Microchannel chip and method for manufacturing the same

Abstract

To provide a microchannel chip in which a resin layer that forms a channel on a substrate and a lid material are joined together, and in which peeling between the lid material and the resin layer due to changes over time can be suppressed.SOLUTION: A microchannel chip comprises a substrate 10, a partition layer 20 provided on the substrate 10 to define a channel 3, and a lid material 30 provided on the side of the partition layer 20 opposite to the side in contact with the substrate 10, and the rubber hardness of the lid material 30 measured with a micro rubber hardness meter is 97.5 points or less.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present disclosure relates to a microchannel chip and a manufacturing method thereof. [Background technology]

[0002] In recent years, a technology has been proposed that uses lithography and thick film processing technology to form a microscopic reaction field, enabling testing with samples of a few μL to a few nL. This technology that uses a microscopic reaction field is called μ-TAS (Micro Total Analysis System). μ-TAS is applied in areas such as genetic testing, chromosome testing, cell testing, and drug development, as well as biotechnology, testing of trace substances in the environment, investigation of the breeding environment of agricultural crops, and genetic testing of agricultural crops. The introduction of μ-TAS technology can bring about great benefits such as automation, high speed, high precision, low cost, rapidity, and reduced environmental impact. μ-TAS often uses micrometer-sized flow paths (microflow paths, microchannels) formed on a substrate, and such substrates are called chips, microchips, microflow path chips, microfluidic chips, microfluidic devices, microflow path devices, etc.

[0003] Conventionally, such microchannel chips have been produced using techniques such as injection molding, molding, cutting, and etching. In addition, glass substrates are mainly used as substrates for microchannel chips because they are easy to produce and optically detectable. On the other hand, development of microchannel chips using resin materials, which are lightweight, less likely to break than glass substrates, and less expensive, is also underway. As a method for producing a microchannel chip using a resin material, there is a method in which a resin substrate having a channel pattern is formed mainly by photolithography, and a cover material is bonded to the resin substrate to produce a microchannel chip. This method makes it possible to form fine channel patterns, which was difficult to achieve with conventional techniques.

[0004] In addition, as a method for bonding the substrate side (wall portion provided on the substrate) of the microchannel chip to the lid material, a method of bonding using an adhesive (including a pressure sensitive adhesive, a sealant, a double-sided tape, a sticky tape, etc.) having a thickness of several μm to several tens of μm is relatively common (see, for example, Patent Document 1). However, when bonding using an adhesive, depending on the application of the microchannel chip, problems may arise such as elution of the adhesive components and visibility during inspection. For this reason, methods have been proposed that do not use an adhesive, but instead use pressure bonding using a heat press machine or an ultrasonic welding machine (see, for example, Patent Document 2), or that modify the surfaces of both the lid material and the wall portion bonding the lid material by converting a process gas into plasma under atmospheric pressure or a pressure close to the atmospheric pressure, and bond them (see, for example, Patent Document 3). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2003-60127 A [Patent Document 2] JP 2002-139419 A [Patent Document 3] JP 2011-104886 A Summary of the Invention [Problem to be solved by the invention]

[0006] When manufacturing a microchannel chip, if a resin layer (wall) that forms a channel pattern on a substrate and a lid material are bonded together without using an adhesive, the lid material and the microchannel substrate may peel off over time after bonding (lamination). If peeling occurs immediately after bonding, it is clear that the chip cannot be used as a microchannel chip, and it is not shipped. However, if peeling occurs, for example, after a certain period of time (e.g., one week) has passed since manufacture, various problems may occur. For example, a microfluidic chip may be shipped or delivered, but be recognized as defective by the recipient. In this case, it takes time to discover the defect (confirmation of peeling), and it also takes time to recover from the situation, which can lead to problems such as compensation to the recipient. Furthermore, for example, if detachment occurs when testing a specimen (fluid) using the microchannel chip, the fluid will leak out of the microchannel chip. Many of the fluids handled by microchannel chips are body fluids (blood, etc.) containing bacteria, viruses, and pathogens, or antibacterial drugs used to test the effects of these drugs, so preventing leakage of fluids out of the chip is important from the viewpoint of biosafety as well.

