eluting into the channel.
[0009] Therefore, in view of the above problems, the present disclosure aims to provide a microchannel chip that can prevent adhesive components from leaching into the channel and suppress reaction inhibition of the solution in the channel, and a method for manufacturing the same. [Means for solving the problem]
[0010] In order to solve the above problems, a micro-channel chip according to one aspect of the present disclosure includes a base portion and The device is characterized in that it comprises a partition layer that forms a flow path on the base, and an upper lid that is formed on the surface of the partition opposite the base and serves as a lid for the flow path, and no adhesive layer is provided between the partition and the upper lid. In order to solve the above-mentioned problems, a microchannel chip according to another aspect of the present disclosure includes a base, a partition wall portion that forms a channel on the base, and a top cover portion that is formed on the surface of the partition wall layer opposite the substrate and serves as a lid for the channel, and is characterized in that the top cover portion and the partition wall portion are welded to each other. In addition, in order to solve the above-mentioned problems, a microchannel chip according to yet another aspect of the present disclosure is a microchannel chip comprising a channel and a top cover portion that serves as a lid for the channel, wherein the material of the top cover portion is a resin having thermal fluidity, and the cross-sectional shape of the channel has rounded corners.
[0011] Furthermore, a method for manufacturing a microchannel chip according to one aspect of the present disclosure is characterized by including the steps of applying a photosensitive resin onto a base, exposing the applied photosensitive resin to light, developing and washing the exposed photosensitive resin to form a partition wall portion that defines a channel on the base, and heating the partition wall portion to cause the photosensitive resin to flow and form a top cover portion of the channel. Furthermore, a method for manufacturing a microchannel chip according to another aspect of the present disclosure is characterized by including the steps of: applying a first photosensitive resin onto a base; applying a second photosensitive resin onto the applied first photosensitive resin; exposing the first photosensitive resin and the second photosensitive resin to light; developing and washing the exposed first photosensitive resin and the second photosensitive resin to form a partition wall portion that defines a channel on the base; and heat-treating the second photosensitive resin on the partition wall to cause the second photosensitive resin to flow, thereby forming a top cover portion of the channel. [Effects of the Invention]
[0012] According to an aspect of the present disclosure, it is possible to provide a microchannel chip that can prevent adhesive components from eluting into the channel and suppress reaction inhibition of the solution in the channel. [Brief explanation of the drawings]
[0013] [Figure 1] 1A and 1B are schematic diagrams showing an example of the configuration of a micro-channel chip according to a first embodiment of the present disclosure, in which FIG. 1A is a schematic plan view showing the example of the configuration of a micro-channel chip according to a first embodiment of the present disclosure, and FIG. 1B is a schematic cross-sectional view showing the example of the configuration of a micro-channel chip according to a first embodiment of the present disclosure. [Figure 2]FIG. 2 is a cross-sectional schematic view showing an example of the cross-sectional shape of a channel of the micro-channel chip according to the first embodiment of the present disclosure. [Figure 3] FIG. 1 is an enlarged schematic cross-sectional view showing a cross section of a micro-channel chip according to a first embodiment of the present disclosure. [Figure 4] 1 is a flowchart showing an example of a method for manufacturing a micro-channel chip according to a first embodiment of the present disclosure. [Figure 5] 1A and 1B are diagrams illustrating a part of a manufacturing process of a microchannel chip by a manufacturing method according to a first embodiment of the present disclosure, in which (a) is a schematic cross-sectional view showing a resin material applied onto a substrate, (b) is a schematic cross-sectional view showing a groove portion formed between partition layers, and (c) is a schematic cross-sectional view showing an example of a microchannel chip produced by the manufacturing method. [Figure 6] 1A and 1B are diagrams illustrating a manufacturing process of a micro-channel chip by another manufacturing method according to a first embodiment of the present disclosure, in which (a) is a schematic cross-sectional view showing a resin material applied to a substrate, (b) is a schematic cross-sectional view showing a groove portion formed between partition portions, and (c) is a schematic cross-sectional view showing an example of a micro-channel chip produced by one manufacturing method. [Figure 7] 1A and 1B are diagrams illustrating a manufacturing process of a micro-channel chip by yet another manufacturing method according to the first embodiment of the present disclosure, in which (a) is a schematic cross-sectional view showing a resin material applied to a substrate, (b) is a schematic cross-sectional view showing a groove portion formed between partition portions, and (c) is a schematic cross-sectional view showing an example of a micro-channel chip produced by one manufacturing method. [Figure 8] FIG. 10 is a cross-sectional schematic view showing an example of the cross-sectional shape of a channel of a micro-channel chip according to a second embodiment of the present disclosure. [Figure 9]10A and 10B are diagrams illustrating a manufacturing process of a micro-channel chip by one manufacturing method of a micro-channel chip according to a second embodiment of the present disclosure, in which (a) is a schematic plan view showing an example of a channel pattern, (b) is a schematic cross-sectional view of an input region of the channel pattern, (c) is a schematic cross-sectional view of a channel region of the channel pattern, (d) is a schematic plan view of a micro-channel chip manufactured by one manufacturing method, (e) is a schematic cross-sectional view of an input part of the micro-channel chip manufactured by one manufacturing method, and (f) is a schematic cross-sectional view of a channel part of the micro-channel chip manufactured by one manufacturing method. [Figure 10] FIG. 1(a) is a cross-sectional SEM image of a micro-channel chip according to an example before post-baking, and FIG. 1(b) is a cross-sectional SEM image of a micro-channel chip according to an example after post-baking. DETAILED DESCRIPTION OF THE INVENTION
[0014] The present disclosure will be described below through embodiments, but the following embodiments do not limit the invention according to the claims. Furthermore, not all of the combinations of features described in the embodiments are necessarily essential to the solution of the invention. Furthermore, the drawings are merely schematic illustrations of the invention according to the claims, and the dimensions of the width, thickness, etc. of each part may differ from the actual dimensions, and the ratios between these dimensions may also differ from the actual dimensions.
[0015] A micro-channel chip according to a first embodiment of the present disclosure will be described. In the following description, the substrate side of the micro-channel chip may be referred to as "bottom" and the side opposite the substrate side (lid side) of the micro-channel chip may be referred to as "top."
[0016] As a result of extensive research, the present inventors have found that by forming a top cover portion that serves as a lid for a channel portion in a microchannel chip by heating and flowing a resin material, it is possible to provide the top cover on a partition portion without using an adhesive. As a result, the present inventors have invented a microchannel chip and a method for manufacturing the same that can prevent the adhesive component from eluting into the channel and suppress reaction inhibition of the solution in the channel. Hereinafter, each aspect of each embodiment of the present disclosure will be described with reference to the drawings.
[0017] 1. First embodiment (1.1) Basic structure of a microfluidic chip Fig. 1 is a schematic diagram illustrating one configuration example of a micro-channel chip 1 according to a first embodiment of the present disclosure (hereinafter referred to as "this embodiment"). Specifically, Fig. 1(a) is a schematic plan view of the micro-channel chip 1 of this embodiment. Fig. 1(b) is a schematic cross-sectional view showing a cross section of the micro-channel chip 1 taken along line AA shown in Fig. 1(a).
[0018] 1(a), micro-channel chip 1 includes an input section 2 for introducing a fluid (e.g., a liquid), a channel section 3 through which the fluid introduced from input section 2 flows, and an output section 4 for discharging the fluid from channel section 3. In micro-channel chip 1, the upper surface of channel section 3 is covered with an upper cover layer 12, and input section 2 and output section 4 are through-holes provided in upper cover layer 12. Details of upper cover layer 12 will be described later. FIG. 1(a) shows the flow path portion 3 visible through the transparent upper cover layer 12.
[0019] Micro-channel chip 1 may be provided with at least one input section 2 and one output section 4, and may be provided with a plurality of each. Micro-channel chip 1 may be provided with a plurality of channel sections 3, and may be designed to allow the joining and separation of fluids introduced from input section 2.
[0020] Here, details of the components that make up the channel section 3 in the micro-channel chip 1 will be described. As shown in Fig. 1(b), the micro-channel chip 1 includes a substrate (an example of a base section) 10, a partition layer (an example of a partition section) 11 that forms a channel on the substrate 10, and an upper cover layer (an example of an upper cover section) 12 that is formed on the surface of the partition layer 11 opposite to the substrate 10 and serves as a lid for the channel section 3. In the microchannel chip 1, the channel section 3, through which the fluid introduced from the input section 2 flows, is an area surrounded by the substrate 10, the partition layer 11, and the upper cover layer 12. The channel section 3 is defined by opposing partition layers 11 provided on the substrate 10, and is covered on the side opposite the substrate 10 by the upper cover layer 12, which serves as a lid material. In other words, the channel section 3 is a space formed by the substrate 10, the partition layer 11, and the upper cover layer 12. As described above, the fluid is introduced into the channel section 3 from the input section 2 (see FIG. 1(a)) provided on the upper cover layer 12, and the fluid that has flowed through the channel section 3 is discharged from the output section 4. As will be described in more detail below, in micro-channel chip 1 according to this embodiment, no adhesive layer is provided between partition layer 11 and upper cover layer 12. In this embodiment, partition layer 11 and upper cover layer 12 are welded to each other. Here, the adhesive layer is a layer containing an adhesive, and is used to bond multiple components together. By welding (bonding) partition layer 11 and upper cover layer 12 without providing an adhesive layer between them, micro-channel chip 1 can prevent adhesive components from eluting into the channels and suppress reaction inhibition of the solution in the channels.
