Microfluidic chip and method for manufacturing a microfluidic chip

Abstract

To provide a micro flow channel chip capable of removing air bubbles generated inside a micro flow channel, while preventing elution of an adhesive component into the flow channel to suppress a reaction inhibition of a solution inside the flow channel, and also to provide a manufacturing method thereof.SOLUTION: A micro flow channel chip 1 includes: a substrate 10; a partition layer 11 forming a flow channel on the substrate 10; and a top cover layer 12 formed on a surface at a side opposite to the substrate 10 of the partition layer 11 and configured to be served as a lid of a flow channel part 3. The top cover layer 12 includes an air bubble removal part 7 being part of the top cover layer 12 and configured to remove air bubbles generated in the flow channel part 3. No adhesive layer is formed between the partition layer 11 and the top cover layer 12.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] This disclosure relates to a microfluidic chip and a method for manufacturing the same. [Background technology]

[0002] In recent years, technologies have been proposed that utilize lithography and thick-film processing techniques to create minute reaction fields, enabling analysis in units of a few microliters to a few nanoliters. Technologies that utilize such minute reaction fields are called μ-TAS (Micro Total Analysis system).

[0003] μ-TAS has applications in areas such as genetic testing, chromosome testing, cell testing, and drug development, as well as in biotechnology, environmental trace substance testing, surveys of crop rearing environments, and genetic testing of crops. The introduction of μ-TAS technology offers significant benefits, including automation, increased speed, higher accuracy, lower costs, faster processing, and reduced environmental impact.

[0004] In μ-TAS, micrometer-sized channels (microchannels, microfluidics) formed on a substrate are often used, and such substrates are called chips, microchips, or microfluidic chips.

[0005] Incidentally, in microfluidic chips, bubbles may form in the reaction solution flowing through the microchannels. Bubbles can be generated, for example, by being trapped when the reaction solution or other fluid is injected into the microfluidic chip, by boiling due to heating of the reaction solution, by bubbles getting trapped due to uneven flow within the microchannels, or by foaming from the reaction solution itself. The generation of such bubbles can cause instability in the liquid flow within the microchannel and inhibit the reaction of the reaction solution.

[0006] For example, Patent Document 1 discloses a method for removing bubbles from a microchannel by attaching a bubble separation unit having a mesh-like member that allows only air to pass through and not fluid to pass through the channel, thereby removing bubbles generated by the entrainment of air into the microfluidic. Furthermore, Patent Document 2 discloses a method for manufacturing a microfluidic chip by joining components together with an adhesive. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] Japanese Patent Publication No. 2006-223118 [Patent Document 2] Japanese Patent Publication No. 2007-240461 [Overview of the project] [Problems that the invention aims to solve]

[0008] Conventionally, in the fabrication of microfluidic chips, it is common to join components together using adhesive, as described in Patent Document 2. However, when a bubble separation section, such as the one disclosed in Patent Document 1, is attached to a microfluidic channel with an adhesive, there is a problem that components of the adhesive may dissolve into the solution flowing through the microfluidic channel, which can inhibit the reaction of the solution.

[0009] Therefore, in view of the above problems, this disclosure aims to provide a microfluidic chip that can remove bubbles generated in the microfluidic channel and prevent the elution of adhesive components into the channel, thereby suppressing inhibition of the reaction of the solution in the channel, and a method for manufacturing the same. [Means for solving the problem]

[0010] To solve the above problems, a microfluidic chip according to one aspect of the present disclosure comprises a base, a partition wall portion that forms a flow channel on the base, and an upper cover portion formed on the side of the partition wall portion opposite to the base and serving as a cover for the flow channel, wherein the upper cover portion is provided with a bubble removal portion for removing bubbles generated in the flow channel, and no adhesive layer is provided between the partition wall portion and the upper cover portion. Furthermore, in order to solve the above problems, a microfluidic chip according to another aspect of the present disclosure comprises a base, a partition wall portion that forms a flow channel on the base, and an upper cover portion formed on the side of the partition wall portion opposite to the base and serving as a cover for the flow channel, wherein the upper cover portion is provided with a bubble removal portion for removing bubbles generated in the flow channel, and the upper cover portion and the partition wall portion are welded to each other. Furthermore, in order to solve the above problems, a microfluidic chip according to yet another aspect of the present disclosure is a microfluidic chip comprising a channel and an upper cover portion which serves as a cover for the channel, wherein the material of the upper cover portion is a thermally fluid resin, and the upper cover portion is provided with a bubble removal portion for removing bubbles generated in the channel.

[0011] Furthermore, a method for manufacturing a microfluidic chip according to one aspect of the present disclosure is characterized by comprising the steps of: coating a photosensitive resin onto a base; exposing the coated photosensitive resin to light; developing and washing the exposed photosensitive resin to form a partition wall portion that defines a flow channel on the base; and heating the partition wall portion to cause the photosensitive resin to flow, thereby forming an upper cover portion of the flow channel and providing through holes in the upper cover portion as bubble removal portions for removing bubbles generated in the flow channel. Further, a method for manufacturing a microchannel chip according to another aspect of the present disclosure includes a step of coating a first photosensitive resin on a base, a step of coating a second photosensitive resin on the coated first photosensitive resin, a step of exposing the first photosensitive resin and the second photosensitive resin, a step of developing and cleaning the exposed first photosensitive resin and the second photosensitive resin to form a partition wall portion defining a flow path on the base, and a step of heat-treating the second photosensitive resin on the partition wall portion to make the second photosensitive resin flow, thereby forming an upper lid portion of the flow path and providing through holes as bubble removal portions for removing bubbles generated in the flow path in the upper lid portion.

Advantages of the Invention

[0012] According to an aspect of the present disclosure, it is possible to provide a microchannel chip capable of removing bubbles generated in a microchannel, preventing elution of an adhesive component into the flow path, and suppressing inhibition of the reaction of the solution in the flow path.

Brief Description of the Drawings

[0013] [Figure 1] It is a schematic diagram showing a configuration example of a microchannel chip according to a first embodiment of the present disclosure. (a) is a plan schematic diagram showing a configuration example of a microchannel chip according to a first embodiment of the present disclosure, (b) is a plan schematic diagram showing an enlarged view of a bubble removal portion of the microchannel chip according to a first embodiment of the present disclosure, and (c) of the microchannel chip according to a first embodiment of the present disclosure is a cross-sectional schematic diagram showing a configuration example of a microchannel chip according to a first embodiment of the present disclosure. [Figure 2] It is a cross-sectional schematic diagram showing an example of a cross-sectional shape of a flow path of a microchannel chip according to a first embodiment of the present disclosure. [Figure 3] It is a cross-sectional schematic diagram showing an enlarged cross-section of a microchannel chip according to a first embodiment of the present disclosure. [Figure 4] It is a flowchart showing an example of a method for manufacturing a microchannel chip according to a first embodiment of the present disclosure. [Figure 5]A diagram for explaining part of the manufacturing process of a microchannel chip by a certain manufacturing method according to the first embodiment of the present disclosure. (a) is a schematic cross-sectional view showing a resin material coated on a substrate, (b) is a schematic cross-sectional view showing a groove formed between partition layers, and (c) is a schematic cross-sectional view showing an example of a microchannel chip manufactured by a certain manufacturing method. [Figure 6] A diagram for explaining the manufacturing process of a microchannel chip by another manufacturing method according to the first embodiment of the present disclosure. (a) is a schematic cross-sectional view showing a resin material coated on a substrate, (b) is a schematic cross-sectional view showing a groove formed between partition parts, and (c) is a schematic cross-sectional view showing an example of a microchannel chip manufactured by a certain manufacturing method. [Figure 7] A diagram for explaining the manufacturing process of a microchannel chip by yet another manufacturing method according to the first embodiment of the present disclosure. (a) is a schematic cross-sectional view showing a resin material coated on a substrate, (b) is a schematic cross-sectional view showing a groove formed between partition parts, and (c) is a schematic cross-sectional view showing an example of a microchannel chip manufactured by a certain manufacturing method. [Figure 8] (a) is a schematic plan view of a flow path pattern before the execution of heat treatment (post-bake) in the first embodiment of the present disclosure, (b) is a schematic cross-sectional view showing a cross-section obtained by cutting a substrate, a partition layer, and a second photosensitive resin layer on the partition layer that define the flow path pattern along the D-D line of (a), and (c) is a schematic cross-sectional view showing a cross-section obtained by cutting a substrate, a partition layer, and a second photosensitive resin layer on the partition layer that define the flow path pattern along the E-E line of (a). [Figure 9] (a) is a schematic plan view of a microchannel chip after the execution of heat treatment (post-bake) in the first embodiment of the present disclosure, (b) is a schematic cross-sectional view showing a cross-section obtained by cutting the microchannel chip along the D-D line of (a), and (c) is a schematic cross-sectional view showing a cross-section obtained by cutting the microchannel chip 700 along the E-E line of (a). [Figure 10] A schematic cross-sectional view showing an example of the cross-sectional shape of a flow path of a microchannel chip according to the second embodiment of the present disclosure. [Figure 11]The figure illustrates the manufacturing process of a microfluidic chip by a manufacturing method of a microfluidic chip according to a second embodiment of the present disclosure, where (a) is a schematic plan view showing an example of a flow channel pattern, (b) is a schematic cross-sectional view of the input region of the flow channel pattern, (c) is a schematic cross-sectional view of the flow channel region of the flow channel pattern, (d) is a schematic plan view of a microfluidic chip manufactured by the manufacturing method, (e) is a schematic cross-sectional view of the input portion of a microfluidic chip manufactured by the manufacturing method, and (f) is a schematic cross-sectional view of the flow channel portion of a microfluidic chip manufactured by the manufacturing method. [Figure 12] (a) is a schematic plan view of the flow channel pattern before heat treatment (post-bake) in the second embodiment of the present disclosure, and (b) is a schematic plan view of the microfluidic chip after heat treatment (post-bake) in the second embodiment of the present disclosure. [Figure 13] This is a schematic cross-sectional view showing an example of the cross-sectional shape of the channel of a microfluidic chip according to the third embodiment of this disclosure. [Figure 14] This flowchart shows an example of a method for manufacturing a microfluidic chip according to the third embodiment of this disclosure. [Figure 15] (a) is a cross-sectional SEM view of the microfluidic chip in the example before post-baking, and (b) is a cross-sectional SEM view of the microfluidic chip in the example after post-baking. [Modes for carrying out the invention]

[0014] The present disclosure will be described below through embodiments, but these embodiments are not intended to limit the invention as defined in the claims. Furthermore, not all combinations of features described in the embodiments are necessarily essential to the solution of the invention. In addition, the drawings are schematic representations of the invention as defined in the claims, and the dimensions such as width and thickness of each part differ from those of reality, as do their proportions.

[0015] A microfluidic chip according to the first embodiment of this disclosure will be described below. In the following description, the substrate side of the microfluidic chip may be referred to as "bottom," and the side opposite the substrate side (the lid side) may be referred to as "top."

[0016] As a result of diligent research, the inventors have discovered that by heating and flowing a resin material in a microfluidic chip, it is possible to form an upper lid that serves as a cover for the channel section, thereby enabling the creation of an upper lid on the partition section without the use of adhesive. Similarly, they have also discovered that the flow of the resin material makes it possible to create a structure in the upper lid that can remove air bubbles. As a result, the inventors have invented a microfluidic chip and a method for manufacturing the same that can efficiently remove air bubbles contained in the microfluidic channels and prevent the dissolution of adhesive components into the channels, thereby suppressing inhibition of the reaction of the solution in the channels. The following describes the various aspects of each embodiment of this disclosure with reference to the drawings.

[0017] 1. First Embodiment (1.1) Basic configuration of a microfluidic chip Figure 1 is a schematic diagram illustrating an example configuration of a microfluidic chip 1 according to the first embodiment of this disclosure (hereinafter referred to as "this embodiment"). Specifically, Figure 1(a) is a schematic plan view of the microfluidic chip 1 of this embodiment. Figure 1(b) is a schematic plan view showing an enlarged view of the bubble removal section 7 provided on the upper lid layer 12 of the microfluidic chip 1 shown in Figure 1(a). Figure 1(c) is a schematic cross-sectional view showing a cross-section obtained by cutting the region of the microfluidic chip 1 including the bubble removal section 7 along line AA shown in Figure 1(b).

[0018] As shown in Figure 1(a), the microfluidic chip 1 comprises an input section 2 for introducing a fluid (e.g., liquid), a flow channel section 3 through which the fluid introduced from the input section 2 flows, and an output section 4 for discharging the fluid from the flow channel section 3. In the microfluidic chip 1, the upper surface of the flow channel section 3 is covered by an upper cover layer 12, and the input section 2, the output section 4, and the bubble removal section 7 are through holes provided in the upper cover layer 12. Details of the upper cover layer 12 and the bubble removal section 7 will be described later. Figure 1(a) illustrates the flow channel 3 as it is visible through the transparent top cover layer 12.

[0019] In the microfluidic chip 1, at least one input section 2 and one output section 4 are required, and multiple input sections 2 and 4 of each are also possible. Furthermore, multiple flow channels 3 may be provided in the microfluidic chip 1, and the design may allow for the merging and separation of fluids introduced from the input section 2. Additionally, the bubble removal section 7 may be located at any position in the upper cover layer 12 that faces the flow channel section 3. It is appropriately positioned in the most effective location for the configuration and application of the microfluidic chip 1.