[0007] In order to prevent such defects (peeling, poor bonding), generally, the conditions for surface modification of the contact surface between the lid material and the resin layer before bonding, and bonding conditions such as the temperature, pressure, and time of the heat press during thermocompression bonding are appropriately set according to the materials used for the lid material and the microchannel substrate (particularly the resin layer). However, conventional techniques have not been able to sufficiently prevent peeling between the lid material and the resin layer on the substrate side due to changes over time.

[0008] In view of the above problems, the present disclosure aims to provide a micro-channel chip in which a resin layer that forms a channel on a substrate and a lid material are bonded together, and which is capable of suppressing peeling between the lid material and the resin layer due to changes over time, and a method for manufacturing the same. [Means for solving the problem]

[0009] A microchannel chip according to one embodiment of the present disclosure comprises a substrate, a partition layer provided on the substrate to define a channel, and a cover material provided on a surface of the partition layer opposite to a surface that contacts the substrate, wherein the rubber hardness of the cover material measured with a micro rubber hardness tester is 97.5 points or less. A microchannel chip according to another embodiment of the present disclosure comprises a substrate, a partition layer provided on the substrate to define a channel, and a lid material provided on a surface of the partition layer opposite to a surface in contact with the substrate, the lid material being made of a resin material, and the resin material having a composite elastic modulus of 2.5 GPa or less as measured by a nanoindentation method. A micro-channel chip according to still another embodiment of the present disclosure comprises a substrate, a partition layer provided on the substrate to define a channel, and a cover material provided on a surface of the partition layer opposite to a surface that contacts the substrate, wherein the micro-channel chip after bonding the cover material and the partition layer has a flatness of 6.5 μm or less in PV value in any 10 mm square area.

[0010] A method for manufacturing a microchannel chip according to one embodiment of the present disclosure includes the steps of applying a photosensitive resin onto a substrate, exposing the applied photosensitive resin to light, developing the exposed photosensitive resin and rinsing with pure water to form a partition layer that defines a channel on the substrate, and bonding a lid material to a surface of the partition layer opposite to a surface that contacts the substrate, wherein the rubber hardness of the lid material measured with a micro rubber hardness tester is 97.5 points or less. A method for manufacturing a microchannel chip according to another aspect of the present disclosure includes the steps of applying a photosensitive resin onto a substrate, exposing the applied photosensitive resin to light, developing the exposed photosensitive resin and rinsing with pure water to form a partition layer that defines a channel on the substrate, and bonding a lid material made of a resin material to a surface of the partition layer opposite to a surface that contacts the substrate, wherein the composite elastic modulus of the resin material constituting the lid material is 2.5 GPa or less as measured by a nanoindentation method. A method for manufacturing a micro-channel chip according to still another aspect of the present disclosure includes the steps of applying a photosensitive resin onto a substrate, exposing the applied photosensitive resin to light, developing the exposed photosensitive resin and rinsing it with pure water to form a partition layer that defines a channel on the substrate, and bonding a lid material to a surface of the partition layer opposite to a surface that contacts the substrate, wherein the micro-channel chip after the lid material is bonded to the partition layer has a flatness of 6.5 μm or less in PV value in any 10 mm square area. Effect of the Invention

[0011] According to the present disclosure, it is possible to provide a micro-channel chip in which a resin layer that forms a channel on a substrate and a lid material are bonded together, and which is capable of suppressing peeling between the lid material and the resin layer due to changes over time. [Brief description of the drawings]

[0012] [Figure 1] FIG. 1 is a plan view illustrating a structure of a micro-channel chip according to first to third embodiments. [Diagram 2] 1 is a cross-sectional view illustrating a structure of a micro-channel chip according to first to third embodiments. [Diagram 3] 1A to 1C are diagrams illustrating a manufacturing method of the micro-channel chip according to the first to third embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] An embodiment of the present disclosure will be described. Note that this embodiment shows an example of the present disclosure, and the present disclosure is not limited to this embodiment. In addition, various modifications or improvements can be made to this embodiment, and such modifications or improvements can also be included in the present disclosure.

[0014] As a result of intensive research, the present inventors have found that in a microchannel chip in which a resin layer (hereinafter sometimes referred to as a "partition layer") that defines a channel on a substrate is bonded to a cover material, the hardness of the cover material is important in order to prevent peeling between the cover material and the partition layer due to changes over time after bonding between the cover material and the partition layer. Examples of indicators of the hardness of a cover material include rubber hardness and composite elastic modulus.