[0021] 1(b), partition wall layer 11 and top cover layer 12 are separate bodies. Here, "separate bodies" means, for example, that partition wall layer 11 and top cover layer 12 are formed from different resin materials. In this case, the resin material forming top cover layer 12 can be selected from a material that has properties suitable for an upper cover, such as a glass transition temperature or exposure sensitivity different from that of partition wall layer 11. The present disclosure is not limited to this, and partition wall layer 11 and top cover layer 12 may be separate bodies when they have a laminated structure and an interface is formed between them. In this case, partition wall layer 11 and top cover layer 12 may be formed from the same resin material.
[0022] (1.1.1) Substrate Substrate 10 is a base member of micro-channel chip 1, and channel section 3 is formed by partition layer 11 provided on substrate 10. In other words, substrate 10 and partition layer 11 can be said to be the main body of micro-channel chip 1. Substrate 10 can be made of either a light-transmitting material or a light-non-transmitting material. For example, when the state (fluid state) inside flow channel section 3 is detected or observed using light, a material that is highly transparent to the light can be used. Examples of light-transmitting materials that can be used include resin and glass. Resins used as the light-transmitting material for forming substrate 10 include acrylic resin, methacrylic resin, polypropylene, polycarbonate resin, cycloolefin resin, polystyrene resin, polyester resin, urethane resin, silicone resin, and fluorine-based resin, which are suitable for forming the main body section of micro-channel chip 1.
[0023] Furthermore, for example, if there is no need to detect or observe the state (fluid state) inside the flow path section 3 using light, a non-light-transmitting material may be used. Examples of non-light-transmitting materials include a silicon wafer and a copper plate. The thickness of the substrate 10 is not particularly limited, but since a certain degree of rigidity is required in the flow path formation process, it is preferably within the range of 10 μm (0.01 mm) to 10 mm.
[0024] (1.1.2) Partition layer The partition layer 11 is provided on the substrate and forms the flow path portion 3. The partition layer 11 can be made of a resin material. As the resin material for the partition layer 11, for example, a photosensitive resin can be used.
[0025] The photosensitive resin forming the partition layer 11 is preferably a photosensitive resin that is sensitive to light with a wavelength of 190 nm or more and 400 nm or less, which is the ultraviolet light region. Examples of such photosensitive resins include photoresists such as liquid resists and dry film resists. These photosensitive resins may be either positive-type, in which the photosensitive region dissolves, or negative-type, in which the photosensitive region is insolubilized. Examples of photosensitive resin compositions suitable for forming the partition layer 11 in the microchannel chip 1 include radical negative-type photosensitive resins containing an alkali-soluble polymer, an addition-polymerizable monomer, and a photopolymerization initiator. Examples of photosensitive resin materials include acrylic resins, epoxy resins, polyamide resins, polyimide resins, polyurethane resins, polyester resins, polyether resins, polyolefin resins, polycarbonate resins, polystyrene resins, norbornene resins, phenol novolac resins, and other photosensitive resins, which can be used alone or in combination or copolymerized. In this embodiment, the resin material of the partition layer 11 is not limited to photosensitive resin, and may be, for example, silicone rubber (PDMS: polydimethylsiloxane) or synthetic resin. Examples of synthetic resins that can be used include polymethylmethacrylate resin (PMMA), polycarbonate (PC), polystyrene resin (PS), polypropylene (PP), cycloolefin polymer (COP), and cycloolefin copolymer (COC). It is desirable to select the resin material of the partition layer 11 appropriately depending on the application. Furthermore, the thickness of the partition layer 11 on the substrate 10, i.e., the height of the flow path section 3, is not particularly limited, but the height of the flow path section 3 needs to be greater than the substance to be analyzed or inspected (e.g., drugs, bacteria, cells, red blood cells, white blood cells, etc.) contained in the fluid introduced into the flow path section 3. For this reason, the thickness of the partition layer 11, i.e., the height (depth) of the flow path section 3, is preferably in the range of 1 μm to 500 μm, more preferably in the range of 10 μm to 100 μm, and even more preferably in the range of 40 μm to 60 μm. Similarly, since the width of the flow path section 3 needs to be larger than the substance to be analyzed or inspected, the width of the flow path section 3 defined by the partition layer 11 is preferably in the range of 1 μm to 500 μm, more preferably in the range of 10 μm to 100 μm, and even more preferably in the range of 10 μm to 30 μm. Furthermore, the length of the flow path determined by the partition layer 11 is preferably within a range of 10 mm to 100 mm, more preferably within a range of 30 mm to 70 mm, and even more preferably within a range of 40 mm to 60 mm, in order to ensure a sufficient reaction time for the reaction solution.
[0026] (1.1.3) Upper lid layer In the micro-channel chip 1 according to this embodiment, the upper cover layer 12 is a cover material that covers the channel section 3, as shown in Figures 1(a) and 1(b). As described above, the upper cover layer 12 is provided on the surface of the partition layer 11 opposite the substrate 10, and faces the substrate 10 across the partition layer 11. More specifically, as shown in Figure 1(b), in a cross-sectional view, the side edges of the upper cover layer 12 are supported by the partition layer 11, and the central region faces the substrate 10, and this central region defines the upper part of the channel section 3.
[0027] The upper cover layer 12 can be formed from either a light-transmitting material or a light-non-transmitting material. For example, when the state inside the flow channel is detected or observed by light, a material that is highly transparent to the light can be used. The light-transmitting material can be a resin. The resin that forms the upper cover layer 12 can be a photosensitive resin similar to that used for the partition layer 11. Furthermore, the photosensitive resin used for top cover layer 12 is a resin having thermal fluidity. By using a photosensitive resin having thermal fluidity as the material for top cover layer 12, top cover layer 12 can be formed without using an adhesive in micro-channel chip 1. This prevents adhesive components from eluting into the channel, and suppresses reaction inhibition of the solution in the channel.
[0028] Furthermore, conventionally, bonding a partition layer and a cover member with an adhesive requires sophisticated equipment and techniques, making the manufacturing method complicated. In micro-channel chip 1 according to this embodiment, by using a resin with thermal fluidity (in this example, a photosensitive resin) as the material for upper cover layer 12, upper cover layer 12 can be formed on partition layer 11 more easily than conventionally. This makes it possible to prevent the manufacturing method from becoming too complicated.
[0029] The photosensitive resin having thermal fluidity preferably has a melt flow rate (MFR) in the range of 1 g / 10 min to 100 g / 10 min (230°C), which makes it possible to easily form upper cover layer 12 in the manufacturing process described below.
[0030] As will be described in more detail below, upper cover layer 12 is formed by causing a photosensitive resin having thermal fluidity formed on partition layer 11 to flow (reflow) onto flow path section 3 by heat treatment. Therefore, as shown in FIG. 2, upper cover layer 12 has recessed section 120. In other words, upper cover layer 12 has a recessed region. Specifically, the thickness of upper cover layer 12 becomes thinner from the partition layer 11 side toward the center of flow path section 3, thereby forming recessed section 120 in a cross-sectional view.
[0031] Furthermore, upper lid layer 12 may be formed of a resin material having a lower glass transition temperature (Tg) than partition layer 11. For example, upper lid layer 12 may have a glass transition temperature that is 30°C to 50°C lower than that of partition layer 11. In this case, the photosensitive resin forming partition layer 11 has a higher glass transition temperature (Tg) than the photosensitive resin forming upper lid layer 12, so there is almost no resin flow. This makes it possible to prevent flow in partition layer 11 during the formation of upper lid layer 12, which would otherwise cause a change in the flow path pattern. Furthermore, the glass transition temperature (Tg) of the upper lid layer 12 is preferably within the range of 100°C or higher and 300°C or lower.