[0020] Here, we will describe the details of the components that make up the channel section 3 in the microfluidic chip 1. As shown in Figures 1(a) to 1(c), the microfluidic chip 1 comprises a substrate (an example of a base) 10, a partition layer (an example of a partition) 11 that forms a channel on the substrate 10, and an upper cover layer (an example of an upper cover) 12 formed on the side of the partition layer 11 opposite to the substrate 10 and serving as a cover for the channel section 3. In this embodiment, the upper cover layer 12 is provided with a bubble removal section 7 that removes bubbles generated in the channel section 3. As will be described in more detail later, in this embodiment the bubble removal section 7 has a through hole 17 that penetrates the upper cover in the thickness direction. In the microfluidic chip 1, the fluid channel 3 through which the fluid introduced from the input section 2 flows is a region surrounded by the substrate 10, the partition layer 11, and the top cover layer 12. The fluid channel 3 is defined by opposing partition layers 11 provided on the substrate 10, and the side opposite to the substrate 10 is covered by the top cover layer 12, which serves as a cover material. In other words, the fluid channel 3 is a space composed of the substrate 10, the partition layer 11, and the top cover layer 12. As described above, fluid is introduced into the fluid channel 3 from the input section 2 (see Figure 1(a)) provided on the top cover layer 12, and the fluid that has flowed through the fluid channel 3 is discharged from the output section 4.

[0021] As will be described in more detail later, in the microfluidic chip 1 according to this embodiment, no adhesive layer is provided between the partition layer 11 and the top cover layer 12. In this embodiment, the partition layer 11 and the top cover layer 12 are welded to each other. Here, the adhesive layer is a layer containing an adhesive and is used to bond multiple members together. By welding (joining) the partition layer 11 and the top cover layer 12 without providing an adhesive layer, the microfluidic chip 1 can prevent the elution of adhesive components into the channel and suppress inhibition of the reaction of the solution in the channel.

[0022] Furthermore, as shown in Figure 1(c), the partition layer 11 and the top lid layer 12 are separate components. Here, "separate components" means, for example, that the partition layer 11 and the top lid layer 12 are formed from different resin materials. In this case, the resin material forming the top lid layer 12 can be selected to have properties suitable for forming the top lid and through holes for bubble removal, such as having a different glass transition temperature or exposure sensitivity compared to the partition layer 11. The disclosure is not limited to this, and the partition layer 11 and the top lid layer 12 may be considered separate components if they have a laminated structure and an interface is formed between them. In this case, the partition layer 11 and the top lid layer 12 may be formed from the same resin material.

[0023] (1.1.1) Circuit board The substrate 10 is the basic component of the microfluidic chip 1, and the channel section 3 is formed by the partition layer 11 provided on the substrate 10. In other words, the substrate 10 and the partition layer 11 can be considered the main body of the microfluidic chip 1. The substrate 10 can be formed from either a light-transmitting material or an opaque material. For example, if the state inside the channel section 3 (fluid state) is to be detected and observed by light, a material with excellent transparency to light can be used. As a light-transmitting material, resin or glass can be used. From the viewpoint of suitability for forming the main body of the microfluidic chip 1, examples of resins that can be used as the light-transmitting material for forming the substrate 10 include acrylic resin, methacrylic resin, polypropylene, polycarbonate resin, cycloolefin resin, polystyrene resin, polyester resin, urethane resin, silicone resin, and fluororesin.

[0024] Furthermore, if it is not necessary to detect and observe the state of the fluid inside the channel section 3 using light, a non-transparent material may be used. Examples of non-transparent materials include silicon wafers and copper plates. The thickness of the substrate 10 is not particularly limited, but since a certain degree of rigidity is required in the channel formation process, a range of 10 μm (0.01 mm) to 10 mm is preferred.

[0025] (1.1.2) Partition layer The partition layer 11 is provided on the substrate and forms the flow channel 3. The partition layer 11 can be made of a resin material. For example, a photosensitive resin can be used as the resin material for the partition layer 11.

[0026] The photosensitive resin forming the partition layer 11 is preferably a photosensitive resin that is photosensitive to light with wavelengths of 190 nm to 400 nm, which are in the ultraviolet light region. As the photosensitive resin, a photoresist such as a liquid resist or a dry film resist can be used. These photosensitive resins may be either positive type, where the photosensitive region dissolves, or negative type, where the photosensitive region becomes insoluble. A photosensitive resin composition suitable for forming the partition layer 11 in the microfluidic chip 1 is a radical negative type photosensitive resin containing an alkali-soluble polymer, an addition-polymerizable monomer, and a photopolymerization initiator. For example, as the photosensitive resin material, 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 can be used individually, in combination, or copolymerized. In this embodiment, the resin material of the partition layer 11 is not limited to a photosensitive resin, but may also be silicone rubber (PDMS: polydimethylsiloxane) or synthetic resin. Examples of synthetic resins that can be used include polymethyl methacrylate resin (PMMA), polycarbonate (PC), polystyrene resin (PS), polypropylene (PP), cycloolefin polymer (COP), and cycloolefin copolymer (COC). It is desirable that the resin material of the partition layer 11 be appropriately selected according to the application. Furthermore, the thickness of the partition layer 11 on the substrate 10, i.e., the height of the flow channel 3, is not particularly limited, but the height of the flow channel 3 must be greater than the amount of substance to be analyzed and inspected (e.g., drugs, bacteria, cells, red blood cells, white blood cells, etc.) contained in the fluid introduced into the flow channel 3. For this reason, the thickness of the partition layer 11, i.e., the height (depth) of the flow channel 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 channel 3 needs to be larger than that of the substance to be analyzed and inspected, the width of the flow channel 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 channel length determined by the partition layer 11 is preferably in the range of 10 mm to 100 mm, more preferably in the range of 30 mm to 70 mm, and even more preferably in the range of 40 mm to 60 mm, in order to ensure sufficient reaction time for the reaction solution.

[0027] (1.1.3) Upper lid layer In the microfluidic chip 1 according to this embodiment, the upper cover layer 12 is a cover material that covers the fluid channel 3, as shown in Figures 1(a) to 1(c). As described above, the upper cover layer 12 is provided on the side of the partition wall layer 11 opposite to the substrate 10, and faces the substrate 10 across the partition wall layer 11. More specifically, as shown in Figure 1(c), in a cross-sectional view, the side ends of the upper cover layer 12 are supported by the partition wall layer 11, the central region faces the substrate 10, and this central region defines the upper part of the fluid channel 3.

[0028] The top lid layer 12 can be formed from either a light-transmitting material or an opaque material. For example, if the condition inside the flow channel is to be detected and observed by light, a material with excellent transparency to such light can be used. As a light-transmitting material, resin can be used. As the resin forming the top lid layer 12, a photosensitive resin similar to that used for the partition layer 11 can be used. Furthermore, the photosensitive resin used for the upper lid layer 12 is a thermally fluid resin. By using a thermally fluid photosensitive resin as the material for the upper lid layer 12, it becomes possible to form the upper lid layer 12 in the microfluidic chip 1 without using an adhesive. This prevents the elution of adhesive components into the channel and suppresses inhibition of the reaction of the solution in the channel.

[0029] Furthermore, conventional methods of joining the partition layer and the lid member using adhesives have required advanced equipment and technology, resulting in complex manufacturing processes. In the microfluidic chip 1 according to this embodiment, by using a heat-fluidable resin (in this example, a photosensitive resin) as the material for the upper lid layer 12, the upper lid layer 12 can be formed on the partition layer 11 more easily than in conventional methods. This reduces the complexity of the manufacturing process.

[0030] The photosensitive resin having thermal fluidity preferably has a melt flow rate (MFR) within the range of 1 g / 10 min to 100 g / 10 min (230°C). This allows for easy formation of the top lid layer 12 in the manufacturing process described later.

[0031] As will be explained in more detail later, the top lid layer 12 is formed by heat treatment to flow (reflow) a photosensitive resin with thermal fluidity, which is formed on the partition wall layer 11, onto the flow channel section 3. Therefore, as shown in Figure 2, the top lid layer 12 has a recess 120. In other words, the top lid layer 12 has a concave region. Specifically, the thickness of the top lid layer 12 decreases from the partition wall layer 11 side toward the central part of the flow channel section 3, which forms the recess 120 in cross-sectional view.

[0032] Furthermore, the top lid layer 12 may be formed of a resin material with a lower glass transition temperature (Tg) than the partition layer 11. For example, the top lid layer 12 may have a glass transition temperature that is 30°C to 50°C lower than that of the partition layer 11. In this case, since the photosensitive resin forming the partition layer 11 has a higher glass transition temperature (Tg) than the photosensitive resin forming the top lid layer 12, almost no resin flow occurs. Therefore, it is possible to suppress the flow in the partition layer 11 and the resulting change in the flow path pattern during the formation of the top lid layer 12. Furthermore, the glass transition temperature (Tg) of the upper lid layer 12 is preferably in the range of 100°C to 300°C.

[0033] Furthermore, the upper lid layer 12 has an exposure sensitivity of 5 μC / cm². 2 More than 50μC / cm2 The following range is preferable. Furthermore, the exposure sensitivity of the top lid layer 12 may differ from that of the partition layer 11. For example, the exposure sensitivity of the top lid layer 12 may be 5 μC / cm² compared to that of the partition layer 11. 2 More than 20μC / cm 2 Higher exposure sensitivity is acceptable within the following range. For example, the upper lid layer 12 has a temperature of 5 μC / cm² relative to the partition layer 11. 2 More than 20μC / cm 2 The exposure sensitivity may be low within the following range. Thus, the upper cover layer 12 may have a configuration that is more or less sensitive to exposure than the partition layer 11.

[0034] If the upper lid layer 12 has a different exposure sensitivity than the partition layer 11, setting the exposure amount to match the photosensitive resin forming the partition layer 11 ensures that the opening width of the photosensitive resin forming the partition layer 11, i.e., the width of the flow channel pattern, is sufficiently large. Therefore, even if flow occurs in the resin for the partition layer when the resin material for the upper lid layer is flowed during the formation of the upper lid layer 12, the opening width of the photosensitive resin forming the partition layer 11 can be made sufficiently large, thus maintaining sufficient space for the flow channel section 3.

[0035] (1.1.3.1) Bubble removal section Returning to Figure 1, as shown in Figures 1(a) to 1(c), the upper cover layer 12 is provided with a bubble removal section 7 for removing bubbles that form in the flow channel section 3. Specifically, the bubble removal section 7 is formed as part of the upper cover layer 12. As a result, the microfluidic chip 1 can remove air bubbles that form in the channel section 3 and prevent the elution of adhesive components into the channel, thereby suppressing inhibition of the reaction of the solution in the channel. Here, bubbles generated in the flow channel 3 refer to, for example, bubbles being drawn in when a fluid such as a reaction solution is injected (introduced) from the input section 2 into the flow channel 3, boiling due to heating of the introduced reaction solution, bubbles getting trapped due to uneven flow of the reaction solution in the flow channel 3, or foaming from the reaction solution itself.

[0036] As shown in Figure 1(a), the bubble removal section 7 is provided in the region of the upper lid layer 12 facing the flow path section, along the direction of travel of the flow path section 3. Note that in Figure 1(a), for ease of understanding, the region in the upper lid layer 12 where the bubble removal section 7 is provided is shown with a rectangular frame, but this rectangular frame is not an actual component. In the upper lid layer 12, there may be one (one location) bubble removal section 7, or multiple (multiple locations) may be provided as needed. Furthermore, as shown in Figures 1(b) and 1(c), the bubble removal section 7 has through-holes 17 that penetrate the upper lid layer 12 in the thickness direction. As shown in Figure 1(b), the through-holes 17 communicate with the outside (external environment) of the flow channel section 3. This ensures that bubbles are reliably removed from the flow channel section 3. Specifically, when a fluid such as a reaction solution passes through the region where the through-holes 17 are provided at the top within the flow channel section 3, the gas that forms bubbles is released through the through-holes 17 into the external environment (atmosphere) of the flow channel section 3. Therefore, bubbles can be efficiently removed from the flow channel section 3.

[0037] Furthermore, the bubble removal section 7 is made of the same resin as the top lid layer 12, that is, a photosensitive resin with thermal fluidity. As will be described in more detail later, by using a photosensitive resin with thermal fluidity as the material for the top lid layer 12, the bubble removal section 7, which has micro-holes (through holes 17), can be formed simultaneously with the top lid layer 12 as part of the top lid layer 12, without joining separate components with adhesives or the like. Also, as described above, in the microfluidic chip 1, the top lid layer 12 having the bubble removal section 7 is welded to the partition layer 11 without using an adhesive layer. As a result, the microfluidic chip 1 can remove bubbles generated in the flow channel section 3 and prevent the dissolution of adhesive components into the flow channel, thereby suppressing inhibition of the reaction of the solution in the flow channel.

[0038] In this example, the bubble removal section 7 is composed of a plurality of through holes 17. The plurality of through holes 17 are formed along the direction of travel of the flow channel section 3. In the microfluidic chip 1 according to this embodiment, the bubble removal section 7 may have one or a plurality of through holes 17.