[0015] When a heat press is used to bond the lid material and the partition layer (thermocompression bonding), there is a thermal history of returning to room temperature after bonding at a high temperature. When a resin material is used for the lid material and an inorganic material such as glass is used for the substrate on which the partition layer (resin layer) is provided, the thermal expansion coefficients of the lid material and the substrate are significantly different. In general, the thermal expansion coefficient of the resin material is larger by about one to two orders of magnitude than that of the inorganic material. That is, the amount of contraction when returning from a high temperature state during bonding to room temperature is larger for the lid material (resin material) than for the substrate (inorganic material). As a result, internal stress is generated in the resin material forming the lid material. As a result, shear stress (=shear stress) is generated on the bonding surface (lamination surface) between the partition layer, which is a resin layer on the substrate (inorganic material), and the lid material, and it is considered that peeling occurs between the partition layer and the lid material when the shear stress exceeds the shear peel strength of the bonding surface.

[0016] As shown in the following formula, the shear stress τ at the above-mentioned joint surface is proportional to the internal stress σ of the lid material and the cross-sectional area S of the lid material, and the internal stress σ is expressed as the product of the elastic modulus E of the lid material and the strain ε of the lid material. τ (shear stress) = F (force parallel to the joint surface) / A (area of ​​the joint surface) = σ (stress parallel to the joint surface) S (cross-sectional area of ​​the lid material) / A (area of ​​the joint surface) = E (elastic modulus of the lid material) ε (strain parallel to the joint surface of the lid material) S (cross-sectional area of ​​the lid material) / A (area of ​​the joint surface) (Equation 1)

[0017] In other words, it can be seen that the shear stress τ generated at the joint surface between the partition layer and the lid material is proportional to the elastic modulus E of the lid material, the strain ε of the lid material, and the cross-sectional area S of the lid material. In addition, since the strain ε of the lid material is proportional to the difference between the thermal expansion coefficient of the substrate (inorganic material) and the thermal expansion coefficient of the lid material, it is possible to reduce the shear stress and suppress the occurrence of peeling by using a lid material that satisfies the following conditions: (1) a material with a small thermal expansion coefficient (close to the thermal expansion coefficient of the substrate), (2) a resin material with a small elastic modulus, and (3) a small cross-sectional area (thin thickness).

[0018] However, it may be difficult to reduce the thickness of the lid material (reduce the cross-sectional area) depending on the specifications of the microchannel chip according to the application (e.g., a certain thickness is required to inject a sample) and the molding method of the lid material. Therefore, the inventors focused on the hardness index of the lid material (rubber hardness, composite elastic modulus) which is related to the internal stress σ of the lid material, and discovered that by ensuring that the hardness index meets certain conditions, it is possible to suppress peeling between the lid material and the partition layer due to changes over time after bonding.

[0019] The inventors also considered that the amount of warping (flatness) of the micro-channel chip immediately after bonding of the lid material during production of the micro-channel chip represents the magnitude of the internal stress σ remaining in the lid material, in other words, it is an index representing the magnitude of the shear stress at the bonding surface between the partition layer and the lid material, and found that peeling between the lid material and the partition layer due to changes over time can be suppressed by making the above-mentioned amount of warping (flatness) of the micro-channel chip immediately after bonding of the lid material satisfy certain conditions.

[0020] That is, a first embodiment of a microchannel chip according to the present disclosure comprises a substrate, a partition layer provided on the substrate to define a channel, and a cover material provided on the surface of the partition layer opposite to the surface that contacts the substrate, and the rubber hardness of the cover material measured with a micro rubber hardness tester is 97.5 points or less. A second embodiment of a microchannel chip according to the present disclosure comprises a substrate, a partition layer provided on the substrate to define a channel, and a lid material provided on a surface of the partition layer opposite to a surface in contact with the substrate, the lid material being made of a resin material, and the composite elastic modulus of the resin material measured by nanoindentation is 2.5 GPa or less.