[0032] The upper cover layer 12 has an exposure sensitivity of 5 μC / cm 2 More than 50μC / cm2 It is preferable that the content is within the following range. The upper lid layer 12 may have a different exposure sensitivity from that of the partition wall layer 11. For example, the upper lid layer 12 may have a different exposure sensitivity from that of the partition wall layer 11 by 5 μC / cm 2 More than 20μC / cm 2 The exposure sensitivity may be high within the following range. For example, the upper cover layer 12 has a resistance of 5 μC / cm 2 More than 20μC / cm 2 The exposure sensitivity may be low within the following range. In this way, the upper cover layer 12 may have a higher or lower exposure sensitivity than the partition wall layer 11 .
[0033] When upper cover layer 12 has a different exposure sensitivity from partition layer 11, the opening width of the photosensitive resin that forms partition layer 11, i.e., the width of the flow path pattern, can be made sufficiently large by setting the exposure amount according to the photosensitive resin that forms partition layer 11. Therefore, even if the resin for the partition layer flows when the resin material for the upper cover layer is caused to flow during the formation of upper cover layer 12, the opening width of the photosensitive resin that forms partition layer 11 can be made sufficiently large, and sufficient space can be maintained for flow path section 3.
[0034] (1.1.4) Flow path configuration 3 is a diagram showing an example of the cross-sectional shape of the channel section 3 of the micro-channel chip 1 according to this embodiment. In this embodiment, it is preferable that the cross-sectional shape of the channel section 3 has rounded corners (for example, each side of the cross section of the channel section 3 is connected by an arc). This stabilizes the liquid transfer speed and flow rate of the fluid (for example, a reaction solution) in the channel section 3 and prevents the test substance from accumulating at the corners. Here, the cross-sectional shape of the flow path section 3 in this embodiment will be described with reference to FIG. 3. FIG. 3 is an enlarged cross-sectional schematic diagram showing a cross-section of the flow path section 3 having rounded corners. As shown in FIG. 3, the area of an imaginary cross-section A1 when the cross-sectional shape of the flow path section 3 is rectangular is different from the area of a cross-section of the flow path section 3 having rounded corners. Specifically, as shown in FIG. 3, the cross-section of the flow path section 3 has four arc-shaped corners. Therefore, the cross-section of the flow path section 3 is smaller in area than the imaginary cross-section A1 by the sum of the areas of the imaginary corners A11, A12, A13, and A14. In this embodiment, the cross section of the flow path section 3 having rounded corners may have an area of the cross section of the flow path section 3 within a range of 95% to 98% of the surface area of the imaginary cross section A1. Note that in FIG. 3, the cross section of the flow path section 3 is a rectangle with rounded corners, but this is not limited to this and may be a shape other than a rectangle (a polygon with rounded corners). In this case, too, it is sufficient that the area of the cross section of the flow path section 3 is within a range of 95% to 98% of the surface area of the imaginary cross section when the corners are not rounded.
[0035] The ten-point surface roughness Rz of the flow path section 3 is preferably in the range of 0.001 μm to 0.03 μm. Here, the ten-point surface roughness Rz of the flow path section 3 indicates the roughness of the side surface of the partition layer 11 on the flow path section 3 side and the surface of the substrate 10 on the flow path section 3 side. By appropriately designing the ten-point surface roughness Rz within the above-mentioned range, it is possible to perform an inspection according to the reaction solution, the test object, and the desired test conditions. For example, when the surface roughness Rz of the flow path section 3 is in the range of 0.001 μm or more and 0.01 μm or less, contact between the fluid (e.g., reaction solution) or the test object introduced into the flow path section 3 and the inner surface of the flow path section 3 can be reduced, thereby improving the liquid transport properties (e.g., liquid transport speed and flow rate).
[0036] Furthermore, when the surface roughness Rz is in the range of greater than 0.02 μm and not more than 0.03 μm, the liquid delivery speed can be reduced to ensure the time that the fluid or test substance introduced into the flow path section 3 remains within the flow path section 3, i.e., the reaction time. Furthermore, when the surface roughness Rz is in the range of more than 0.01 μm and not more than 0.02 μm, both an appropriate liquid transfer speed and sufficient reaction time for the fluid and test substance in the channel section 3 can be ensured. Furthermore, the surface roughness of the channel section 3 can be appropriately controlled during the production of the micro-channel chip 1 by a known etching method or the like.
[0037] (1.2) Manufacturing method of microfluidic chip Next, a method for manufacturing the micro-channel chip 1 according to this embodiment will be described. Fig. 4 is a flowchart showing an example of a method for manufacturing the micro-channel chip 1 according to this embodiment. Here, an example in which the partition wall layer 11 is formed from a photosensitive resin will be described.
[0038] (Step S1) In the method for manufacturing the micro-channel chip 1 according to this embodiment, first, a step is performed in which a partition resin (an example of a first photosensitive resin) for forming the partition layer 11 is applied onto the substrate 10. This provides a resin layer for forming the partition layer 11 on the substrate 10. In the method for manufacturing the micro-channel chip 1 according to this embodiment, for example, a resin layer (first photosensitive resin layer) made of a photosensitive resin is formed on the substrate 10.
[0039] The photosensitive resin layer is formed on the substrate 10, for example, by coating the substrate 10 with a photosensitive resin. Coating can be performed by, for example, spin coating, spray coating, bar coating, etc., with spin coating being preferred from the viewpoint of film thickness controllability. The photosensitive resin can be coated on the substrate 10 in various forms, such as liquid, solid, gel, or film. Of these, it is preferable to form the photosensitive resin layer using a liquid resist. The liquid resist may be either a positive or negative resist, as appropriate, depending on the characteristics of the flow path pattern. Furthermore, a resin (for example, a photosensitive resin) may be applied onto the substrate 10 so that the thickness of the resin layer (for example, a photosensitive resin layer), that is, the thickness of the partition wall layer 11, is within the range of 1 μm to 500 μm.
[0040] (Step S2) Once the first photosensitive resin layer made of a partition resin has been formed on the substrate 10, a heating process (pre-baking process) is then carried out to remove the solvent contained in the resin (e.g., photosensitive resin) applied to the substrate 10. Note that in the method for manufacturing the micro-channel chip 1 according to this embodiment, the pre-baking process is not an essential process and may be carried out under optimal conditions (temperature, time) according to the properties of the resin. For example, if the resin layer on the substrate 10 is a photosensitive resin, the pre-baking temperature and time are appropriately set under optimal conditions according to the properties of the photosensitive resin. To improve adhesion between the substrate and the photosensitive resin, the substrate may be subjected to HMDS treatment or coated with a thin film of resin, as necessary.
[0041] (Step S3) Next, a step is performed in which a top cover resin (an example of a second photosensitive resin) is applied onto the first photosensitive resin layer to form top cover layer 12. This provides a resin layer for forming top cover layer 12 on the pre-baked partition resin. In the method for manufacturing microchannel chip 1 according to this embodiment, a resin layer (second photosensitive resin layer) made of a photosensitive resin having thermal fluidity is formed on substrate 10, for example. The method for forming the second photosensitive resin layer on substrate 10 can be the same as the method for forming the first photosensitive resin layer in step S1 above.
[0042] (Step S4) Next, a second photosensitive resin layer made of a resin for forming the top cover is formed on the first photosensitive resin layer made of a resin for forming the partition wall. A heat treatment (pre-baking) is then performed to remove the solvent contained in the resin for forming the top cover applied to the first photosensitive resin layer. The pre-baking process in this step is not essential, and similar to the pre-baking process in step S2, it may be performed under optimal conditions (temperature, time) according to the resin characteristics. Furthermore, to improve the adhesion between the first and second photosensitive resin layers, the substrate may be subjected to an HMDS treatment or coated with a thin film of resin, if necessary. This results in two photosensitive resin layers being formed on the substrate 10.
[0043] As shown in steps S1 to S4 above, the two photosensitive resin layers (first photosensitive resin layer and second photosensitive resin layer) for forming partition layer 11 and top cover layer 12 are welded together without using any adhesive. That is, in micro-channel chip 1 according to this embodiment, partition layer 11 and top cover layer 12 are welded together. That is, in micro-channel chip 1 according to this embodiment, partition layer 11 and top cover layer 12 can be joined together without using an intermediate member (for example, an adhesive). This prevents adhesive components from leaking into channel section 3 and also prevents poor joining due to uneven adhesive film thickness. In this embodiment, the photosensitive resin has two layers, but is not limited to this and may have three or more layers.
[0044] (Step S5) Next, a step of exposing the resin (e.g., first photosensitive resin layer, second photosensitive resin layer) coated on substrate 10 is carried out. Specifically, a flow path pattern is written on the photosensitive resin coated on substrate 10 by exposure. Exposure can be carried out, for example, by an exposure device using ultraviolet light as a light source or a laser writing device. Among these, exposure using a proximity exposure device or a contact exposure device using ultraviolet light as a light source is preferred. In the case of a proximity exposure device, exposure is carried out through a photomask having the flow path pattern arrangement of micro-channel chip 1. The photomask may be a photomask having a light-shielding film with a two-layer structure of chromium and chromium oxide.