[0039] When the bubble removal section 7 has multiple through holes 17, the distance from one through hole 17 to the next, i.e., the spacing S of the multiple through holes 17 shown in Figure 1(b), is preferably within the range of 5 μm to 1000 μm. By setting the spacing S within the aforementioned range, bubbles generated in the flow path section 3 can be removed more efficiently.

[0040] Furthermore, as shown in Figure 1(c), in this embodiment, the through-hole 17 of the bubble removal section 7 has a diameter equal to the diameter of the opening end 17a on the flow path section 3 side and the diameter equal to the diameter of the opening end 17b on the opposite side of the flow path section 3, and the width of the through-hole 17 penetrating the upper cover layer 12 in the thickness direction is constant. However, this disclosure is not limited thereto, and for example, the through-hole 17 may have a configuration in which the diameter of the opening end 17a on the flow path section 3 side and the diameter of the opening end 17b on the opposite side of the flow path section 3 are different, and the width in the thickness direction changes accordingly. For example, the through-hole 17 may have a shape in which the diameter of the opening end 17a is larger than the diameter of the opening end 17b, and the width in the thickness direction narrows from the opening end 17a to the opening end 17b (for example, a trapezoidal shape in the cross-sectional view shown in Figure 1(c)). Furthermore, the through hole 17 may have a shape in which the diameter of the open end 17a is smaller than that of the open end 17b, and the width in the thickness direction increases from the open end 17a to the open end 17b (for example, an inverted trapezoidal shape in the cross-sectional view shown in Figure 1(c)). Furthermore, the through hole 17 may have the same diameter at the open end 17a and the open end 17b, and its width may change in the intermediate portion in the thickness direction (between the open end 17a and the open end 17b). In this case, for example, the through hole 17 may have a shape in which the width of the intermediate portion becomes narrower (the intermediate portion is constricted) or a shape in which the width of the intermediate portion becomes wider, as shown in the cross-sectional view in Figure 1(c).

[0041] Furthermore, as shown in Figure 1(b), the through-holes 17 constituting the bubble removal section 7 may have circular openings 17a and 17b in a plan view. Circular shapes include perfect circles, ellipses, egg shapes, oblong shapes, etc. When the openings 17a and 17b of the through-holes 17 are circular, the diameter (maximum diameter) of the openings 17a and 17b is preferably within the range of 1 μm to 100 μm. This allows for bubble removal without causing liquid leakage from the flow path section 3.

[0042] Furthermore, in this disclosure, the shape of the open ends 17a and 17b of the through hole 17 in plan view is not limited to a circle. The shape of the open ends 17a and 17b of the through hole 17 may be polygonal in plan view. In this case, the polygon may be a rounded shape in which each side is connected by an arc. Also, when the shape of the open ends 17a and 17b of the through hole 17 is polygonal, it is preferable that the longitudinal width of the open ends 17a and 17b is within the range of 1 μm to 100 μm. This makes it possible to remove air bubbles without causing liquid leakage from the flow channel 3. The shape and diameter of the opening ends 17a and 17b of the through hole 17 can be appropriately designed within the above range according to the width and length of the flow channel 3. Furthermore, the shapes of the open ends 17a and 17b do not have to be the same. For example, one of the open ends 17a and 17b may be circular, while the other is polygonal.

[0043] Thus, in the microfluidic chip 1 according to this embodiment, the upper lid layer 12 has the function of a lid material and the function of a bubble removal section.

[0044] (1.1.4) Flow channel configuration Figure 3 shows an example of the cross-sectional shape of the channel section 3 of the microfluidic 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, that each side of the cross-section of the channel section 3 in the cross-sectional shape is connected by an arc). This makes it possible to stabilize the delivery speed and flow rate of the fluid (e.g., reaction solution) in the channel section 3 and suppress the accumulation of the substance to be inspected at the corners. Here, the cross-sectional shape of the flow channel section 3 in this embodiment will be explained using Figure 3. Figure 3 is a schematic enlarged cross-sectional view illustrating the cross-section of the flow channel section 3 having rounded corners. As shown in Figure 3, the area of ​​the virtual cross-section A1 when the cross-sectional shape of the flow channel section 3 is rectangular differs from the area of ​​the cross-section of the flow channel section 3 having rounded corners. Specifically, as shown in Figure 3, the cross-section of the flow channel section 3 has arc shapes at the four corners. Therefore, the area of ​​the cross-section of the flow channel section 3 is smaller than the virtual cross-section A1 by the sum of the areas of the virtual corners A11, A12, A13, and A14. In this embodiment, the cross-section of the flow channel section 3, which has a rounded corner shape, is acceptable as long as the area of ​​the cross-section of the flow channel section 3 is within the range of 95% to 98% of the surface area of ​​the virtual cross-section A1. In Figure 3, the cross-section of the flow channel section 3 is shown as a rounded rectangle, but it is not limited to this, and may be a shape other than a rectangle (a rounded polygon). In this case as well, the area of ​​the cross-section of the flow channel section 3 is acceptable as long as it is within the range of 95% to 98% of the virtual cross-section when the corners are not rounded.

[0045] Furthermore, it is preferable that the ten-point surface roughness Rz of the flow channel section 3 is within the range of 0.001 μm to 0.03 μm. Here, the ten-point surface roughness Rz of the flow channel section 3 refers to the roughness of the side surface of the partition wall layer 11 on the flow channel section 3 side and the surface of the substrate 10 on the flow channel section 3 side. By appropriately designing the ten-point surface roughness Rz within the above range, inspections can be performed according to the reaction solution, the object to be inspected, and the desired inspection conditions. For example, if the surface roughness Rz of the flow channel 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 object to be inspected and the inner surface of the flow channel 3 can be reduced, thereby improving the fluid delivery performance (e.g., fluid delivery speed and flow rate).

[0046] Furthermore, if the surface roughness Rz is greater than 0.02 μm and within the range of 0.03 μm or less, the liquid delivery rate can be reduced to ensure that the fluid introduced into the flow channel 3 and the substance to be inspected remain in the flow channel 3 for a sufficient amount of time, i.e., reaction time. Furthermore, when the surface roughness Rz is greater than 0.01 μm and within the range of 0.02 μm or less, it is possible to achieve both an appropriate liquid delivery rate and sufficient reaction time for the fluid and the substance being inspected within the flow channel section 3. Furthermore, the surface roughness of the channel section 3 can be appropriately controlled during the manufacturing of the microfluidic chip 1 by known etching methods or the like.

[0047] (1.2) Method for manufacturing microfluidic chips Next, a method for manufacturing the microfluidic chip 1 according to this embodiment will be described. Figure 4 is a flowchart showing an example of a method for manufacturing the microfluidic chip 1 according to this embodiment. Here, we will explain using the case where the partition layer 11 is formed from a photosensitive resin as an example.

[0048] (Step S1) In the manufacturing method of the microfluidic chip 1 according to this embodiment, first a partition wall layer 11 is placed on the substrate 10. A step is performed to coat a partition resin (an example of a first photosensitive resin) for forming the partition layer 11. This provides a resin layer on the substrate 10 for forming the partition layer 11. In the manufacturing method of the microfluidic 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.

[0049] A method for forming a photosensitive resin layer on the substrate 10 is, for example, by coating the substrate 10 with a photosensitive resin. The coating can be performed by, for example, spin coating, spray coating, or bar coating, and among these, spin coating is preferred from the viewpoint of film thickness controllability. Various forms of photosensitive resin, such as liquid, solid, gel, or film, can be coated onto the substrate 10. Among these, it is preferable to form the photosensitive resin layer with a liquid resist. Depending on the characteristics of the flow channel pattern, either a positive-type or negative-type resist may be used as appropriate. Furthermore, a resin (for example, a photosensitive resin) can be coated onto the substrate 10 such that the thickness of the resin layer (for example, a photosensitive resin layer), i.e., the thickness of the partition layer 11, is within the range of 1 μm to 500 μm.

[0050] (Step S2) After forming a first photosensitive resin layer on the substrate 10 using a partition resin, a heat treatment (pre-bake treatment) is performed to remove the solvent contained in the resin (e.g., photosensitive resin) coated on the substrate 10. In the manufacturing method of the microfluidic chip 1 according to this embodiment, the pre-bake treatment is not an essential step and can be performed 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-bake temperature and time should be set to optimal conditions according to the properties of the photosensitive resin. To improve the adhesion between the substrate and the photosensitive resin, HMDS treatment or a thin film of resin may be applied to the substrate as needed.

[0051] (Step S3) Next, a step is performed to coat the first photosensitive resin layer with a top lid resin (an example of a second photosensitive resin) for forming the top lid layer 12. This provides a resin layer for forming the top lid layer 12 on the pre-baked partition resin. In the manufacturing method of the microfluidic chip 1 according to this embodiment, for example, a resin layer (second photosensitive resin layer) made of a photosensitive resin with thermal fluidity is formed on the substrate 10. The method for forming the second photosensitive resin layer on the substrate 10 can be the same as the method for forming the first photosensitive resin layer in step S1 above.

[0052] (Step S4) Next, a second photosensitive resin layer is formed on the first photosensitive resin layer made of the partition resin using the top lid resin. Then, a heat treatment (pre-bake treatment) is performed to remove the solvent contained in the top lid resin coated on the first photosensitive resin layer. Pre-bake treatment in this step is not mandatory and, similar to the pre-bake treatment in step S2 above, can be performed under optimal conditions (temperature, time) according to the properties of the resin. In addition, to improve the adhesion between the first photosensitive resin layer and the second photosensitive resin layer, HMDS treatment or a thin film of resin may be applied to the substrate as needed. As a result, two photosensitive resin layers are formed on the substrate 10.

[0053] As shown in steps S1 to S4 above, the two photosensitive resin layers (first photosensitive resin layer, second photosensitive resin layer) for forming the partition wall layer 11 and the top cover layer 12 are welded together without the use of adhesive. In other words, in the microfluidic chip 1 according to this embodiment, the partition wall layer 11 and the top cover layer 12 are welded to each other. In other words, in the microfluidic chip 1 according to this embodiment, the partition wall layer 11 and the top cover layer 12 can be joined without the use of an intermediate member (for example, adhesive). This prevents the outflow of adhesive components into the flow channel 3 and also prevents bonding defects caused by uneven film thickness of the adhesive. In this embodiment, two layers of photosensitive resin are used, but the system is not limited to this, and three or more layers may be used.

[0054] (Step S5) Next, a process is performed to expose the resin (e.g., a first photosensitive resin layer, a second photosensitive resin layer) coated on the substrate 10. Specifically, a channel pattern is drawn on the photosensitive resin coated on the substrate 10 by exposure. Exposure can be performed, for example, using an exposure apparatus that uses ultraviolet light as a light source or a laser drawing apparatus. Among these, exposure using proximity exposure or a contact exposure apparatus that uses ultraviolet light as a light source is preferred. In the case of a proximity exposure apparatus, exposure is performed via a photomask having a channel pattern arrangement in the microchannel chip 1. The photomask can be one such photomask with a two-layer structure of chromium and chromium oxide as the light-shielding film.

[0055] If the photosensitive resin (first photosensitive resin layer, second photosensitive resin layer) coated on the substrate 10 is a positive-type resist, the exposed area dissolves to form the channel section 3, and the photosensitive resin remaining in the unexposed area becomes the partition layer 11 and the top cover layer 12. If the photosensitive resin coated on the substrate 10 is a negative-type resist, the photosensitive resin remaining in the exposed area becomes the partition layer 11 and the top cover layer 12, and the unexposed area dissolves to form the channel section 3. Thus, in the manufacturing method of the microfluidic chip 1 according to this embodiment, the partition layer 11 constituting the channel section 3 can be formed on the substrate 10 using photolithography.

[0056] Furthermore, when using a chemically amplified resist or the like to form the resin layer on the substrate 10, it is advisable to perform further heat treatment (post-exposure bake: PEB) after exposure to promote the catalytic reaction of the acid generated by exposure.

[0057] (Step S6) Next, the exposed photosensitive resin is developed to form a channel pattern. Development is carried out by the reaction of the photosensitive resin with the developer using a developing device such as a spray, dip, or paddle type. The developer can be, for example, an aqueous sodium carbonate solution, tetramethylammonium hydroxide, potassium hydroxide, or an organic solvent. The developer should be the most suitable one for the characteristics of the photosensitive resin, and is not limited to these. Furthermore, the concentration and development time can be adjusted to the optimal conditions according to the characteristics of the photosensitive resin.

[0058] (Step S7) Next, a step is performed to completely remove the developer used for development 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, a suitable washing water can be used from, for example, pure water or isopropyl alcohol, to remove the developer used in the development process. After washing, drying is performed by a spin dryer, IPA vapor dryer, or natural drying. Even at this stage, a second photosensitive resin layer made of resin for the top lid remains on the partition wall layer 11.

[0059] (Step S8) Next, a heat treatment (post-bake) is performed on the partition layer 11 and the second photosensitive resin layer that form the flow channel pattern, i.e., the flow channel section 3. This post-bake treatment removes residual moisture from developing and washing. This post-bake treatment also forms the upper cover layer 12, which acts as a lid for the flow channel section 3 and defines the upper part of the flow channel section 3, and the bubble removal section 7, which removes bubbles that form inside the flow channel section 3. Specifically, this post-bake treatment promotes the flow (reflow) of the upper cover resin, which is a fluid photosensitive resin, and allows the through-holes 17 that make up the upper cover layer 12 and the bubble removal section 7 of the flow channel section 3 to be formed. The temperature and time of the post-bake are carried out under optimal conditions according to the characteristics of the upper cover resin. As shown in Figure 1, the upper cover layer 12 is a lid material that covers the flow channel section 3 and is formed on the flow channel section 3. The input section 2 and output section 4 are open and not covered by the upper cover layer 12. Furthermore, the post-bake treatment is performed using, for example, a hot plate or an oven. If drying is insufficient in the washing process of step S7 above, developer solution and moisture from washing may remain in the partition layer 11. Also, solvents that were not removed in the pre-bake treatment may remain in the partition layer 11. These can be removed by performing a post-bake treatment.