[0021] A third embodiment of a micro-channel chip according to the present disclosure comprises a substrate, a partition layer provided on the substrate to define a channel, and a lid material provided on the surface of the partition layer opposite to the surface that contacts the substrate, and the micro-channel chip after bonding the lid material and the partition layer has a flatness of 6.5 μm or less in PV value in any 10 mm square area.

[0022] Furthermore, a first embodiment of a method for manufacturing a microchannel chip according to the present disclosure includes the steps of applying a photosensitive resin onto a substrate, exposing the applied photosensitive resin to light, developing the exposed photosensitive resin and rinsing with pure water to form a partition layer that defines a channel on the substrate, and bonding a lid material to a surface of the partition layer opposite to the surface that contacts the substrate, wherein the rubber hardness of the lid material measured with a micro rubber hardness tester is 97.5 points or less. A second embodiment of the method for manufacturing a microchannel chip according to the present disclosure includes the steps of applying a photosensitive resin onto a substrate, exposing the applied photosensitive resin to light, developing the exposed photosensitive resin and rinsing it with pure water to form a partition layer that defines a channel on the substrate, and bonding a lid material made of a resin material to a surface of the partition layer opposite to the surface that contacts the substrate, wherein the composite elastic modulus of the resin material constituting the lid material is 2.5 GPa or less as measured by nanoindentation.

[0023] Furthermore, a third embodiment of the method for manufacturing a micro-channel chip according to the present disclosure includes the steps of applying a photosensitive resin onto a substrate, exposing the applied photosensitive resin to light, developing the exposed photosensitive resin and rinsing it with pure water to form a partition layer that defines a channel on the substrate, and bonding a lid material to a surface of the partition layer opposite to the surface that contacts the substrate, and the micro-channel chip after the lid material is bonded to the partition layer has a flatness of 6.5 μm or less in PV value in any 10 mm square area.

[0024] It is sufficient that the lid material satisfies the above condition in only one of the hardness indices (rubber hardness, composite elastic modulus), but it may also satisfy the above condition in both. Furthermore, it is sufficient for the microchannel chip to satisfy either the above-mentioned hardness index (rubber hardness, composite elastic modulus) of the cover material or the flatness (amount of warping) of the microchannel chip, but both may also satisfy the above-mentioned conditions. Although the partition wall layer is made of resin, the present invention is also applicable to the case where the partition wall layer is made of a material other than resin, for example, the present invention is also applicable to the case where the partition wall layer is made of glass, metal, or ceramic.

[0025] The micro-channel chips according to the first to third embodiments and the manufacturing methods of the micro-channel chips according to the first to third embodiments will be described in more detail below. The micro-channel chips according to the first to third embodiments are identical except for the physical properties (rubber hardness, composite elastic modulus) of the resin material constituting the lid material or the flatness of the micro-channel chip, and therefore the micro-channel chips according to the first to third embodiments will be described together. The same applies to the manufacturing methods of the micro-channel chips according to the first to third embodiments. In the following description, the substrate side of the micro-channel chip may be referred to as "bottom", and the side opposite the substrate side of the micro-channel chip (ie, the lid side) as "top".

[0026] (1) Structure of the microfluidic chip 1 and the AA cross-sectional view of Fig. 2, the micro-channel chip according to this embodiment includes a substrate 10, a partition layer 20 provided on the substrate 10, and a lid member 30 provided on the surface of the partition layer 20 opposite to the surface in contact with the substrate 10. The micro-channel chip according to this embodiment also includes an input section 1 for introducing a fluid (e.g., a liquid), a channel 3 through which the fluid introduced from the input section 1 flows, and an output section 2 for discharging the fluid from the channel 3 and air present inside the channel 3.

[0027] The flow channel 3 is an area surrounded by the substrate 10, the partition layer 20, and the lid material 30, and a pattern is defined by the partition layer 20. The input section 1 and the output section 2 are through-holes provided in the lid material 30, and the input section 1 is connected to one end of the flow channel 3, and the output section 2 is connected to the other end. The lid material 30 may be transparent so that the inside of the flow channel 3 can be viewed, or may be opaque.

[0028] In the micro-channel chip according to this embodiment, at least one each of the input section 1 and the output section 2 may be provided, and multiple each may be provided. In addition, in the micro-channel chip according to this embodiment, one or multiple channels 3 may be provided. Furthermore, the channel 3 may have a pattern that allows the fluid introduced from the input section 1 to merge or branch.