[0045] When the photosensitive resin (first photosensitive resin layer, second photosensitive resin layer) coated on substrate 10 is a positive resist, the exposed region dissolves to form channel section 3, and the photosensitive resin remaining in the unexposed region becomes partition layer 11 and upper cover layer 12. When the photosensitive resin coated on substrate 10 is a negative resist, the photosensitive resin remaining in the exposed region becomes partition layer 11 and upper cover layer 12, and the unexposed region dissolves to form channel section 3. In this way, in the method for manufacturing micro-channel chip 1 according to this embodiment, partition layer 11 that constitutes channel section 3 can be formed on substrate 10 using photolithography.
[0046] When a chemically amplified resist or the like is used to form the resin layer on the substrate 10, it is advisable to further perform a heat treatment (post-exposure bake: PEB) after exposure in order to promote the catalytic reaction of the acid generated by exposure.
[0047] (Step S6) Next, the exposed photosensitive resin is developed to form a flow path pattern. Development is carried out by reacting the photosensitive resin with a developer in a developing device such as a spray, dip, or paddle type. Examples of the developer that can be used include aqueous sodium carbonate solution, tetramethylammonium hydroxide, potassium hydroxide, and organic solvents. The developer may be an optimum solution suited to the properties of the photosensitive resin, and is not limited to these. The concentration and development time can be adjusted to the optimum conditions suited to the properties of the photosensitive resin.
[0048] (Step S7) Next, a process is performed in which the developer used for development is completely removed from the resin layer (photosensitive resin layer) on the substrate 10 by washing. Washing can be performed using a washing device such as a spray, shower, or immersion type. As the washing water, for example, pure water, isopropyl alcohol, or the like, may be used as appropriate, as the most suitable washing water for removing the developer used in the development process. After washing, the substrate is dried using a spin dryer, an IPA vapor dryer, natural drying, or the like. Even at this stage, the second photosensitive resin layer made of the upper cover resin remains on the partition wall layer 11.
[0049] (Step S8) Next, a heat treatment (post-baking) is performed on the partition layer 11 and the second photosensitive resin layer that form the flow path pattern, i.e., the flow path section 3. This post-baking process removes any moisture remaining from development and cleaning. This post-baking process also forms the upper cover layer 12 that serves as a lid for the flow path section 3 and defines the upper portion of the flow path section 3. Specifically, this post-baking process promotes the flow (reflow) of the upper cover resin, which is a fluid photosensitive resin, to form the upper cover layer 12 of the flow path section 3. The temperature and time of the post-baking are optimized to suit the characteristics of the upper cover resin. As shown in FIG. 1, the upper cover layer 12 is a lid material that covers the flow path section 3 and is formed on the flow path section 3. The input section 2 and the output section 4 are open and not covered by the upper cover layer 12. The post-baking process is performed using, for example, a hot plate, an oven, or the like. If the drying in the cleaning process of step S7 is insufficient, the developer or moisture from the cleaning process may remain in the partition layer 11. Also, solvent that was not removed in the pre-baking process may remain in the partition layer 11. These can be removed by performing the post-baking process.
[0050] As described above, the manufacturing method of the microchannel chip 1 according to this embodiment includes the steps of applying a partition resin onto the substrate 10 (step S1 above), applying a top cover resin onto the applied partition resin (step S3 above), exposing the partition resin and the top cover resin to light (step S5 above), developing and washing the exposed partition resin and top cover resin to form a partition layer 11 that defines the channel section 3 on the substrate 10 (steps S6 and S7 above), and heating the top cover resin on the partition layer 11 to cause the top cover resin to flow and form the top cover layer 12 of the channel section 3 (step S8 above). This allows the partition layer 11 and the upper cover layer 12 to be welded together without using an adhesive, preventing the adhesive components from leaching into the flow path section 3 and suppressing reaction inhibition of the solution in the flow path.
[0051] (1.3) Details of the manufacturing process of the barrier layer and the upper cover layer In the method for manufacturing micro-channel chip 1 according to this embodiment, each manufacturing step is adjusted depending on the physical properties of the partition resin for forming partition layer 11 and the top cover resin for forming top cover layer 12. Specific examples will be described below. (1.3.1) Formation of partition layer and upper cover layer using resins with different glass transition temperatures The formation of partition layer 11 and upper cover layer 12 when the glass transition temperatures of the partition resin and the upper cover resin are different will be described with reference to Fig. 5. Fig. 5(a) is a cross-sectional view showing first photosensitive resin layer 41 and second photosensitive resin layer 42 formed on substrate 40, Fig. 5(b) is a cross-sectional view showing the flow channel pattern on substrate 40, and Fig. 5(c) is a cross-sectional view showing the general configuration of micro-channel chip 400 according to this example. In this example, we will explain a method for manufacturing a microchannel chip under the condition that the glass transition temperature (Tg) of the resin for the top cover is lower than the glass transition temperature (Tg) of the resin for the partition wall (glass transition temperature (Tg) of the resin for the top cover < glass transition temperature (Tg) of the resin for the partition wall).
[0052] As shown in FIG. 5(a), in this example, in the coating process of step S1, a photosensitive resin for partition walls is applied onto the substrate 40 to form a first photosensitive resin layer 41. The photosensitive resin for partition walls is applied to the substrate 40 in a desired thickness by, for example, spin coating. Also, in this example, in step S3, a photosensitive resin for top cover is applied onto the first photosensitive resin layer 41 to form a second photosensitive resin layer 42. In this example, the photosensitive resin for top cover that forms the second photosensitive resin layer 42 is a resin that has a lower glass transition temperature (Tg) than the photosensitive resin for partition walls that forms the first photosensitive resin layer 41. The second photosensitive resin layer 42 is applied onto the first photosensitive resin layer 41 in a desired thickness by spin coating, similar to the first photosensitive resin layer 41.
[0053] In this example, in the exposure step of step S5, a flow path pattern is written on the first photosensitive resin layer 41 and the second photosensitive resin layer 42 coated on the substrate 40 via a photomask. For example, in this example, a proximity exposure device using light in the ultraviolet region with a wavelength of 350 nm to 400 nm as a light source is used. Next, in the development step of step S6, the exposed first photosensitive resin layer 41 and the second photosensitive resin layer 42 are developed to form the flow path pattern 43. Here, for example, a sodium carbonate aqueous solution is used as the developer by a spray method. Next, in step S7, the developed first photosensitive resin layer 41 and the second photosensitive resin layer 42 are washed to completely remove the developer. Here, for example, ultrapure water is used by a spray method. As a result, a partition layer 41a is formed as shown in FIG. 5(b), and the flow path pattern 43 is defined.
[0054] Next, the micro-channel chip with flow channel pattern 43 formed thereon is subjected to a heat treatment (post-bake) in step S8. In this example, the heat treatment is performed using a hot plate at a temperature near the glass transition temperature (Tg) of second photosensitive resin layer 42. In this example, the heat treatment promotes the flow (reflow) of second photosensitive resin layer 42, i.e., the upper-cover resin, and the upper-cover resin flows from above opposing left and right partition layers 11 toward the center of flow channel pattern 43. The upper-cover resin that has flowed from above partition layer 41a is bonded to the opposite side of substrate 40, i.e., the upper side of flow channel pattern 43, to form upper-cover layer 42a. As a result, as shown in FIG. 5(c), the top of flow channel pattern 43 is covered with upper-cover layer 42a, forming flow channel portion 43a and completing micro-channel chip 400.
[0055] In this example, when the glass transition temperature (Tg) of first photosensitive resin layer 41 forming partition layer 41a, i.e., the partition resin, is higher than the glass transition temperature (Tg) of second photosensitive resin layer 42, i.e., the top cover resin, there is almost no flow of the partition resin even when the top cover resin reflows due to heat treatment. Therefore, by satisfying the condition "glass transition temperature (Tg) of top cover resin < glass transition temperature (Tg) of partition resin," the top cover resin can be caused to flow and top cover layer 42a can be easily formed without causing deformation of the flow path pattern due to the flow of the top cover resin.
[0056] (1.3.2) Formation of a partition layer and an upper cover layer using resins with different exposure sensitivities (1) The formation of partition layer 11 and upper cover layer 12 when the exposure sensitivity of the partition resin and the upper cover resin differ will be described with reference to Fig. 6. Fig. 6(a) is a cross-sectional view showing first photosensitive resin layer 51 and second photosensitive resin layer 52 formed on substrate 50, Fig. 6(b) is a cross-sectional view showing the flow channel pattern on substrate 50, and Fig. 6(c) is a cross-sectional view showing the general configuration of micro-channel chip 500 according to this example. In this example, the exposure sensitivity (C / cm 2 ) is the exposure sensitivity of the partition wall resin (C / cm 2 ) (the exposure sensitivity of the resin for the lid (C / cm 2 )<Exposure sensitivity of partition wall resin (C / cm 2 A method for manufacturing a microchannel chip under the conditions above will be described.