[0060] As described above, the manufacturing method of the microfluidic chip 1 according to this embodiment includes the steps of: coating a partition resin onto a substrate 10 (step S1 above); coating a top cover resin on the coated 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 flow channel portion 3 on the substrate 10 (steps S6 and S7 above); and heating the top cover resin on the partition layer 11 to make the top cover resin flow, thereby forming a top cover layer 12 for the flow channel portion 3 and providing through holes 17 in the top cover layer 12 as bubble removal portions 7 for removing bubbles generated in the flow channel portion 3 (step S8 above). This allows the partition layer 11 and the upper lid layer 12 to be welded together without the use of adhesive, preventing the elution of adhesive components into the flow channel 3 and suppressing inhibition of the reaction of the solution in the flow channel.

[0061] (1.3) Details of the manufacturing process for the partition layer and the top cover layer In the manufacturing method of the microfluidic chip 1 according to this embodiment, each manufacturing process is adjusted according to the physical properties of the partition resin for forming the partition layer 11 and the top cover resin for forming the top cover layer 12. Specific examples are given below. (1.3.1) Formation of partition layer and upper lid layer using resins with different glass transition temperatures The formation of the partition layer 11 and the top cover layer 12 when the partition resin and the top cover resin have different glass transition temperatures will be explained with reference to Figure 5. Figure 5(a) is a schematic cross-sectional view showing the first photosensitive resin layer 41 and the second photosensitive resin layer 42 formed on the substrate 40, Figure 5(b) is a schematic cross-sectional view showing the flow channel pattern on the substrate 40, and Figure 5(c) is a schematic cross-sectional view showing the general configuration of the microfluidic chip 400 according to this example. This example describes a method for manufacturing a microfluidic chip under the condition that the glass transition temperature (Tg) of the top cover resin is lower than the glass transition temperature (Tg) of the partition resin (Glass transition temperature (Tg) of the top cover resin < Glass transition temperature (Tg) of the partition resin.

[0062] As shown in Figure 5(a), in this example, in the coating process of step S1, a photosensitive resin for partitions is applied to the substrate 40 to form a first photosensitive resin layer 41. The photosensitive resin for partitions is applied to the substrate 40 to a desired thickness, for example, by spin coating. In this example, in step S3, a photosensitive resin for the top lid is applied on top of the first photosensitive resin layer 41 to form a second photosensitive resin layer 42. In this example, the photosensitive resin for the top lid that forms the second photosensitive resin layer 42 has a lower glass transition temperature (Tg) than the photosensitive resin for partitions that forms the first photosensitive resin layer 41. The second photosensitive resin layer 42 is applied to the first photosensitive resin layer 41 to a desired thickness by spin coating, similar to the first photosensitive resin layer 41.

[0063] In this example, in the exposure step S5, a channel pattern is drawn 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 apparatus is used that uses light with a wavelength of 350 nm to 400 nm, which is in the ultraviolet region, as the light source. Next, in the development step S6, the exposed first photosensitive resin layer 41 and the second photosensitive resin layer 42 are developed to form a channel pattern 43. Here, for example, an aqueous sodium carbonate solution is used as the developer by spraying. Next, the developer is completely removed from the first photosensitive resin layer 41 and the second photosensitive resin layer 42 developed in step S7 by washing. Here, for example, ultrapure water is used for washing by spraying. As a result, a partition layer 41a is formed as shown in Figure 5(b), and the channel pattern 43 is defined.

[0064] Next, the microfluidic chip with the flow channel pattern 43 formed on it is subjected to the heat treatment (post-bake) of 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 second photosensitive resin layer 42. In this example, the heat treatment promotes the flow (reflow) of the second photosensitive resin layer 42, i.e., the top cover resin, and the top cover resin flows from the opposing left and right partition wall layers 11 towards the center of the flow channel pattern 43. The top cover resin that has flowed from the partition wall layer 41a is bonded on the side opposite to the substrate 40, i.e., on the upper side of the flow channel pattern 43, forming the top cover layer 42a. As a result, as shown in Figure 5(c), the upper part of the flow channel pattern 43 is covered with the top cover layer 42a, the flow channel section 43a is formed, and the microfluidic chip 400 is manufactured.

[0065] As in this example, when the glass transition temperature (Tg) of the first photosensitive resin layer 41 forming the partition wall layer 41a, i.e., the partition wall resin, is higher than the glass transition temperature (Tg) of the second photosensitive resin layer 42, i.e., the top lid resin, even when the top lid resin flows (reflow) due to heat treatment, almost no flow occurs in the partition wall resin. Therefore, by satisfying the condition "glass transition temperature (Tg) of the top lid resin < glass transition temperature (Tg) of the partition wall resin", the top lid resin can be flowed without causing deformation of the flow path pattern due to the flow of the top lid resin, and the top lid layer 42a can be easily formed.

[0066] (1.3.2) Formation of partition layer and upper lid layer using resins with different exposure sensitivities (1) The formation of the partition layer 11 and the top cover layer 12 when the partition resin and the top cover resin have different exposure sensitivities will be explained with reference to Figure 6. Figure 6(a) is a schematic cross-sectional view showing the first photosensitive resin layer 51 and the second photosensitive resin layer 52 formed on the substrate 50, Figure 6(b) is a schematic cross-sectional view showing the flow channel pattern on the substrate 50, and Figure 6(c) is a schematic cross-sectional view showing the general configuration of the microfluidic chip 500 according to this example. In this example, the exposure sensitivity (C / cm²) of the resin for the top cover is 2 ) is the exposure sensitivity (C / cm²) of the partition resin. 2 ) is lower than (exposure sensitivity (C / cm²) of the resin for the top cover2 )Exposure sensitivity (C / cm of the resin for the partition wall 2 ) will be used to explain the manufacturing method of the microchannel chip under this condition.

[0067] As shown in Fig. 6(a), in this example, in the coating process of step S1, a photosensitive resin for the partition wall is coated on the substrate 50 to form a first photosensitive resin layer 51. The photosensitive resin for the partition wall is coated on the substrate 50 with a desired thickness by, for example, spin coating. The first photosensitive resin layer 51, that is, the resin for the partition wall, is a positive resist. Also, in this example, in step S3, a photosensitive resin for the upper lid is coated on the first photosensitive resin layer 51 to form a second photosensitive resin layer 52. The second photosensitive resin layer 52, that is, the resin for the upper lid, is a positive resist. That is, in this example, a positive resist is used as the photosensitive resin for the partition wall and the photosensitive resin for the upper lid. In this example, as the photosensitive resin for the upper lid for forming the second photosensitive resin layer 52, a resin having a lower exposure sensitivity (C / cm 2 ) than the photosensitive resin for the partition wall for forming the first photosensitive resin layer 51 is used. The second photosensitive resin layer 52 is coated on the first photosensitive resin layer 51 with a desired thickness by spin coating in the same manner as the first photosensitive resin layer 51. For example, a chemically amplified resist may be used as the resin for the partition wall for forming the first photosensitive resin layer 51, and a non-chemically amplified resist may be used as the resin for the upper lid for forming the second photosensitive resin layer 52.

[0068] Also, in this example, in the exposure process of step S5, a flow path pattern is drawn through 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 apparatus using light with a wavelength of 350 nm or more and 400 nm or less in the ultraviolet region as a light source is used. Here, the exposure amount is set to an optimal exposure amount for the first photosensitive resin layer 51. As described above, in this example, the resin for the upper lid for forming the second photosensitive resin layer 52 has a lower exposure sensitivity than the resin for the partition wall for forming the first photosensitive resin layer 51. Therefore, in the second photosensitive resin layer 52, the reaction is not sufficient with the exposure amount adjusted to the first photosensitive resin layer 51, but there is no problem in pattern resolution. Next, in the development step S6, the exposed first photosensitive resin layer 51 and second photosensitive resin layer 52 are developed to form a flow channel pattern 53. Here, for example, an aqueous sodium carbonate solution is used as the developer by spraying. 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 for washing by spraying. As a result, a partition layer 51a is formed as shown in Figure 6(b), and the flow channel pattern 53 is defined. In this example, as described above, the second photosensitive resin layer 52 is made of a resin with lower exposure sensitivity than the first photosensitive resin layer 51. Therefore, as shown in Figure 6, the aperture width of the exposure range in the second photosensitive resin layer 52 is smaller than the aperture width of the first photosensitive resin layer 51.

[0069] Next, the microfluidic chip with the flow channel pattern 53 formed on it is subjected to the heat treatment (post-bake) of 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 top cover resin, and the top cover resin flows from the left and right partition wall layers 51a towards the center of the flow channel pattern 53. The top cover resin that has flowed from the partition wall layers 51a is bonded on the side opposite to the substrate 50, i.e., on the upper side of the flow channel pattern 53, forming the top cover layer 52a. As a result, as shown in Figure 6(c), the upper part of the flow channel pattern 53 is covered with the top cover layer 52a, the flow channel section 53a is formed, and the microfluidic chip 500 is manufactured.

[0070] In this example, the glass transition temperature (Tg) of the first photosensitive resin layer 51 that forms the partition layer 51a, i.e., the partition resin, is the same as the glass transition temperature (Tg) of the second photosensitive resin layer 52 that forms the top lid layer 52a, i.e., the top lid resin. Therefore, when the top lid 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 from positive-type resists, 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 Figure 6(b), the aperture width of the second photosensitive resin layer 52 is formed to be smaller than that of the first photosensitive resin layer 51, and the aperture width of the first photosensitive resin layer 51 is formed to be sufficiently larger than that of the second photosensitive resin layer 52. Therefore, although the width of the channel portion 53a decreases compared to the opening width of the channel pattern 53 due to the same degree of flow occurring in the first photosensitive resin layer 51 as in the second photosensitive resin layer 52, the width of the channel portion 53a is sufficiently secured as shown in Figure 6(c).

[0071] Therefore, by forming the first photosensitive resin layer 51 and the second photosensitive resin layer 52 with a positive-type resist and satisfying the condition that "exposure sensitivity of the top lid resin < exposure sensitivity of the partition resin", the top lid resin and partition resin can be flowed while maintaining sufficient flow width in the flow channel section, making it easy to form the top lid layer 52a.

[0072] (1.3.3) Formation of partition layer and upper lid layer using resins with different exposure sensitivities (2) The formation of the partition layer 11 and the top cover layer 12 when the partition resin and the top cover resin have different exposure sensitivities will be explained with reference to Figure 7. Figure 7(a) is a schematic cross-sectional view showing the first photosensitive resin layer 61 and the second photosensitive resin layer 62 formed on the substrate 60, Figure 7(b) is a schematic cross-sectional view showing the flow channel pattern on the substrate 60, and Figure 7(c) is a schematic cross-sectional view showing the general configuration of the microfluidic chip 600 according to this example. In this example, the exposure sensitivity (C / cm²) of the resin for the top cover is 2 ) is the exposure sensitivity (C / cm²) of the partition resin. 2 ) is higher than (exposure sensitivity (C / cm²) of the resin for the top cover 2Exposure sensitivity (C / cm²) of partition resin 2 This document describes a method for manufacturing a microfluidic chip under the following conditions:

[0073] As shown in Figure 7(a), in this example, in the coating process of step S1, a photosensitive resin for partitions is applied to the substrate 60 to form a first photosensitive resin layer 61. The photosensitive resin for partitions is applied to the substrate 60 to a desired thickness, for example, by spin coating. The first photosensitive resin layer 61, i.e., the partition resin, is a negative-type resist. In addition, in this example, in step S3, a photosensitive resin for the top cover is applied on top of the first photosensitive resin layer 61 to form a second photosensitive resin layer 62. The second photosensitive resin layer 62, i.e., the top cover resin, is a negative-type resist. In other words, in this example, negative-type resists are used as the photosensitive resin for partitions and the photosensitive resin for the top cover. In this example, the photosensitive resin for the top lid that forms the second photosensitive resin layer 52 has a higher exposure sensitivity (C / cm²) than the photosensitive resin for the partition that forms the first photosensitive resin layer 51. 2 A resin with low ) is used. The second photosensitive resin layer 52 is applied to the first photosensitive resin layer 51 to a desired thickness 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 lid resin for forming the second photosensitive resin layer 62.