[0029] (2) Circuit Board The substrate 10 can be made of a light-transmitting or non-light-transmitting material. For example, when the state (fluid state) inside the flow channel 3 is detected and observed by light, a material having excellent transparency to the light is used. Examples of light-transmitting materials include inorganic materials such as glass, silicon, sapphire (Al2O3), silicon nitride (SiN), and silicon carbide (SiC).

[0030] When it is not necessary to detect or observe the state (fluid state) inside the flow channel 3 by light, a non-light-transmitting material may be used. Examples of non-light-transmitting materials include a silicon wafer and a copper plate. The thickness of the substrate 10 is not particularly limited, but since a certain degree of rigidity is required when manufacturing a micro-channel chip, the thickness is preferably within the range of 10 μm (0.01 mm) to 10 mm.

[0031] (3) Partition layer The partition layer 20 can be made of a resin such as a photosensitive resin. An example of the photosensitive resin is a resin that is photosensitive to light having a wavelength of 190 nm or more and 400 nm or less, which is in the ultraviolet light region. Such a photosensitive resin is a photoresist such as a liquid resist or a dry film resist. The photoresist may be either a positive type in which the photosensitive region dissolves, or a negative type in which the photosensitive region becomes insoluble. An example of a photosensitive resin composition suitable for forming the partition layer 20 is a radical negative type photosensitive resin composition containing an alkali-soluble polymer, an addition polymerizable monomer, and a photopolymerization initiator.

[0032] The basic structure (skeleton) of the photosensitive resin is not particularly limited as long as it has photosensitivity, and examples thereof include acrylic resins, acrylic urethane resins (urethane acrylate resins), epoxy resins, polyamide resins, polyimide resins, polyurethane resins, polyester resins, polyether resins, polyolefin resins, polycarbonate resins, polystyrene resins, norbornene resins, and phenol novolac resins. These may be used alone or in the form of a mixture or copolymer of two or more types.

[0033] In this embodiment, the resin constituting the partition layer 20 is not limited to a photosensitive resin, and may be, for example, a synthetic resin. Examples of the synthetic resin that may be used include polymethylmethacrylate (PMMA), polycarbonate (PC), polystyrene (PS), polypropylene (PP), cycloolefin polymer (COP), and cycloolefin copolymer (COC).

[0034] Further, the thickness of the partition layer 20, i.e., the height of the flow channel 3, is not particularly limited, but the height of the flow channel 3 needs to be greater than the substance to be analyzed or inspected (e.g., medicine, 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 20, i.e., the height of the flow channel 3, is preferably 5 μm or more and 100 μm or less. Similarly, since the width of the flow path 3 needs to be larger than the substance to be analyzed or inspected, the width of the flow path 3 defined by the partition layer 20 is preferably 5 μm or more and 1000 μm or less, and more preferably 5 μm or more and 100 μm or less.

[0035] (4) Lid material In the micro-channel chip according to this embodiment, the lid member 30 covers the channel 3 as shown in Fig. 2. The lid member 30 is provided on the surface of the partition layer 20 opposite to the surface that contacts the substrate 10, and faces the substrate 10 across the partition layer 20. More specifically, as shown in Fig. 2, in a cross-sectional view, the side ends of the lid member 30 are supported by the partition layer 20, and the central region faces the substrate 10, and the central region defines the upper portion of the channel 3.

[0036] The thickness of the lid material 30 is not particularly limited, but considering that through holes corresponding to the input section 1 and the output section 2 are provided in the lid material 30, the thickness is preferably in the range of 10 μm (0.01 mm) to 10 mm, and more preferably in the range of 50 μm to 2 mm. Note that it is preferable to previously form through holes corresponding to the input section 1 and the output section 2 of the fluid in the lid material 30 before bonding with the partition layer 20. This makes it possible to prevent problems with dust and contamination from occurring, compared to the case where through holes are formed after bonding with the partition layer 20.

[0037] The lid member 30 can be made of a light-transmitting or non-light-transmitting material. For example, when the state (fluid state) inside the flow channel 3 is detected and observed by light, a resin material having excellent transparency to the light may be used. When it is not necessary to detect and observe the state (fluid state) inside the flow channel 3 by light, a non-light-transmitting material may be used.