[0057] As shown in FIG. 6(a), in this example, in the coating process of step S1, a photosensitive resin for partition walls is applied onto the substrate 50 to form a first photosensitive resin layer 51. The photosensitive resin for partition walls is applied to the substrate 50 to a desired thickness by, for example, spin coating. The first photosensitive resin layer 51, i.e., the resin for partition walls, is a positive resist. Also, in this example, in step S3, a photosensitive resin for top cover is applied onto the first photosensitive resin layer 51 to form a second photosensitive resin layer 52. The second photosensitive resin layer 52, i.e., the resin for top cover, is a positive resist. That is, in this example, positive resists are used as the photosensitive resin for partition walls and the photosensitive resin for top cover. In this example, the photosensitive resin for the upper cover forming the second photosensitive resin layer 52 has a higher exposure sensitivity (C / cm ) than the photosensitive resin for the partition walls forming the first photosensitive resin layer 51. 2 ) is used. The second photosensitive resin layer 52 is applied to a desired thickness on the first photosensitive resin layer 51 by spin coating, similar to the first photosensitive resin layer 51. For example, a chemically amplified resist may be used as the partition resin that forms the first photosensitive resin layer 51, and a non-chemically amplified resist may be used as the top cover resin that forms the second photosensitive resin layer 52.
[0058] In this example, in the exposure process of step S5, a flow path pattern is written via a photomask on the first photosensitive resin layer 51 and the second photosensitive resin layer 52 coated on the substrate 50. For example, in this example, a proximity exposure device is used that uses light in the ultraviolet region with a wavelength of 350 nm or more and 400 nm or less as a light source. Here, the exposure amount is set to an optimum exposure amount for the first photosensitive resin layer 51. As described above, in this example, the top cover resin that forms the second photosensitive resin layer 52 has lower exposure sensitivity than the partition wall resin that forms the first photosensitive resin layer 51. Therefore, although the reaction is insufficient in the second photosensitive resin layer 52 with an exposure amount that matches the exposure amount for the first photosensitive resin layer 51, this does not cause any problems in terms of pattern resolution. Next, in the development step of step S6, the exposed first photosensitive resin layer 51 and second photosensitive resin layer 52 are developed to form a flow path pattern 53. Here, for example, a sodium carbonate aqueous solution is used as the developer by a spray method. Next, the first photosensitive resin layer 51 and second photosensitive resin layer 52 developed in step S7 are washed to completely remove the developer. Here, for example, ultrapure water is used by a spray method. As a result, a partition layer 51a is formed as shown in FIG. 6(b), and the flow path pattern 53 is defined. In this example, as described above, the second photosensitive resin layer 52 is formed of a resin having lower exposure sensitivity than the first photosensitive resin layer 51. Therefore, as shown in FIG. 6, the opening width of the exposed area in the second photosensitive resin layer 52 is smaller than the opening width in the first photosensitive resin layer 51.
[0059] Next, the micro-channel chip with the flow channel pattern 53 formed thereon is subjected to a heat treatment (post-baking) in step S8. In this example, the heat treatment is performed using a hot plate at a temperature near the glass transition temperature (Tg) of the first photosensitive resin layer 51 and the second photosensitive resin layer 52. In this example, the heat treatment promotes the flow (reflow) of the second photosensitive resin layer 52, i.e., the upper-cover resin, and the upper-cover resin flows from the left and right partition layers 51a toward the center of the flow channel pattern 53. The upper-cover resin that has flowed from the partition layer 51a is bonded to the opposite side of the substrate 50, i.e., the upper side of the flow channel pattern 53, to form the upper-cover layer 52a. As a result, as shown in FIG. 6(c), the upper part of the flow channel pattern 53 is covered with the upper-cover layer 52a, forming a flow channel portion 53a, and the micro-channel chip 500 is fabricated.
[0060] In this example, the glass transition temperature (Tg) of the first photosensitive resin layer 51 forming the partition layer 51a, i.e., the partition resin, is equal to the glass transition temperature (Tg) of the second photosensitive resin layer 52 forming the top cover layer 52a, i.e., the top cover resin. Therefore, when the top cover resin flows (reflows), the partition resin also flows. However, in this example, the first photosensitive resin layer 51 and the second photosensitive resin layer 52 are formed of a positive resist, and the exposure sensitivity of the second photosensitive resin layer 52 is lower than that of the first photosensitive resin layer 51. Therefore, as shown in FIG. 6(b), the opening width of the second photosensitive resin layer 52 is smaller than that of the first photosensitive resin layer 51, and the opening width of the first photosensitive resin layer 51 is sufficiently larger than that of the second photosensitive resin layer 52. Therefore, although the width of the flow path portion 53a is reduced compared to the opening width of the flow path pattern 53 due to the occurrence of flow in the first photosensitive resin layer 51 to the same extent as in the second photosensitive resin layer 52, the width of the flow path portion 53a is sufficiently secured as shown in FIG. 6(c).
[0061] Therefore, by forming the first photosensitive resin layer 51 and the second photosensitive resin layer 52 using a positive resist and satisfying the condition that "the exposure sensitivity of the resin for the top cover < the exposure sensitivity of the resin for the partition wall," the resin for the top cover and the resin for the partition wall can be caused to flow to easily form the top cover layer 52a while sufficiently maintaining the flow path width of the flow path section.
[0062] (1.3.3) Formation of a partition layer and an upper cover layer using resins with different exposure sensitivities (2) The formation of partition layer 11 and upper cover layer 12 when the exposure sensitivity of the partition resin and the upper cover resin differ will be described with reference to Fig. 7. Fig. 7(a) is a cross-sectional view showing first photosensitive resin layer 61 and second photosensitive resin layer 62 formed on substrate 60, Fig. 7(b) is a cross-sectional view showing the flow channel pattern on substrate 60, and Fig. 7(c) is a cross-sectional view showing the general configuration of micro-channel chip 600 according to this example. In this example, the exposure sensitivity (C / cm 2 ) is the exposure sensitivity of the partition wall resin (C / cm 2 ) (exposure sensitivity of the resin for the lid (C / cm 2)>Exposure sensitivity of partition wall resin (C / cm 2 A method for manufacturing a microchannel chip under the conditions above will be described.
[0063] As shown in FIG. 7(a), in this example, in the coating process of step S1, a photosensitive resin for partition walls is applied onto a substrate 60 to form a first photosensitive resin layer 61. The photosensitive resin for partition walls is applied to the substrate 60 to a desired thickness by, for example, spin coating. The first photosensitive resin layer 61, i.e., the resin for partition walls, is a negative resist. Also, in this example, in step S3, a photosensitive resin for top cover is applied onto the first photosensitive resin layer 61 to form a second photosensitive resin layer 62. The second photosensitive resin layer 62, i.e., the resin for top cover, is a negative resist. That is, in this example, negative resists are used as the photosensitive resin for partition walls and the photosensitive resin for top cover. In this example, the photosensitive resin for the upper cover forming the second photosensitive resin layer 52 has a higher exposure sensitivity (C / cm ) than the photosensitive resin for the partition walls forming the first photosensitive resin layer 51. 2 ) is used. The second photosensitive resin layer 52 is applied to a desired thickness on the first photosensitive resin layer 51 by spin coating, similar to the first photosensitive resin layer 51. For example, a non-chemically amplified resist may be used as the partition resin for forming the first photosensitive resin layer 61, and a chemically amplified resist may be used as the top cover resin for forming the second photosensitive resin layer 62.
[0064] In this example, in the exposure process of step S5, a flow path pattern is written via a photomask on the first photosensitive resin layer 61 and the second photosensitive resin layer 62 coated on the substrate 60. For example, in this example, a proximity exposure device is used that uses light in the ultraviolet region with a wavelength of 350 nm or more and 400 nm or less as a light source. Here, the exposure amount is set to an optimum exposure amount for the first photosensitive resin layer 61. As described above, in this example, the upper cover resin that forms the second photosensitive resin layer 62 has a higher exposure sensitivity than the partition wall resin that forms the first photosensitive resin layer 61. Therefore, the exposure amount for the second photosensitive resin layer 62 that matches that for the first photosensitive resin layer 61 is necessary and sufficient. Next, in the development process of step S6, the exposed first photosensitive resin layer 61 and second photosensitive resin layer 62 are developed to form a flow path pattern 63. Here, for example, a sodium carbonate aqueous solution is used as the developer by a spray method. Next, the first photosensitive resin layer 61 and second photosensitive resin layer 62 developed in step S7 are washed to completely remove the developer. Here, for example, ultrapure water is used by a spray method. As a result, as shown in FIG. 7(b), a partition layer 61a is formed and the flow path pattern 63 is defined. In this example, the second photosensitive resin layer 62 has a higher exposure sensitivity than the first photosensitive resin layer 61. Therefore, as shown in FIG. 7(b), after exposure, the area of the second photosensitive resin layer 62 remaining as the exposed portion pattern is wider than the first photosensitive resin layer 61. As a result, as shown in FIG. 6, the opening width of the exposed area in the second photosensitive resin layer 62 is smaller than the opening width in the first photosensitive resin layer 61.