[0074] In this example, in the exposure step S5 described above, a channel pattern is drawn on the first photosensitive resin layer 61 and the second photosensitive resin layer 62 coated on the substrate 60 via a photomask. For example, in this example, a proximity exposure apparatus is used that uses light with a wavelength of 350 nm to 400 nm, which is in the ultraviolet region, as the light source. Here, the exposure amount is set to the optimal amount for the first photosensitive resin layer 61. As described above, in this example, the resin for the top cover that forms the second photosensitive resin layer 62 has a higher exposure sensitivity than the resin for the partition wall that forms the first photosensitive resin layer 61. Therefore, the exposure amount for the second photosensitive resin layer 62 that is the same as that for the first photosensitive resin layer 61 is sufficient. Next, in the development step S6, the exposed first photosensitive resin layer 61 and second photosensitive resin layer 62 are developed to form a flow channel pattern 63. Here, for example, an aqueous sodium carbonate solution is used as the developer by spraying. 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 for washing by spraying. As a result, a partition layer 61a is formed as shown in Figure 7(b), and the flow channel 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 Figure 7(b), the area of ​​the second photosensitive resin layer 62 that remains as a pattern in the exposed area after exposure is wider than that of the first photosensitive resin layer 61. As a result, as shown in Figure 6, the aperture width of the exposed area in the second photosensitive resin layer 62 is smaller than the aperture width of the first photosensitive resin layer 61.

[0075] Next, the microfluidic chip with the flow channel pattern 63 formed on it is subjected to the heat treatment (post-bake) of 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 top cover resin, and the top cover resin flows from the left and right partition wall layers 61a towards the center of the flow channel pattern 63. The top cover resin that has flowed from the partition wall layers 61a is bonded on the side opposite to the substrate 60, i.e., on the upper side of the flow channel pattern 63, forming the top cover layer 62a. As a result, as shown in Figure 7(c), the upper part of the flow channel pattern 63 is covered with the top cover layer 62a, the flow channel section 63a is formed, and the microfluidic chip 600 is manufactured.

[0076] In this example, similar to the microfluidic chip 500 described above, in the microfluidic chip 600, the glass transition temperature (Tg) of the first photosensitive resin layer 61 that forms the partition layer 61a, i.e., the partition resin, is the same as the glass transition temperature (Tg) of the second photosensitive resin layer 62 that forms 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 negative-type 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 Figure 6(b), the aperture width of the second photosensitive resin layer 62 is formed to be smaller than that of the first photosensitive resin layer 61, and the aperture width of the first photosensitive resin layer 51 is formed to be sufficiently larger than that of the second photosensitive resin layer 52. Therefore, although the width of the channel portion 63a decreases compared to the opening width of the channel pattern 63 due to the same degree of flow occurring in the first photosensitive resin layer 61 as in the second photosensitive resin layer 62, the width of the channel portion 63a is sufficiently secured as shown in Figure 7(c).

[0077] Therefore, by forming the first photosensitive resin layer 61 and the second photosensitive resin layer 62 with a negative-type resist and satisfying the condition that "exposure sensitivity of the top lid resin > exposure sensitivity of the partition resin", the top lid resin and partition resin can be flowed while sufficiently maintaining the flow width of the flow channel to easily form the top lid layer 62a.

[0078] The above describes an example in which the partition layer and the top cover layer are formed separately (multilayer structure) in a microfluidic chip according to this embodiment. As described above, according to the manufacturing method of this embodiment, the cover material (top cover layer) that covers the channel portion of the microfluidic chip can be formed within the scope of existing photolithography processes without using an intermediate layer such as an adhesive. This prevents the elution of adhesive components into the channel and suppresses inhibition of the reaction of the solution in the channel. Furthermore, it prevents quality degradation due to bonding defects caused by uneven adhesive film thickness. It also simplifies the manufacturing process compared to joining the partition layer and the top lid layer using an intermediate component such as an adhesive.

[0079] This disclosure is not limited thereto, and the partition layer and the top lid layer may be composed of three or more layers. In this case, the second photosensitive resin layer forming the top lid layer may also be a multi-layer structure. Photosensitive resins that have thermal fluidity have the property that the fluidity of the resin increases with heat treatment as they are in the upper layers. For this reason, when the top lid layer is formed by a multi-layer structure of the second photosensitive resin layer, the upper layers bond faster than the lower layers. Therefore, in a top lid layer made of a multi-layer structure of the second photosensitive resin layer, the opening width becomes narrower as the layers get higher, and the bonding occurs at the top layer or a layer adjacent to the top layer.

[0080] (1.3.4) Formation of air bubble removal section in the upper lid layer In the manufacturing method of the microfluidic chip 1 according to this embodiment, the bubble removal section 7 is formed at the same time as the upper lid layer 12. The formation of the bubble removal section 7 will be explained below with reference to Figures 8 and 9.

[0081] Figure 8(a) is a schematic plan view of the flow path pattern 73a before the heat treatment (post-bake) in step S8, that is, after washing the developer solution in step S7. Figure 8(b) is a schematic cross-sectional view showing the substrate 70 and partition layer 71 that define the flow path pattern 73a along the DD line in Figure 8(a), and the second photosensitive resin layer 72a on the partition layer 71. Figure 8(c) is a schematic cross-sectional view showing the substrate 70 and partition layer 71 that define the flow path pattern 73a along the EE line in Figure 8(a), and the second photosensitive resin layer 72a on the partition layer 71. As shown in Figures 8(b) and 8(c), the flow path pattern 73a defined by the substrate 70 is the space that becomes the flow path portion through which fluid flows in the microfluidic chip.

[0082] As shown in Figures 8(a) to 8(c), a second photosensitive resin layer 72a for forming the upper lid layer 72, which will be described later, is placed on top of the channel pattern 73a before post-baking. More specifically, a partition layer 71 is formed on the substrate 70, and the second photosensitive resin layer 72a remains on top of it. As shown in Figures 8(a) to 8(c), a region 74a is formed in the second photosensitive resin layer 72a above the flow channel pattern 73a for forming through holes that constitute the bubble removal section. Region 74a is formed, for example, by controlling the exposure pattern when drawing the flow channel pattern. The opening width L1 in region 74a is initially formed to be wider than the opening width L2 outside of region 74a. The opening widths L1 and L2 can be adjusted as appropriate by the difference in characteristics (high or low glass transition temperature and difference in exposure sensitivity) between the resin for the partition layer forming the partition layer 71 and the resin for the top cover forming the second photosensitive resin layer 72a, and by the photomask (exposure pattern) used to draw the flow channel pattern.

[0083] Figure 9(a) is a schematic plan view of a microfluidic chip 700 fabricated by performing the heat treatment (post-bake) of step S8 on the flow path pattern 73a shown in Figures 8(a) to 8(c). Figure 9(b) is a schematic cross-sectional view of the microfluidic chip 700 cut along line DD in Figure 9(a), and Figure 9(c) is a schematic cross-sectional view of the microfluidic chip 700 cut along line EE in Figure 9(a).

[0084] In the microfluidic chip 700, a bubble removal section 7 is formed by post-baking in the area corresponding to region 74a in Figure 8(a). More specifically, post-baking promotes the flow of the second photosensitive resin layer 72a on the opposing left and right partition wall layers 71, and as shown in Figure 9(b), it joins at the upper part near the center of the flow channel section 73. This forms the upper cover layer 72. On the other hand, in the region 74a (see Figure 8(a)) where a wide opening width L1 is provided in advance, the second photosensitive resin layer 72a is not completely bonded and a gap is maintained. As a result, through holes 74 are formed, as shown in Figure 9(c). In this way, a bubble removal section 7 having two through holes 74 is formed in the upper cover layer 72. In this example, the through holes 74 of the bubble removal section 7 in the upper cover layer 72 are formed with circular (more specifically, elliptical) opening ends in a plan view. The shape of the opening ends can be appropriately controlled by the shape of the exposure pattern (photomask).

[0085] Thus, in this embodiment, by adjusting the opening width of the resin layer for the top cover layer (second photosensitive resin layer 72a) above the flow channel pattern 73a in advance, through holes (through holes 74 in this example) that constitute the bubble removal section 7 can be formed. In other words, during the heat treatment of step S8 in which the top cover layer (top cover layer 72 in this example) is formed, the bubble removal section 7 can be easily formed at the same time as the top cover layer. That is, the top cover of the microfluidic chip 700 and multiple through holes for bubble removal can be formed within the scope of existing photolithography processes. Therefore, the manufacturing method can be simplified compared to, for example, a case where a bubble removal structure formed from a separate component from the upper lid layer is bonded together with an adhesive. Furthermore, no adhesive is used to form the bubble removal section 7. This prevents the elution of adhesive components into the flow channel and suppresses inhibition of the reaction of the solution in the flow channel.

[0086] In this embodiment, the microfluidic chips 400, 500, 600, and 700 have the same configuration as the microfluidic chip 1. Furthermore, the substrates 40, 50, 60, and 70 in these microfluidic chips are equivalent to the substrate 10, the partition layers 41a, 51a, 61a, and 71 are equivalent to the partition layer 11, the top cover layers 42a, 52a, 62a, and 72 are equivalent to the top cover layer 12, and the flow channels 43a, 53a, 63a, and 73 are equivalent to the flow channel 3.

[0087] (1.4) Effects of the first embodiment The microfluidic chip 1 described above has the following effects. Microfluidic chip 1, (1) The microfluidic chip 1 according to this embodiment comprises a substrate 10, a partition layer 11 that forms a flow channel 3 on the substrate 10, and an upper cover layer 12 formed on the side of the partition layer 11 opposite to the substrate 10 and serving as a cover for the flow channel 3. The upper cover layer 12 is provided with a bubble removal section 7 which is part of the upper cover layer 12 and removes bubbles generated in the flow channel 3, and there is no adhesive layer between the partition layer 11 and the upper cover layer 12. This allows for the removal of air bubbles generated within the microchannels and prevents the elution of adhesive components into the channels, thereby suppressing inhibition of the reaction of the solution within the channels. Furthermore, it can prevent bonding defects caused by uneven adhesive film thickness. (2) The microfluidic chip 1 according to this embodiment also comprises a substrate 10, a partition layer 11 that forms a fluid channel 3 on the substrate 10, and an upper cover layer 12 formed on the side of the partition layer 11 opposite to the substrate 10 and serving as a cover for the fluid channel 3. The upper cover layer 12 is provided with a bubble removal section 7 which is part of the upper cover layer 12 and removes bubbles generated in the fluid channel 3, and the upper cover layer 12 and the partition layer 11 are welded to each other. This allows for the removal of air bubbles generated within the microchannels and prevents the elution of adhesive components into the channels, thereby suppressing inhibition of the reaction of the solution within the channels. Furthermore, it can prevent bonding defects caused by uneven adhesive film thickness. (3) The microfluidic chip 1 according to this embodiment is a microfluidic chip comprising a channel section 3 and an upper cover layer 12 that serves as a cover for the channel section 3, wherein the material of the upper cover layer 12 is a thermally fluid resin, and the upper cover layer 12 is provided with a bubble removal section 7 which is part of the upper cover layer 12 and removes bubbles generated in the channel section 3. This makes it possible to remove air bubbles that form in the microchannels and prevent the elution of adhesive components into the channels, thereby suppressing inhibition of the reaction of the solution in the channels. Furthermore, since the top lid layer 12 and the partition wall layer 11 can be joined within the scope of existing photolithography processes, bonding defects caused by uneven adhesive film thickness can also be prevented.

[0088] (4) In addition, in the microfluidic chip 1 according to this embodiment, the bubble removal section 7 may be provided in the region of the upper cover layer 12 facing the fluid channel section 3, along the direction of travel of the fluid channel section 3. This allows for the efficient removal of air bubbles that form within the microchannel. (5) In addition, in the microfluidic chip 1 according to this embodiment, the bubble removal section 7 may have a through hole 17 that penetrates the upper cover layer 12 in the thickness direction. This allows for more reliable removal of air bubbles that form within the microchannel.

[0089] (6) In addition, in the microfluidic chip 1 according to this embodiment, the shape of the opening end of the through hole 17 may be circular in plan view, and the diameter of the opening end of the through hole 17 may be in the range of 1 μm or more and 100 μm or less. This makes it possible to remove air bubbles without causing liquid leakage from the flow path section 3. (7) In addition, in the microfluidic chip 1 according to this embodiment, the shape of the opening end of the through hole 17 may be polygonal in plan view, and the longitudinal width of the opening end of the through hole 17 may be in the range of 1 μm or more and 100 μm or less. This makes it possible to remove air bubbles without causing liquid leakage from the flow path section 3. (8) In addition, in the microfluidic chip 1 according to this embodiment, the bubble removal section 7 has a plurality of through holes 17, and the spacing S of the plurality of through holes 17 may be within the range of 5 μm or more and 1000 μm or less. This allows for more efficient removal of air bubbles generated within the flow channel section 3.

[0090] (9) In addition, in the microfluidic chip 1 according to this embodiment, the cross-sectional shape of the fluid channel 3 may be rounded. This stabilizes the fluid delivery rate and flow rate (e.g., reaction solution) in the flow path section 3, and suppresses the accumulation of the substance to be inspected in the corners. (10) In addition, in the microfluidic chip 1 according to this embodiment, the top cover portion may be separate from the partition portion that forms the fluid channel. This allows for the selection of a resin with properties suitable for use as a top lid. (11) In addition, in the microfluidic chip 1 according to this embodiment, the partition layer 11 and the upper cover layer 12 that form the fluid channel 3 are made of a resin material, and the resin material may be a photosensitive resin that is photosensitive to light with wavelengths of 190 nm to 400 nm, which are in the ultraviolet light region. This allows for the formation of the lid material (upper lid layer) of the microfluidic chip by reflowing photosensitive resin without using adhesives, preventing the elution of adhesive components into the channel and suppressing inhibition of the reaction of the solution in the channel.

[0091] (12) In the microfluidic chip 1 according to this embodiment, the top cover layer 12 is separate from the partition layer 11 and may have a lower glass transition temperature than the partition layer 11. This makes it possible to suppress the occurrence of flow in the partition layer 11 and the resulting change in the flow path pattern when the upper lid layer 12 is formed. (13) In addition, in the microfluidic chip 1 according to this embodiment, the top cover layer 12 is 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 flow occurs in the resin for the partition layer when the resin material for the upper lid layer is flowed during the formation of the upper lid layer 12, the opening width of the photosensitive resin forming the partition layer 11 can be made sufficiently large, thus maintaining sufficient space as the flow channel section 3.

[0092] (14) The method for manufacturing the microfluidic chip 1 according to this embodiment also includes the steps of: coating a substrate 10 with a photosensitive resin for a partition layer 11; coating a photosensitive resin for an upper cover layer 12 on top of the coated 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 to light; developing and washing the exposed photosensitive resin for the partition layer 11 and the photosensitive resin for the upper cover layer 12 to form a partition layer 11 that defines the flow channel portion 3 on the substrate 10; and heating the photosensitive resin for the upper cover layer 12 on the partition layer 11 to make the photosensitive resin for the upper cover layer 12 flow, thereby forming an upper cover layer 12 for the flow channel portion 3 and providing through holes 17 in the upper cover layer 12 as bubble removal portions 7 for removing bubbles generated in the flow channel portion 3. This makes it possible to provide a microfluidic chip that can remove air bubbles generated in the microfluidic channel and prevent the elution of adhesive components into the channel, thereby suppressing inhibition of the reaction of the solution in the channel.

[0093] 2. Second Embodiment Hereinafter, a microfluidic chip according to the second embodiment of this disclosure will be described with reference to Figure 10. Figure 10 is a cross-sectional view illustrating one example configuration of a microfluidic chip 200 according to the second embodiment of this disclosure. The microfluidic chip 200 comprises a substrate 20, a partition layer 21 forming a channel section 23 on the substrate 20, and an upper cover layer 22 formed from a part of the partition layer 21. In other words, the partition layer 21 and the upper cover layer 22 of the microfluidic chip 200 are integrated. In this respect, it differs from the microfluidic chips 1,400, 500, 600, and 700 according to the first embodiment.

[0094] (2.1) Configuration of the microfluidic chip 200 The following description will mainly focus on the differences between the partition layer 21 and the top cover layer 22 of the microfluidic chip 200 and the partition layer 11 and top cover layer 12 of the first embodiment described above. Note that the other components (substrate 20, channel section 23, bubble removal section 170, through-hole 171) have the same configuration as the substrate 10, channel section 3, bubble removal section 7, and through-hole 17 of the microfluidic chip 1, so their description will be omitted. Furthermore, the materials for the partition layer 21 and the top cover layer 22 of the microfluidic chip 200 can be the same as those used for the partition layer 11 of the microfluidic chip 1.

[0095] Figure 10 shows an example configuration of a microfluidic chip 200 in which the partition layer 21 and the top cover layer 22 are integrated. In the microfluidic chip 200, the partition layer 21 itself becomes the top cover layer 22, which simplifies the manufacturing process.

[0096] (2.2) Method for manufacturing the microfluidic chip 200 The following describes an example of a manufacturing method for the microfluidic chip 200. In the manufacturing method for the microfluidic chip 200, step S3 (coating step of the second photosensitive resin) in the manufacturing method of the microfluidic chip 1 shown in Figure 4 can be omitted. This simplifies the manufacturing process. The manufacturing method of the microfluidic chip 200 will be explained in more detail below with reference to Figure 11.

[0097] Figure 11 is a schematic diagram showing each step of the manufacturing method for the microfluidic chip 200 according to this embodiment. In the manufacturing method for the microfluidic chip 200, the channel pattern is formed in the same manner as in steps S1, S2, S4 to S7 of the manufacturing method for the microfluidic chip 1 shown in Figure 4, except that the photosensitive resin formed on the substrate 20 is a single layer. Therefore, the explanation of each step in steps S1, S2, S4 to S7 will be omitted.

[0098] Figure 11(a) is a schematic plan view of the flow path pattern 220 during the manufacturing of the microfluidic chip 200 according to this embodiment. The partition wall layer 21 has an input section 32 for introducing liquid, a flow path section 33 through which the liquid flows, and an output section 34 for discharging 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 microfluidic chip 1 according to the first embodiment, so their description is omitted. Figure 11(b) is a cross-sectional view along the line BB in Figure 11(a). A partition layer 21 is formed on the base substrate 20. An input section 32 for introducing a fluid (e.g., reaction solution) is formed in the region surrounded by the substrate 20 and the partition layer 21. Note that, in order to introduce a fluid, an upper cover layer 22 is not formed above the input section 32.

[0099] Figure 11(c) is a cross-sectional view along the CC line in Figure 11(a). A partition layer 21 is formed on the substrate 20, which serves as the base member. A region 23a of the flow path pattern 220 that defines the fluid flow path 3 is formed in the area surrounded by the substrate 20 and the partition layer 21. The opening width of region 23a is formed to be narrower than that of the input section 32.

[0100] The formed channel pattern 220 is subjected to a heat treatment (post-bake). The heat treatment is carried out, for example, by using a hot plate or an oven. The post-bake is performed to heat the partition resin (partition layer 21) to its glass transition temperature (Tg) and to cause the partition resin to flow (reflow). This differs from the heat treatment in the manufacturing method of the microfluidic chip 1 according to the first embodiment described above. Depending on the properties of the photosensitive resin, the flow (reflow) tends to occur more easily on the side opposite to the substrate 20, i.e., the upper side of the channel pattern 220. As the upper part of the channel pattern 220 flows, the partition layers 21 join together and function as an upper cover material for the channel pattern 220, i.e., an upper cover layer 22 that covers the region 23a of the channel pattern 220. As a result, an upper cover layer 22 integrated with the partition layers 21 is formed, and the microfluidic chip 200 according to this embodiment is manufactured.

[0101] Figure 11(d) is a schematic plan view of the microfluidic chip 200 after heat treatment (post-bake). Due to the heat treatment, the partition layer 21 flows and the top cover layer 22 is formed, and the flow channel section 23 is defined as shown in Figure 11(f), which will be described later. Although not shown in Figure 11(d), the flow channel section 23 can be seen through the transparent top cover layer 22. The input section 32 and output section 34 also become smaller in size due to the flow of the partition layer 21, but since they are formed to a larger size in advance anticipating the reduction in size, they are not blocked by the top cover layer 22 and the through holes remain formed. This is also the case when manufacturing the microfluidic chip 1 according to the first embodiment described above.

[0102] Figure 11(e) is a schematic cross-sectional view of the microfluidic chip 200 along the BB line in Figure 11(d). Due to post-baking on the hot plate 25, the resin on the upper side of the partition layer 21 flows toward the center in the width direction 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 fluid is maintained.

[0103] Figure 11(f) is a schematic cross-sectional view of the microfluidic chip 200 along the CC line in Figure 11(d). Due to post-baking on the hot plate 25, the resin on the side of the partition layer 21 opposite to the substrate 20 (the upper side of the partition layer 21) flows from both sides and joins near the center in the width direction of the channel section 23 to form the upper cover layer 22. Thus, according to this embodiment, the cover material that covers the channel section of the microfluidic chip can be formed within the scope of existing photolithography processes without using adhesives. This prevents the elution of adhesive components into the channel and suppresses inhibition of the reaction of the solution in the channel. Furthermore, it is possible to prevent quality degradation due to bonding defects caused by uneven adhesive film thickness. In addition, the manufacturing method can be simplified compared to the case where the partition layer and the top lid layer are joined using an intermediate material such as an adhesive. Moreover, by integrally forming the partition layer 21 and the top lid layer 22, bonding defects can be suppressed more reliably.

[0104] (2.2.1) Formation of air bubble removal section in the upper lid layer In the microfluidic chip 200 according to this embodiment, as in the first embodiment described above, a bubble removal section is formed at the same time as the upper lid layer is formed. The formation of the bubble removal section 170 in the upper lid layer 22 will be explained below with reference to Figure 12. Figure 12(a) is a schematic plan view of the flow path pattern 220 before the heat treatment (post-bake) of step S8, that is, after washing the developer solution in step S7. As shown in Figure 12(a), in the flow path pattern 220, a region 171a for forming through holes that constitute the bubble removal section is formed in the upper part of the partition layer 21. Region 171a is formed, for example, by controlling the exposure pattern when drawing the flow path pattern. In the partition layer 21, the opening width L11 in region 171a for forming through holes that constitute the bubble removal section is formed to be wider than the opening width L12 outside of region 171a.

[0105] Figure 12(b) is a schematic plan view of the microfluidic chip 200 fabricated by performing the heat treatment (post-bake) of step S8 on the flow channel pattern 220. As shown in Figure 12(b), the post-bake process forms an upper cover layer 22 and a bubble removal section 170 on the microfluidic chip 200.

[0106] Specifically, in the microfluidic chip 200, post-baking causes the resin on the upper side of the opposing left and right partition wall layers 21 to flow toward the center in the width direction of the region 23a which will become the flow channel 23, and joins at the upper part near the center of the flow channel 73 in region 23a. This forms the top cover layer 22. At this time, in the region 171a (see Figure 12(a)) which has a wide opening width L11 provided in advance, the resin on the upper part of the partition wall layer 21 does not join completely and a gap is maintained. As a result, two through holes 171 are formed as shown in Figure 12(b). In this way, a bubble removal section 170 having through holes 171 is formed in the top cover layer 22.

[0107] Thus, in this embodiment, by adjusting the opening width at the top of the partition layer 21 of the flow channel pattern 220 in advance, through-holes (through-holes 171 in this example) that constitute the bubble removal section 170 can be formed. In other words, during the heat treatment in step S8, in which the top of the partition layer 21 is flowed to form the top lid layer (top lid layer 22 in this example), the bubble removal section 170 can be easily formed at the same time as the top lid layer. That is, the top lid of the microfluidic chip 200 and multiple through-holes for bubble removal can be formed within the scope of existing photolithography processes. Therefore, the manufacturing method can be simplified compared to a case where a bubble removal structure, formed from a separate component from the partition layer 21 that forms the upper lid layer 22, is bonded together with an adhesive. Furthermore, no adhesive is used to form the bubble removal section 170. This prevents the elution of adhesive components into the flow channel and suppresses inhibition of the reaction of the solution in the flow channel.

[0108] As described above, the manufacturing method of the microfluidic chip 200 according to this embodiment includes the steps of: coating a partition resin onto a substrate 10 (step S1 above); exposing the partition resin (step S5 above); developing and washing the exposed partition resin to form a partition layer 21 that defines the flow channel portion 23 on the substrate 20 (steps S6 and S7 above); and forming an upper cover layer 22 by heat-treating the partition layer 21 to cause the partition resin to flow, and providing through holes 171 in the upper cover layer 22 as bubble removal portions 170 for removing bubbles generated in the flow channel portion 23. This allows for the formation of an upper lid layer 22 that is integrally formed by welding to the partition layer 21 as part of the partition layer 21 without the use of adhesive, thereby preventing the elution of adhesive components into the flow channel 23 and suppressing inhibition of the reaction of the solution in the flow channel.

[0109] 3. Third Embodiment Hereinafter, a microfluidic chip according to the third embodiment of this disclosure will be described with reference to Figures 13 and 14. Figure 13 is a cross-sectional view illustrating one example configuration of a microfluidic chip 300 according to the third embodiment of this disclosure. The microfluidic chip 300 comprises a substrate 30, a partition wall layer 11 forming a channel section 33 on the substrate 30, and an upper cover layer 12. In other words, the microfluidic chip 300 differs from the microfluidic chips 1,400, 500, 600, 700 according to the first embodiment and the microfluidic chip 200 according to the second embodiment in that it comprises a substrate 30 and a channel section 33 formed on the substrate 30.

[0110] (3.1) Configuration of the microfluidic chip 300 The following description will mainly focus on the differences between the substrate 30 and the channel section 33 of the microfluidic chip 300 and the substrate 10 and channel section 3 of the first embodiment described above. Note that the other components of the microfluidic chip 300 (partition layer 11, top cover layer 12, bubble removal section 7, through-hole 17) are the same as those of the microfluidic chip 1, so their description will be omitted. Furthermore, the substrate 30 of the microfluidic chip 300 can be made of the same material as the substrate 10 of the microfluidic chip 1.

[0111] Figure 13 is a schematic cross-sectional view showing one example configuration of the microfluidic chip 300. As shown in Figure 13, in the microfluidic chip 300 according to this embodiment, the substrate (an example of the base) 30 has surface modification in the region facing the through-hole 17 of the bubble removal section 7. That is, the substrate 30 has a surface modification section 301 in the region of the surface 30a on the partition wall layer 11 side that faces the through-hole 17 (the region directly below the through-hole 17). The surface modification section 301 may also be called a surface modification region. By having the surface modification section 301, the microfluidic chip 300 according to this embodiment can prevent the elution of adhesive components into the channel, suppress the inhibition of the reaction of the solution in the channel, and improve the efficiency of bubble removal. The surface-modified portion 301 has its wettability modified and is given hydrophilicity by the surface modification treatment. In other words, the substrate (an example of the base portion) 30 has hydrophilicity in the region facing the through-hole 17 of the bubble removal portion 7. That is, the surface-modified portion 301 has higher wettability than other regions of the substrate 30 that constitute the flow channel portion 33, as well as the flow channel side surface 11a of the partition wall layer 11 and the flow channel side surface 12a of the top cover layer 12. As a result, the microfluidic chip 300 can more reliably improve the efficiency of bubble removal.