[0065] Next, the micro-channel chip with the flow channel pattern 63 formed thereon is subjected to a heat treatment (post-baking) in step S8. In this example, the heat treatment is performed using a hot plate at a temperature near the glass transition temperature (Tg) of the first photosensitive resin layer 61 and the second photosensitive resin layer 62. In this example, the heat treatment promotes the flow (reflow) of the second photosensitive resin layer 62, i.e., the upper-cover resin, and the upper-cover resin flows from the left and right partition layers 61a toward the center of the flow channel pattern 63. The upper-cover resin that has flowed from the partition layer 61a is bonded to the opposite side of the substrate 60, i.e., the upper side of the flow channel pattern 63, to form the upper-cover layer 62a. As a result, as shown in FIG. 7(c), the upper part of the flow channel pattern 63 is covered with the upper-cover layer 62a, forming a flow channel portion 63a, and the micro-channel chip 600 is fabricated.
[0066] In this example, similar to the micro-channel chip 500 described above, in the micro-channel chip 600, the glass transition temperature (Tg) of the first photosensitive resin layer 61 forming the partition layer 61a, i.e., the partition resin, is equal to the glass transition temperature (Tg) of the second photosensitive resin layer 62 forming the top cover layer 62a, i.e., the top cover resin. Therefore, when the top cover resin flows (reflows), the partition resin also flows. In this example, the first photosensitive resin layer 61 and the second photosensitive resin layer 62 are formed of a negative resist, and the exposure sensitivity of the second photosensitive resin layer 62 is higher than that of the first photosensitive resin layer 61. Therefore, as shown in FIG. 6(b), the opening width of the second photosensitive resin layer 62 is smaller than that of the first photosensitive resin layer 61, and the opening width of the first photosensitive resin layer 61 is sufficiently larger than that of the second photosensitive resin layer 52. Therefore, although the width of the flow path portion 63a is reduced compared to the opening width of the flow path pattern 63 due to the occurrence of flow in the first photosensitive resin layer 61 to the same extent as in the second photosensitive resin layer 62, the width of the flow path portion 63a is sufficiently secured as shown in FIG. 7(c).
[0067] Therefore, by forming the first photosensitive resin layer 61 and the second photosensitive resin layer 62 using a negative resist and satisfying the condition that "the exposure sensitivity of the resin for the top cover is greater than the exposure sensitivity of the resin for the partition wall," the resin for the top cover and the resin for the partition wall can be caused to flow to easily form the top cover layer 62a while adequately maintaining the flow path width of the flow path section.
[0068] The above describes an example of a microchannel chip according to this embodiment in which the partition layer and the upper cover layer are formed separately (multi-layer structure). As described above, according to the manufacturing method according to this embodiment, the cover material (upper cover layer) covering the channel portion of the microchannel chip can be formed within the scope of an existing photolithography process without using an intermediate layer such as an adhesive. This prevents the adhesive components from eluting into the channel and suppresses reaction inhibition of the solution in the channel. Furthermore, it is possible to prevent quality degradation due to poor bonding caused by uneven adhesive film thickness, and the manufacturing method can be simplified compared to when bonding the partition wall layer and the upper cover layer using an intermediate member such as an adhesive.
[0069] However, the present disclosure is not limited thereto, and the partition layer and the upper cover layer may be composed of three or more layers. In this case, the second photosensitive resin layer forming the upper cover layer may have a multi-layer structure. Photosensitive resins with thermal fluidity have the property that the fluidity of the resin increases with heat treatment, the higher the layer. Therefore, when the upper cover layer is formed using a multi-layer second photosensitive resin layer, the upper layer portions bond faster than the lower layer portions. Therefore, the upper layer of the upper cover layer made of a multi-layer second photosensitive resin layer has a narrower opening width, and the upper layer or a layer adjacent to the top layer is bonded.
[0070] (1.4) Effects of the First Embodiment The micro-channel chip 1 described above has the following effects. (1) The microchannel chip 1 of this embodiment comprises a substrate 10, a partition layer 11 that forms a channel section 3 on the substrate 10, and an upper cover layer 12 that is formed on the surface of the partition layer 11 opposite the substrate 10 and serves as a lid for the channel section 3, and no adhesive layer is provided between the partition layer 11 and the upper cover layer 12. This prevents the adhesive components from eluting into the channels and inhibits reaction of the solution in the channels, and also prevents poor bonding due to uneven adhesive film thickness. (2) The microchannel chip 1 according to this embodiment also comprises a substrate 10, a partition layer 11 that forms a channel section 3 on the substrate 10, and an upper cover layer 12 that is formed on the surface of the partition layer 11 opposite the substrate 10 and serves as a lid for the channel section 3, and the upper cover layer 12 and the partition layer 11 are welded to each other. As a result, in micro-channel chip 1, upper cover layer 12 and partition layer 11 are bonded together without using an adhesive, preventing adhesive components from eluting into the channel and suppressing reaction inhibition of the solution in the channel. Furthermore, bonding defects due to uneven adhesive film thickness can also be prevented. (3) Furthermore, the microchannel chip 1 according to this embodiment is a microchannel chip that includes a channel section 3 and an upper cover layer 12 that serves as a lid for the channel section 3. The upper cover layer 12 is made of a resin having thermal fluidity, and the cross-sectional shape of the channel section 3 has rounded corners. As a result, in micro-channel chip 1, upper cover layer 12 and partition layer 11 are bonded together without using an adhesive, preventing adhesive components from eluting into the channel and suppressing reaction inhibition of the solution in the channel. Furthermore, the liquid transfer speed and flow rate of the fluid (e.g., reaction solution) in channel section 3 can be stabilized, and retention of the test substance at corners can be suppressed. Furthermore, upper cover layer 12 and partition layer 11 can be bonded together within the scope of existing photolithography processes.
[0071] (4) In the micro-channel chip 1 according to this embodiment, the upper cover layer 12 may be a separate body from the partition layer 11. This allows for the appropriate selection of a resin having suitable properties for the top cover. (5) In addition, in the microchannel chip 1 according to this embodiment, the partition layer 11 and the upper cover layer 12 are formed of a resin material, and the resin material may be a photosensitive resin that is sensitive to light having a wavelength of 190 nm or more and 400 nm or less, which is in the ultraviolet light region. This allows the lid material (upper lid layer) of the microchannel chip to be formed by reflowing the photosensitive resin without using an adhesive, preventing the adhesive components from leaching into the channel and suppressing reaction inhibition of the solution in the channel. (6) In the micro-channel chip 1 according to this embodiment, the upper cover layer 12 may be separate from the partition layer 11 and may have a lower glass transition temperature than the partition layer 11. This makes it possible to prevent flow from occurring in partition layer 11 during the formation of upper cover layer 12, thereby preventing the flow path pattern from changing. (7) In the micro-channel chip 1 according to this embodiment, the upper cover layer 12 may be separate from the partition layer 11 and may have a higher or lower exposure sensitivity than the partition layer 11. As a result, even if the resin for the partition layer flows when the resin material for the upper cover layer is caused to flow during the formation of the upper cover layer 12, the opening width of the photosensitive resin forming the partition layer 11 can be made sufficiently large, so that sufficient space can be maintained as the flow path section 3. (8) The manufacturing method of the microchannel chip 1 according to this embodiment includes the steps of applying a photosensitive resin for the partition layer 11 onto the substrate 10, applying a photosensitive resin for the upper cover layer 12 onto the applied photosensitive resin for the partition layer 11, exposing the photosensitive resin for the partition layer 11 and the photosensitive resin for the upper cover layer 12, developing and washing the exposed photosensitive resin for the partition layer 11 and the photosensitive resin for the upper cover layer 12 to form the partition layer 11 that defines the channel section 3 on the substrate 10, and heating the photosensitive resin for the upper cover layer 12 on the partition layer 11 to flow the photosensitive resin for the upper cover layer 12, thereby forming the upper cover layer 12 of the channel section 3. This makes it possible to provide a microchannel chip that can prevent the adhesive component from eluting into the channel and suppresses reaction inhibition of the solution in the channel.
[0072] 2. Second embodiment A micro-channel chip according to a second embodiment of the present disclosure will now be described with reference to Fig. 8. Fig. 8 is a cross-sectional view illustrating an example of a configuration of micro-channel chip 200 according to the second embodiment of the present disclosure. Micro-channel chip 200 includes substrate 20, partition layer 21 that forms channel section 23 on substrate 20, and upper cover layer 22 that is formed from part of partition layer 21. That is, micro-channel chip 200 has partition layer 21 and upper cover layer 22 that are integrated together. In this respect, micro-channel chip 200 differs from micro-channel chips 1, 400, 500, and 600 according to the first embodiment.
[0073] (2.1) Configuration of the microchannel chip 200 The following description will focus on the differences between partition layer 21 and upper cover layer 22 of micro-channel chip 200 and partition layer 11 and upper cover layer 12 of the first embodiment. Note that the components other than upper cover layer 22 (substrate 20 and channel section 23) are similar to those of substrate 10 and channel section 3 of micro-channel chip 1, and therefore will not be repeated. Furthermore, the materials for partition layer 21 and upper cover layer 22 of micro-channel chip 200 may be the same as those for partition layer 11 of micro-channel chip 1.
[0074] 8 shows an example of the configuration of micro-channel chip 200 in which partition layer 21 and upper cover layer 22 are integrated. In micro-channel chip 200, partition layer 21 itself serves as upper cover layer 22, which simplifies the manufacturing process.
[0075] (2.2) Manufacturing Method of Microchannel Chip 200 An example of a method for manufacturing the micro-channel chip 200 will now be described. In the method for manufacturing micro-channel chip 200, step S3 (the step of applying the second photosensitive resin) in the method for manufacturing micro-channel chip 1 shown in Fig. 4 can be omitted, thereby simplifying the manufacturing process. Hereinafter, the method for manufacturing the micro-channel chip 200 will be described in more detail with reference to FIG.
[0076] 9 is a schematic diagram showing each step of the method for manufacturing micro-channel chip 200 according to this embodiment. In the method for manufacturing micro-channel chip 200, a channel pattern is formed in the same manner as in steps S1, S2, and S4 to S7 in the method for manufacturing micro-channel chip 1 shown in FIG. 4, except that only one layer of photosensitive resin is formed on substrate 20. Therefore, a description of each step of steps S1, S2, and S4 to S7 will be omitted.
[0077] 9(a) is a schematic plan view of a channel pattern 220 during the manufacture of a micro-channel chip 200 according to this embodiment. The channel pattern 220 has an input section 32 for introducing a liquid into the partition layer 21, a channel section 33 through which the liquid flows, and an output section 34 for discharging the liquid. The input section 32 and the output section 34 have the same configuration as the input section 2 and the output section 4 of the micro-channel chip 1 according to the first embodiment, and therefore a description thereof will be omitted. Figure 9(b) is a cross-sectional view taken along line BB in Figure 9(a). A partition wall layer 21 is formed on a base substrate 20. An input section 32 for introducing a fluid (e.g., a reaction solution) is formed in the area surrounded by the substrate 20 and the partition wall layer 21. Note that, in order to introduce a fluid, an upper lid layer 22 is not formed on the top of the input section 32.
[0078] Fig. 9(c) is a cross-sectional view taken along line CC in Fig. 9(a). A partition layer 21 is formed on a substrate 20 serving as a base member, and a region 23a of a flow path pattern 220 that defines a flow path section 3 through which a fluid flows is formed in an area surrounded by the substrate 20 and the partition layer 21. The opening width of region 23a is formed narrower than that of input section 32.
[0079] The formed flow channel pattern 220 is subjected to a heat treatment (post-baking). The heat treatment can be performed using, for example, a hot plate or an oven. The post-baking is performed to heat the partition resin (partition layer 21) to the glass transition temperature (Tg) to cause the partition resin to flow (reflow). This differs from the heat treatment in the manufacturing method of the micro-channel chip 1 according to the first embodiment. Depending on the properties of the resin, the flow (reflow) of the photosensitive resin is characterized in that the side opposite to the substrate 20, i.e., the upper side of the flow channel pattern 220, tends to flow. As the upper part of the flow channel pattern 220 flows, the partition layers 21 bond together and function as an upper cover material for the flow channel pattern 220, i.e., the upper cover layer 22 covering the region 23a of the flow channel pattern 220. As a result, the upper cover layer 22 is formed integrally with the partition layer 21, and the micro-channel chip 200 according to this embodiment is fabricated.
[0080] FIG. 9(d) is a schematic plan view of the micro-channel chip 200 after heat treatment (post-baking). The heat treatment causes the partition layer 21 to flow, forming the upper cover layer 22, and the channel section 23 is defined as shown in FIG. 9(f), which will be described later. Although not shown in FIG. 9(d), the channel section 23 can be seen through the transparent upper cover layer 22. Although the input section 32 and the output section 34 also become smaller in size as the partition layer 21 flows, they are formed large in advance in anticipation of size reduction, and therefore the through-holes remain formed without being blocked by the upper cover layer 22. This is also the case when manufacturing the micro-channel chip 1 according to the first embodiment.
[0081] 9(e) is a schematic cross-sectional view of the microchannel chip 200 taken along line BB in FIG. 9(d). Post-baking on the hot plate 25 causes the resin on the upper side of the partition layer 21 to flow toward the center of the width of the input section 32, but the input section 32 is not blocked and its open end remains in communication with the outside. In other words, the function of the input section 32 for introducing a fluid is maintained.
[0082] 9(f) is a schematic cross-sectional view of micro-channel chip 200 taken along line CC in FIG. 9(d). Post-baking on hot plate 25 causes the resin on the side of partition layer 21 opposite substrate 20 (the upper side of partition layer 21) to flow from the left and right and bond near the center of channel section 23 in the width direction, forming upper cover layer 22. As described above, according to this embodiment, the cover material (upper cover layer) for covering the channel section of the micro-channel chip can be formed within the scope of existing photolithography processes without using an adhesive. This prevents adhesive components from eluting into the channel and suppresses reaction inhibition of the solution in the channel. Furthermore, quality degradation due to poor bonding caused by uneven adhesive film thickness can be prevented. Furthermore, the manufacturing method can be simplified compared to when the partition wall layer and the upper lid layer are bonded using an intermediate member such as an adhesive. Furthermore, by integrally forming the partition wall layer 21 and the upper lid layer 22, poor bonding can be more reliably prevented.
[0083] As described above, the manufacturing method of the microchannel chip 200 according to this embodiment includes the steps of applying a partition resin onto the substrate 10 (step S1 above), exposing the partition resin to light (step S5 above), developing and washing the exposed partition resin to form a partition layer 21 that defines the channel section 23 on the substrate 20 (steps S6 and S7 above), and heating the partition layer 21 to cause the partition resin to flow and form the upper cover layer 22. This makes it possible to form the upper cover layer 22, which is integrally formed by welding to the partition layer 21 as part of the partition layer 21 without using adhesive, thereby preventing the adhesive components from leaching into the flow path portion 23 and suppressing reaction inhibition of the solution in the flow path.
[0084] (2.3) Effects of the Second Embodiment The micro-channel chip 200 described above has the following effects. (1) The micro-channel chip 200 according to this embodiment may be integrated with the partition layer 21. This makes it possible to more reliably prevent poor bonding between partition layer 21 and upper lid layer 22. (2) Furthermore, the manufacturing method of the microchannel chip 200 according to this embodiment includes the steps of applying a partition resin onto the substrate 10 (step S1 above), exposing the partition resin to light, developing and washing the exposed partition resin to form a partition layer 21 that defines the channel section 23 on the substrate 20, and heat-treating the partition layer 21 to cause the partition resin to flow and form the upper cover layer 22. This makes it possible to form the upper cover layer 22, which is integrally formed by welding to the partition layer 21 as part of the partition layer 21 without using adhesive, thereby preventing the adhesive components from leaching into the flow path portion 23 and suppressing reaction inhibition of the solution in the flow path.
[0085] (Example)
[0086] The above-described microchannel chip and its manufacturing method will be described using specific examples, although the present disclosure is not limited to the following examples. <First Example> An example of the micro-channel chip according to the first embodiment and the method for manufacturing the same will now be described. First, a photosensitive resin for the partition wall layer was applied onto a glass substrate to form a first photosensitive resin layer. A transparent negative liquid resin (negative liquid resist) made of epoxy resin was used as the photosensitive resin for the partition wall layer. The photosensitive resin (negative liquid resist) had a glass transition temperature (TG) of 160°C. The negative liquid resist was applied onto the glass substrate using a spin coater at a rotation speed of 1100 rpm for 30 seconds. The rotation speed and time of the spin coater were adjusted so that the film thickness of the first photosensitive resin layer would be 50 μm. Next, a heat treatment (pre-baking) was performed on a hot plate at 90°C for 20 minutes to remove residual solvent contained in the photosensitive resin (negative liquid resist) for the partition layer.