[0112] Surface modification refers to a process that adds new functionality to a material's properties by applying a special treatment to its surface to alter its composition and structure. For example, ultraviolet (UV) irradiation is used as a surface modification treatment (hydrophilization treatment) to impart hydrophilicity to the surface modified portion 301. UV treatment uses relatively inexpensive equipment, and the energy of ultraviolet light emitted from a low-pressure mercury lamp as a light source, along with the ozone generated by that energy, can remove (clean) organic coatings from the material surface (in this example, surface 30a) and form silanol groups (Si-OH groups) on the material surface, thereby achieving hydrophilicity of the surface to be modified.

[0113] Furthermore, in this embodiment, the surface modification treatment for forming the surface modified portion 301 is not limited to ultraviolet treatment, but may also be a plasma treatment, for example, by irradiating with plasma (atmospheric pressure, vacuum, oxygen). Hydrophilicity can also be imparted (hydrophilized) to the surface to be modified by plasma treatment. In Figure 13, for ease of understanding, the widths of the opening ends 17a and 17b of the through hole 17 are shown to be the same as the width of the surface modified portion 301. However, depending on the conditions and environment of the UV treatment and plasma treatment, the maximum width of the surface modified portion 301 does not necessarily match the width of the opening ends 17a and 17b. For example, the maximum width of the surface modified portion 301 may be slightly wider than the width of the opening ends 17a and 17b.

[0114] Bubbles trapped in the fluid (e.g., reaction solution) flowing through a microchannel can inhibit the reaction of the reaction solution or cause instability in fluid delivery due to the stagnation of the reaction solution within the microchannel. Therefore, as mentioned above, removing bubbles from the fluid in a microchannel is an important challenge in microfluidic devices. One effective method for efficiently removing bubbles from a fluid in a microchannel is to make the surface of the component with the bubble removal section (e.g., the lid material of the microchannel) on the channel side hydrophobic (water-repellent). One possible method is to change the surface of the component on the upper side of the microchannel to a hydrophobic material. However, if the constituent material of the components constituting the microchannel is changed to a hydrophobic material, effects such as poor fluid flow in the microchannel may occur over a wide area. Therefore, it is desirable to apply the effect of improving the efficiency of bubble removal only to the area around the bubble removal section.

[0115] Therefore, the inventors of the present invention focused on the fact that by imparting hydrophilicity to the region facing the bubble removal section on the bottom surface of the microchannel (the surface on the channel side of the component at the bottom of the channel), the region surrounding the bubble removal section on the top surface of the microchannel (the surface on the channel side of the component having the bubble removal section) becomes relatively hydrophobic, thereby increasing the efficiency of bubble removal.

[0116] If the bottom surface of a microchannel is hydrophilic (highly wettable), the fluid flowing through the microchannel (for example, a liquid mainly composed of water, such as a reaction solution or culture medium) will have a high affinity for the hydrophilic bottom surface and a relatively low affinity for the hydrophobic top surface. On the other hand, bubbles trapped in the fluid have a lower affinity to the bottom region of the microchannel facing the bubble removal section, while their affinity to the surrounding region of the bubble removal section on the upper surface of the microchannel increases. As a result, in the region near the bubble removal section within the microchannel, the fluid flowing through the microchannel and the bubbles trapped in the fluid are efficiently separated, allowing for more effective bubble removal.

[0117] Specifically, in the microfluidic chip 300 according to this embodiment, hydrophilicity is imparted to the region facing the through-hole 17 of the bubble removal section 7 provided in the upper lid layer 12, so that the region around the through-hole 17 on the flow channel side surface 12a of the upper lid layer 12 becomes relatively hydrophobic. In other words, in the flow channel section 33, a region with high wettability (surface modified section 301) and a region with low wettability (surface 12a in the region around the through-hole 17) are provided at opposing positions. As a result, a difference in wettability occurs in the region between the surface modified section 301 and the through-hole 17 within the flow channel section 33. This allows the microfluidic chip 300 to further improve the efficiency of bubble removal.

[0118] More specifically, the fluid flowing through the channel section 33 has a high affinity with the surface-modified portion 301 of the substrate 30, which is hydrophilic as described above, and a relatively low affinity with the surface 12a in the area surrounding the through-hole 17, which is hydrophobic. As a result, within the channel section 33, the fluid is pushed towards the surface-modified portion 301, which is hydrophilic (highly wettable). In contrast, bubbles trapped in the fluid have a lower affinity for the hydrophilic surface modification portion 301 and a higher affinity for the surface 12a in the area surrounding the through-hole 17. Therefore, contrary to the fluid that is concentrated on the surface modification portion 301 side, the bubbles in the fluid move towards the surface 12a side opposite the surface modification portion 301. As a result, the fluid and bubbles are efficiently separated in the region between the surface modification portion 301 and the through-hole 17 of the flow channel 33, and the removal of bubbles from the through-hole 17 is performed more effectively.

[0119] Furthermore, since the surface 12a around the through-hole 17 facing the surface-modified portion 301 of the substrate 30 is relatively hydrophobic, bubbles that move from the fluid to the area around the through-hole 17 are more likely to burst. This improves the efficiency of bubble removal.

[0120] (water contact angle) One indicator used to evaluate the hydrophilicity of the surface-modified portion 301 of the substrate 30 is the water contact angle. In the microfluidic chip 300 according to this embodiment, it is sufficient if the water contact angle of the surface-modified portion 301 on the surface 30a of the substrate 30 is 90 degrees or less, and more preferably 30 degrees or less. If the water contact angle is 90 degrees or less, it can be said that the surface-modified portion 301 has sufficient hydrophilicity to further improve the bubble removal effect.

[0121] Methods for controlling the water contact angle include adjusting the ultraviolet irradiation energy (unit: mJ) and the ultraviolet irradiation time. The higher the ultraviolet irradiation energy, the smaller the water contact angle of the irradiated surface (in this example, the surface modified portion 301), i.e., the more hydrophilicity can be improved. Similarly, the longer the ultraviolet irradiation time, the smaller the water contact angle of the irradiated surface (surface modified portion 301), i.e., the more hydrophilicity can be improved.

[0122] For measuring the water contact angle, for example, a contact angle meter "PCA-1" manufactured by Kyowa Interface Co., Ltd. can be used. In measurement using the above contact angle meter, water is filled into a syringe and attached to the contact angle meter, and parameters such as the waiting time until contact angle measurement [msec], measurement time interval [msec], and number of consecutive measurements [times] are set. Next, water is dropped from the syringe onto the surface of a sample having the same configuration as the substrate 30, and an image is captured and the contact angle of the droplet (static contact angle) is measured. The static contact angle measurement method employs the droplet method. The droplet method assumes that the droplet is part of a sphere, and determines the contact angle θ from the radius r and height h of the droplet after it has been dropped.

[0123] (3.2) Method for manufacturing the microfluidic chip 300 An example of a method for manufacturing the microfluidic chip 300 will be described below with reference to Figure 14. Figure 14 is a flowchart showing an example of a method for manufacturing the microfluidic chip 300 according to this embodiment. As shown in Figure 14, the method for manufacturing the microfluidic chip 300 includes, in addition to steps S1 to S8 of the method for manufacturing the microfluidic chip 1 shown in Figure 4, a step (step S9) of performing a surface modification treatment on the region of the surface 30a on the partition wall layer 11 side of the substrate 30 that faces the through hole 17. This makes it possible to provide a surface modification portion 301 on the substrate 30 in the microfluidic chip 300.

[0124] Specifically, in the manufacturing method of the microfluidic chip 300 according to this embodiment, in step S9, which is performed after the heat treatment (post-bake treatment) in step S8, a surface modification treatment is performed on the surface 30a of the substrate 30 through the through holes 17 of the upper lid layer 12 formed by the post-bake treatment. This makes it possible to obtain a microfluidic chip that can prevent the elution of adhesive components into the channels, suppress the inhibition of the reaction of the solution in the channels, and improve the efficiency of bubble removal.

[0125] Furthermore, in the manufacturing method of the microfluidic chip 300 according to this embodiment, for example, in step S9, ultraviolet treatment is performed as a surface modification treatment. More specifically, surface modification treatment (hydrophilization treatment) is performed by irradiating ultraviolet light from the through hole 17 of the upper lid layer 12 toward the region of the substrate 30 facing the through hole 17, thereby imparting hydrophilicity to that region. As a result, a surface modification portion 301 can be provided at a position facing the through hole 17. Therefore, the efficiency of bubble removal in the microfluidic chip can be improved more reliably. Furthermore, the surface modification treatment (hydrophilization treatment) in step S9 is not limited to ultraviolet treatment; plasma treatment may also be performed.

[0126] (3.3) Variant Although the microfluidic chip 300 according to this embodiment has been described above, the form of the microfluidic chip having the surface modification portion 301 is not limited thereto. For example, the height of the flow channel section 33 is not constant, and there may be variations in its height. For instance, the configuration may involve variations in the height of the partition wall layer 11, or the surface 30a of the substrate 30 may have slopes or irregularities. Normally, increasing the height (depth) of the microchannel can reduce the efficiency of bubble removal. However, by providing a hydrophilic surface modification section 301 opposite the through-hole 17 of the bubble removal section 7, the efficiency of bubble removal can be improved even in regions where the height (depth) of the channel section 33 is relatively deep.

[0127] Furthermore, for example, the flow channel section 33 may have a bent shape (a shape with corners) in a plan view. Normally, if a bent section (corner) is provided in a microchannel, the fluid delivery speed is reduced, causing fluid stagnation, which can reduce the efficiency of bubble removal. However, by providing a hydrophilic surface modification section 301 at a position opposite the through hole 17, the efficiency of bubble removal can be improved even if the flow channel section 33 has a bent section.

[0128] Furthermore, although the microfluidic chip 300 according to this embodiment is configured by providing a surface modification portion 301 to the microfluidic chip 1 according to the first embodiment, the disclosure is not limited thereto. For example, the surface modification portion 301 may be provided to the microfluidic chip 200 according to the second embodiment. This makes it possible to improve the efficiency of bubble removal even in a microfluidic chip in which the partition layer 21 and the top cover layer 22 are integrated.

[0129] (Examples)

[0130] The above-described microfluidic chip and its manufacturing method will be explained using specific examples. However, this disclosure is not limited to the following examples. <First Example> Examples of the microfluidic chip and its manufacturing method according to the first embodiment described above will be explained. First, a photosensitive resin for the partition layer was coated onto the glass substrate to form the first photosensitive resin layer. A transparent negative-type liquid resin (negative-type liquid resist) made of epoxy resin was used for the partition layer. This photosensitive resin (negative-type liquid resist) had a glass transition temperature (TG) of 160°C. The negative-type liquid resist was coated 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 was 50 μm. Next, a heat treatment (pre-bake) was performed on a hot plate to remove residual solvent contained in the photosensitive resin (negative type liquid resist) for the partition layer. The pre-bake was carried out at a temperature of 90°C for 20 minutes.

[0131] Next, a photosensitive resin for the top lid was applied to the first photosensitive resin layer to form a second photosensitive resin layer. The photosensitive resin for the top lid was the same as the negative-type 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 layer. Pre-baking was also performed under the same conditions as for the photosensitive resin for the partition layer to remove any residual solvent contained in the photosensitive resin for the top lid.

[0132] Next, the photosensitive resin layers (first photosensitive resin layer, second photosensitive resin layer) on the glass substrate were exposed to create a channel pattern. Specifically, the photosensitive resin was pattern-exposed via a photomask having a microchannel pattern arrangement. The photomask used had a two-layer structure of chromium and chromium oxide as the light-shielding film. A proximity exposure apparatus was used for exposure. The exposure apparatus used a high-pressure mercury lamp as the light source and an i-line filter cut filter for exposure. The exposure dose was 170 mJ / cm². 2 In this case, the pattern arrangement of the microchannels in the photomask also includes the pattern of the region for forming the through-holes in the bubble removal section.

[0133] Next, the exposed photosensitive resin layer was developed to form a channel pattern. Specifically, the unexposed areas were dissolved by developing the photosensitive resin layer with an alkaline developer (TMAH 2.38%) for 60 seconds, thereby patterning the channel structure. Next, the substrate was shower-washed with ultrapure water to remove the developer from the photosensitive resin layer, and then dried using a spin dryer. At this stage, the upper part of the channel pattern opposite the glass substrate is open. Also, the second photosensitive resin layer remains on the partition layer.

[0134] Next, the channel pattern was heat-treated (post-bake) in an oven at 160°C for 30 minutes. During this process, the reflow of the photosensitive resin caused the second photosensitive resin layer on the upper part of the channel pattern, i.e., on the opposing partition layers, to flow towards the center of the channel section, forming through-holes that constitute the top cover layer and the bubble removal section. This resulted in obtaining the microchannel chip according to this embodiment. At both ends of the channel section, the input and output sections, which are through-holes, were formed without being blocked by the top cover layer.