[0087] Next, a photosensitive resin for the top cover was applied onto the first photosensitive resin layer to form a second photosensitive resin layer. The photosensitive resin for the top cover was the same as the negative liquid resist described above, except that its glass transition temperature (TG) was 50°C lower (110°C) than that of the photosensitive resin for the partition wall layer. Pre-baking was performed under the same conditions as for the photosensitive resin for the partition wall layer to remove residual solvent contained in the photosensitive resin for the top cover.
[0088] Next, the photosensitive resin layer (first photosensitive resin layer, second photosensitive resin layer) on the glass substrate was exposed to light to write a flow path pattern. Specifically, the photosensitive resin was exposed to light through a photomask having a pattern arrangement of microflow paths. The photomask used had a light-shielding film with a two-layer structure of chromium and chromium oxide. A proximity exposure device was used for exposure. The exposure device used a high-pressure mercury lamp as a light source, and an i-line cut filter was inserted. The exposure dose was 170 mJ / cm. 2 It was decided.
[0089] Next, the exposed photosensitive resin layer was developed to form a flow channel pattern. Specifically, the photosensitive resin layer was developed for 60 seconds using an alkaline developer (TMAH 2.38%) to dissolve the unexposed parts and pattern the flow channel structure. Next, shower cleaning with ultrapure water was performed to remove the developer from the photosensitive resin layer on the substrate, and the substrate was then dried with a spin dryer. At this stage, the upper part of the flow path pattern on the side opposite the glass substrate was open. In addition, the second photosensitive resin layer remained on the partition layer.
[0090] Next, the channel pattern was post-baked at 110°C for 30 minutes. During this process, the photosensitive resin reflowed, causing the upper portion of the channel pattern, i.e., the second photosensitive resin layer, to flow toward the center of the channel section, bonding the second photosensitive resin layers on the opposing partition layers. This formed an upper cover layer, resulting in the microchannel chip of this example. At both ends of the channel section, through-holes, i.e., input and output sections, were formed without being blocked by the upper cover layer.
[0091] In the microchannel chip according to this example, the partition layer and the upper cover layer are welded together without using an adhesive, and the upper cover layer is formed by the flow of the resin for the upper cover layer (second photosensitive resin layer) during post-baking. This prevents the adhesive components from eluting into the channel and suppresses reaction inhibition of the solution in the channel. Furthermore, 10 μL of the colored reaction solution was pipetted into the microchannel chip of this example and introduced into the inlet port of the channel. The flow was observed under a microscope. The introduced reaction solution flowed smoothly through the channel, with no leakage from the channel, and the flow was satisfactory. Therefore, it was confirmed that the microchannel chip of this example had smooth fluid flow, no leakage, and the basic performance of a microchannel chip was provided.
[0092] <Second Example> An example of the micro-channel chip according to the second embodiment and the method for manufacturing the same will now be described. A micro-channel chip according to the second embodiment was fabricated in the same manner as in the first embodiment, except that the partition layer and the upper cover layer were integrally formed. Specifically, first, in the same manner as in the first embodiment, a photosensitive resin for the partition wall layer was applied onto a glass substrate to form a first photosensitive resin layer, and a pre-baking treatment was carried out. Next, under the same exposure conditions as in the first example, the first photosensitive resin layer on the glass substrate was exposed to light to write a flow path pattern.
[0093] Next, the exposed first photosensitive resin layer was developed under the same conditions as in Example 1, the developer was removed, and the layer was dried with a spin dryer to form a flow path pattern. An example of a cross-sectional SEM image of the flow path pattern at this stage is shown in Figure 10(a). In Fig. 10(a), the recessed portion sandwiched between the opposing partition wall layers corresponds to the flow path portion of the flow path pattern. As shown in Fig. 10(a), in the flow path portion of the flow path pattern after removal of the developer and drying, the upper portion on the side opposite to the glass substrate is open. The upper opening of the flow path portion is the same as in the first embodiment.
[0094] Next, the channel pattern was post-baked in an oven at 160°C for 30 minutes. During this process, the photosensitive resin reflowed, causing the upper portions of the channel pattern, i.e., the upper sides of the partition walls, to flow toward the center of the channel, bonding the photosensitive resins (negative liquid resists) on the upper sides of the opposing partition walls. This resulted in the production of a microchannel chip according to this example.
[0095] An example of a cross-sectional SEM image of the microchannel chip after post-baking is shown in Figure 10(b). As shown in Figure 10(b), it was confirmed that after post-baking, the photosensitive resin above the channel pattern (i.e., above the partition layer) flowed and bonded near the center of the channel section, forming an upper cover layer. Furthermore, as shown in Figure 10(b), it was confirmed that the thickness of the upper cover layer formed by the flow of the partition layer becomes thinner toward the center of the flow path portion, forming a recess. Also, as shown in Figure 10(b), it was confirmed that the cross-sectional shape of the flow path portion has rounded corners. These points are the same as in the first example described above, in which the partition layer and the upper cover layer are separate bodies. At both ends of the flow path portion, an input portion and an output portion, which were through-holes, were formed without being blocked by the upper cover layer.
[0096] In the microchannel chip according to this example, fabricated as described above, the upper cover layer is formed by flowing the upper part of the partition layer during post-baking, and no adhesive is used to bond the partition layer and the upper cover layer together, which prevents adhesive components from eluting into the channel and inhibits reaction of the solution in the channel. Furthermore, a liquid transfer test was conducted on the microchannel chip of this example in the same manner as in the first example. As a result, the introduced reaction solution flowed smoothly through the channel, with absolutely no leakage from the channel, and liquid transfer was satisfactory. Therefore, it was confirmed that the microchannel chip of this example had smooth fluid flow, no leakage, and the basic performance of a microchannel chip was provided. [Industrial Applicability]
[0097] The present disclosure can be suitably used as a microchannel chip capable of forming a top cover without the need for complicated manufacturing steps, and a manufacturing method thereof, for microchannel chips intended for research purposes, diagnostic purposes, testing, analysis, culturing, and the like. [Explanation of symbols]
[0098] 1,200,400,500,600...microfluidic chip 2, 32...input section 3, 23, 43a, 53a, 63a...flow path section 4, 34...Output section 10, 20, 40, 50, 60... board 11, 21, 41a, 51a, 61a...Partition layer 12, 22, 42a, 52a, 62a...upper lid layer 25...Hot plate 120...Flow path pattern
Claims
1. A base and a partition wall portion that forms a flow path on the base; an upper cover portion formed on a surface of the partition wall opposite to the base portion and serving as a cover for the flow channel; Equipped with the partition wall and the upper cover are made of a resin material, the partition wall and the upper lid are directly bonded to each other without any adhesive layer therebetween, The upper cover has a recess in a region that overlaps with the flow channel on the side opposite to the flow channel. A microchannel chip characterized by:
2. The resin material forming the upper lid portion is a resin having thermal fluidity and a melt flow rate in the range of 1 g / 10 min or more and 100 g / 10 min or less (230 °C), The thickness of the region in which the recess is formed in the upper cover portion is reduced from the partition wall side toward the center of the flow channel. The microchannel chip according to claim 1 .
3. The upper lid portion and the partition portion are formed of a photosensitive resin, The photosensitive resins forming the upper cover and the partition are welded together.
3. The microchannel chip according to claim 1 or 2.
4. The cross-sectional shape of the flow path is rounded. The microchannel chip according to claim 2 .
5. The resin material is a photosensitive resin that is photosensitive to light with a wavelength of 190 nm or more and 400 nm or less, which is in the ultraviolet light region. The microchannel chip according to claim 1 .
6. The resin material forming the upper lid portion has a lower glass transition temperature than the resin material forming the partition portion. The microchannel chip according to any one of claims 1 to 5.
7. The resin material forming the upper lid portion has a glass transition temperature that is lower in the range of 30°C to 50°C than the resin material forming the partition portion. The microchannel chip according to claim 6 .
8. The resin material is a photosensitive resin, The photosensitive resin forming the upper lid portion has higher or lower exposure sensitivity than the photosensitive resin forming the partition portion. The microchannel chip according to any one of claims 1 to 7.
9. The difference in exposure sensitivity between the photosensitive resin forming the upper cover portion and the photosensitive resin forming the partition portion is in the range of 5 μC / cm 2 or more and 20 μC / cm 2 or less. The microchannel chip according to claim 8 .
Citation Information
Patent Citations
Liquid circuit
JP1997257748A
DNA amplifying apparatus
JP1997262084A
Microfluid device having valve
JP2006136990A
Plastic microchip, joining method therefor, and biochip or micro analytical chip using the same
JP2007240461A
Microchannel device
JP2013044528A