[0135] As described above, the microfluidic chip according to this embodiment has the partition layer and the top lid layer welded together without the use of adhesive, and the top lid layer is formed by the flow of the resin for the top lid layer (second photosensitive resin layer) during post-baking. This prevents the elution of adhesive components into the channel and suppresses inhibition of the reaction of the solution in the channel. Furthermore, 10 μL of the colored reaction solution was pipetted into the microfluidic chip of this embodiment and introduced through the inlet port of the channel. The flow of the solution was then observed under a microscope. The introduced reaction solution flowed smoothly through the channel without any leakage, indicating good fluid delivery. Therefore, it was confirmed that the microfluidic chip of this embodiment allows fluid to flow smoothly without leakage, and possesses the basic performance of a microfluidic chip.

[0136] Furthermore, although the reaction solution flowing through the channel contained multiple air bubbles that had been trapped during injection, it was confirmed that the bubbles were efficiently discharged to the outside through the through-holes of the bubble removal section. As a result, there were no bubbles in the solution after passing through the bubble removal section, and they did not interfere with observation. Therefore, it was confirmed that the microfluidic chip of this embodiment allows fluid to flow smoothly and has the function of efficiently removing air bubbles contained in the fluid within the channel.

[0137] <Second Example> Examples of the microfluidic chip and its manufacturing method according to the second embodiment described above will be explained. A microfluidic chip according to the second embodiment was fabricated in the same manner as the first embodiment, except that the partition layer and the top cover layer were integrally formed. Specifically, first, a photosensitive resin for the partition layer was coated onto a glass substrate to form a first photosensitive resin layer, similar to the first embodiment described above, and then a pre-baking treatment was performed. Next, the first photosensitive resin layer on the glass substrate was exposed under the same exposure conditions as in the first embodiment to draw a channel pattern.

[0138] Next, the exposed first photosensitive resin layer was developed under the same conditions as in the first embodiment, the developer was removed, and the layer was dried with a spin dryer to form a channel pattern. An example of a cross-sectional SEM image of the channel pattern at this point is shown in Figure 15(a). In Figure 15(a), the recess sandwiched between opposing partition layers corresponds to the flow path portion of the flow path pattern. As shown in Figure 15(a), in the flow path portion of the flow path pattern after the developer has been removed and dried, the upper portion opposite to the glass substrate is open. The upper opening of the flow path portion is the same as in the first embodiment described above.

[0139] Next, the channel pattern was post-baked under the same conditions as in the first embodiment (160°C in an oven for 30 minutes). During this process, the reflow of the photosensitive resin caused the photosensitive resin (negative liquid resist) on the upper part of the channel pattern, i.e., the upper part of the opposing partition layers, to flow towards the center of the channel section, forming through-holes that constitute the top cover layer and the bubble removal section. This resulted in obtaining the microfluidic chip according to this embodiment.

[0140] Figure 15(b) shows an example of a cross-sectional SEM image of a microfluidic chip after post-baking. As shown in Figure 15(b), it was confirmed that after post-baking, the photosensitive resin on the upper side of the channel pattern (i.e., the upper side of the partition layer) flowed and bonded near the center of the channel section, forming the upper lid layer. Furthermore, as shown in Figure 15(b), it was confirmed that the upper lid layer formed by the flow of the partition layer becomes thinner toward the center of the flow channel, and that a recess is formed. Also, as shown in Figure 15(b), it was confirmed that the cross-sectional shape of the flow channel is rounded. In addition, as shown in the upper center of Figure 15(b), it was confirmed that through holes constituting a locally formed bubble removal section are formed in the depth direction of the upper lid layer. These points are also the same in the first embodiment described above, in which the partition layer and the upper lid layer are separate components. Furthermore, through-holes, which are input and output sections, were formed at both ends of the flow channel section without being blocked by the top cover layer.

[0141] In the microfluidic chip fabricated according to this embodiment as described above, the top lid layer is formed by the flow of material on top of the partition layer due to post-baking, and no adhesive is used to join the partition layer and the top lid layer. This prevents the elution of adhesive components into the fluid channel and suppresses inhibition of the reaction of the solution in the fluid channel. Furthermore, a fluid delivery test was performed on the microfluidic chip of this embodiment in the same manner as in the first embodiment described above. As a result, the introduced reaction solution flowed smoothly through the channel without any obstruction, and there was no leakage from the channel, indicating good fluid delivery. Therefore, it was confirmed that the microfluidic chip of this embodiment allows fluid to flow smoothly without obstruction and does not leak, thus possessing the basic performance of a microfluidic chip.

[0142] Furthermore, although the reaction solution flowing through the channel contained multiple air bubbles that had been trapped during injection, it was confirmed that the bubbles were efficiently discharged to the outside through the through-holes of the bubble removal section. As a result, there were no bubbles in the solution after passing through the bubble removal section, and they did not interfere with observation. Therefore, it was confirmed that the microfluidic chip of this embodiment allows fluid to flow smoothly and has the function of efficiently removing air bubbles contained in the fluid within the channel.

[0143] <Third Example> Examples of the microfluidic chip and its manufacturing method according to the third embodiment described above will be explained. A microfluidic chip according to the third embodiment was fabricated in the same manner as the first embodiment, except that a surface modification treatment was performed on the microfluidic chip after post-baking. Specifically, a tabletop ozone cleaning device (OC1801C10X) was used to perform ultraviolet (UV) treatment for 5 minutes so that the integrated UV light dose reached 10,000 mJ. This formed a surface modification area on the substrate surface opposite the through-holes. At this time, UV light was irradiated onto the substrate surface through the through-holes in the top cover layer. By performing UV treatment, organic coatings can be removed (cleaned) from the irradiated surface (substrate surface) and silanol groups (Si-OH groups) can be formed, making the area on the substrate surface opposite the through-holes in the top cover layer hydrophilic. In the microfluidic chip of this embodiment, UV treatment through the through-holes allows for localized hydrophilicization of the underside of the through-holes in the bubble removal section (for example, the area directly below them). This efficiently separates the fluid flowing through the microfluidic channel from the bubbles trapped within the fluid, enabling effective bubble removal.

[0144] As described above, the microfluidic chip according to this embodiment has the partition layer and the top lid layer welded together without the use of adhesive, and the top lid layer is formed by the flow of the resin for the top lid layer (second photosensitive resin layer) during post-baking. This prevents the elution of adhesive components into the channel and suppresses inhibition of the reaction of the solution in the channel. Furthermore, a liquid delivery test was performed on the microfluidic chip of this embodiment in the same manner as in the first embodiment described above. As a result, the introduced reaction solution flowed smoothly through the channel without any obstruction, and there was no leakage from the channel, indicating good fluid delivery. Therefore, it was confirmed that the microfluidic chip of this embodiment possessed the basic performance of a microfluidic chip, with fluid flowing smoothly and without leakage.

[0145] Furthermore, although several air bubbles were present in the reaction solution flowing through the channel, it was visually confirmed that the bubbles were efficiently discharged to the outside through the through-holes of the bubble removal section. As a result, there were no bubbles in the solution after passing through the bubble removal section, and this did not interfere with observation. Therefore, it was confirmed that the microfluidic chip of this embodiment has the function of allowing fluid to flow smoothly and efficiently removing air bubbles contained in the fluid within the channel.

[0146] Furthermore, after UV treatment, the water contact angle of the surface-modified portion of the substrate surface of the microfluidic chip of this embodiment was measured. As described above, the static contact angle was measured using the droplet method with a contact angle meter "PCA-1 manufactured by Kyowa Interface Co., Ltd." In this embodiment, the water contact angle of the surface-modified portion was 10 degrees. Therefore, it was found that the microfluidic chip of this embodiment has sufficient hydrophilicity to improve the efficiency of bubble removal.

[0147] <Fourth Example> Examples of a microfluidic chip and a method for manufacturing the same, relating to a modified version of the third embodiment described above, will be explained. The microfluidic chip according to the fourth embodiment was fabricated by integrally forming the partition layer and the top lid layer, similar to the second embodiment, except that a surface modification treatment was performed on the microfluidic chip after post-baking.

[0148] Specifically, as a surface modification treatment, the microfluidic chip after post-bake treatment was subjected to ultraviolet (UV) treatment for 5 minutes using a tabletop ozone cleaning device (OC1801C10X) to achieve an integrated ultraviolet (UV) light dose of 10,000 mJ. This formed a surface modification area on the substrate surface in the region facing the through-holes of the upper cover layer. At this time, as in the third embodiment described above, ultraviolet light was irradiated onto the substrate surface through the through-holes of the upper cover layer.

[0149] Furthermore, a liquid delivery test was performed on the microfluidic chip of this embodiment in the same manner as in the first embodiment described above. As a result, the introduced reaction solution flowed smoothly through the channel without any obstruction, and there was no leakage from the channel, indicating good fluid delivery. Therefore, it was confirmed that the microfluidic chip of this embodiment possessed the basic performance of a microfluidic chip, with fluid flowing smoothly and without leakage.

[0150] Furthermore, although several air bubbles were present in the reaction solution flowing through the channel, it was visually confirmed that the bubbles were efficiently discharged to the outside through the through-holes of the bubble removal section. As a result, there were no bubbles in the solution after passing through the bubble removal section, and this did not interfere with observation. Therefore, it was confirmed that the microfluidic chip of this embodiment has the function of allowing fluid to flow smoothly and efficiently removing air bubbles contained in the fluid within the channel.

[0151] Furthermore, after UV treatment, the water contact angle of the surface-modified portion of the substrate surface of the microfluidic chip of this embodiment was measured. As described above, the static contact angle was measured using the droplet method with a contact angle meter "PCA-1 manufactured by Kyowa Interface Co., Ltd." In this embodiment, the water contact angle of the surface-modified portion was 10 degrees. Therefore, it was found that the microfluidic chip of this embodiment has sufficient hydrophilicity to improve the efficiency of bubble removal. [Industrial applicability]

[0152] This disclosure is suitably applicable to microfluidic chips for research, diagnostic, testing, analysis, and culture purposes, as it allows for the formation of a top cover without requiring complex manufacturing processes, and also serves as a method for manufacturing the same. [Explanation of symbols]

[0153] 1,200, 400, 500, 600, 700... Microfluidic chips 2, 32… Input section 3, 23, 43a, 53a, 63a, 73... Flow channel section 4, 34… Output section 7, 170... Bubble removal section 10, 20, 40, 50, 60, 70... circuit boards 11, 21, 41a, 51a, 61a, 71...Partition layer 12, 22, 42a, 52a, 62a, 72...upper lid layer 17, 74, 171… through holes 25…Hot plate

Claims

1. The base and, A partition wall portion that forms a flow path on the base, An upper cover portion is formed on the side of the partition wall portion opposite to the base portion and serves as a cover for the flow path, Equipped with, The upper cover portion is provided with a bubble removal portion which is a part of the upper cover portion and removes bubbles that form in the flow path. The bubble removal section has a through hole that penetrates the upper lid in the thickness direction, The shape of the opening end of the through hole is circular in plan view. The diameter of the opening end of the through hole is in the range of 1 μm to 100 μm. The bubble removal section has a plurality of through holes, and the spacing between the plurality of through holes is within the range of 5 μm to 1000 μm. The partition wall and the upper lid are formed of a resin material. The partition wall and the upper lid are directly joined together without an adhesive layer in between. The upper cover portion has a recess on the side opposite to the flow path and in the region that overlaps with the flow path. A microfluidic chip characterized by the following features.

2. The resin material forming the upper lid is a thermally fluid resin with a melt flow rate in the range of 1 g / 10 min to 100 g / 10 min (230°C). In the region where the recess is formed in the upper lid, the thickness decreases from the partition wall side toward the center of the flow path. The microfluidic chip according to feature 1.

3. The upper lid portion and the partition portion are formed of a photosensitive resin. The photosensitive resins forming the upper lid and the partition wall are welded together. The microfluidic chip according to feature 1 or 2.

4. The material of the upper lid is a thermally fluid resin. The microfluidic chip according to feature 3.

5. The bubble removal section is provided in the region of the upper lid facing the flow path, along the direction of the flow path. The microfluidic chip according to feature 4.

6. The base portion that constitutes the bottom surface of the flow channel has a surface modified region facing the through hole. A microfluidic chip according to any one of claims 1 to 5.

7. The base portion that constitutes the bottom surface of the aforementioned flow path has a hydrophilic region in the area facing the through hole. A microfluidic chip according to any one of claims 1 to 6.

8. The region opposite the through hole is a local region directly below the through hole, The base portion that constitutes the bottom surface of the flow channel has a localized area that has been surface-modified to be hydrophilic. The microfluidic chip according to feature 7.

9. The cross-sectional shape of the aforementioned flow path is rounded. A microfluidic chip according to any one of claims 1 to 8.

10. The aforementioned resin material is a photosensitive resin that is sensitive to light with wavelengths of 190 nm to 400 nm, which are in the ultraviolet light region. A microfluidic chip according to any one of claims 1 to 9.

11. The resin material forming the upper lid has a lower glass transition temperature than the resin material forming the partition wall. A microfluidic chip according to any one of claims 1 to 10.

12. The aforementioned resin material is a photosensitive resin, The photosensitive resin forming the upper lid has a higher or lower exposure sensitivity than the photosensitive resin forming the partition wall. A microfluidic chip according to any one of claims 1 to 11.

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