[0038] The lid material 30 satisfies one of the following physical property (hardness index) conditions. That is, the rubber hardness of the lid material 30 measured with a micro rubber hardness meter is 97.5 points or less, or the composite elastic modulus of the resin material of the lid material 30 measured with a nanoindentation method is 2.5 GPa (2500 MPa) or less. The lid material 30 may satisfy either the condition of rubber hardness or the composite elastic modulus, but may also satisfy both physical properties.

[0039] If the lid material 30 satisfies the above physical properties, i.e., the hardness index (rubber hardness, composite modulus of elasticity), the internal stress of the lid material 30 caused by the thermal history during bonding (lamination) of the partition layer 20 and the lid material 30 is suppressed. This reduces the shear stress at the bonding surface between the partition layer 20 and the lid material 30. This makes it possible to suppress the occurrence of peeling between the partition layer 20 (microchannel substrate) and the lid material 30 due to changes over time in a microchannel chip in which a microchannel substrate (substrate 10, partition layer 20) that forms the channel 3 and a lid material are bonded. As will be described in detail later, if the lid material 30 satisfies the above hardness index, peeling is suppressed even after at least one week has passed since the bonding of the lid material 30. In addition, when the micro-channel chip according to this embodiment satisfies the above-mentioned condition for the amount of warping (flatness), it is not essential that the cover material 30 satisfies the above-mentioned conditions for the hardness index (rubber hardness, composite elastic modulus). The details of the amount of warping will be described later.

[0040] Examples of the resin material constituting the lid member 30 include silicone rubber (e.g., polydimethylsiloxane (PDMS)) and synthetic resin. Examples of the synthetic resin include acrylic resin, methacrylic resin (e.g., polymethylmethacrylate (PMMA)), polypropylene (PP), polycarbonate (PC), polystyrene (PS), cycloolefin polymer (COP), cycloolefin copolymer (COC), polyester (e.g., polyethylene terephthalate (PET), polyurethane, polyvinyl chloride, silicone resin, fluororesin, etc.

[0041] Regarding the method of measuring the rubber hardness of the lid material 30, if the thickness of the lid material 30 is less than 6 mm, if a general-purpose rubber hardness tester is used, the hardness information of the material constituting the layer below the lid material 30 (for example, the partition layer 20 and the substrate 10) will also be included. For this reason, the rubber hardness of the lid material 30 cannot be measured accurately. Therefore, if the thickness of the lid material 30 is less than 6 mm, the rubber hardness is measured using the Type A method of a micro rubber hardness tester (for example, MD-1 manufactured by Kobunshi Keiki Co., Ltd.) that can measure thin films up to a thickness of about 1 mm. On the other hand, if the thickness of the lid material 30 is 6 mm or more, the rubber hardness can be measured using a general-purpose rubber hardness tester (durometer). In this case, the maximum reading value of a Type A durometer conforming to JIS K 6253 when pressure is applied for 1 second or more is taken as the value of the rubber hardness of the lid material 30. Details are as described in JIS K 6253, so a description will be omitted.

[0042] The composite elastic modulus of the resin material constituting the lid material 30 is a composite elastic modulus measured at 25°C by a nanoindentation method. The composite elastic modulus measured by the nanoindentation method is a physical property value that indicates the hardness of the elastic deformation components of the material. The specific method for measuring the composite elastic modulus is as described in the international standard ISO14577 by the International Organization for Standardization (ISO), and therefore a detailed description is omitted here.

[0043] (5) Warpage of the microfluidic chip The amount of warping of a microchannel chip is quantified as a PV (peak to valley) value, which is a measurement of flatness. The PV value is the difference between the maximum height and the minimum height measured in a specific area of ​​the microchannel chip. Therefore, the amount of warping (PV value) of the microchannel chip also represents the difference in strain within that area.

[0044] In the micro-channel chip of this embodiment, after the lid material 30 and the partition layer 20 are bonded (more specifically, immediately after bonding), the flatness in any 10 mm square area (a square area with one side measuring 10 mm) is 6.5 μm or less in PV value. As described above, the amount of warping (PV value) of the micro-channel chip represents the magnitude of internal stress that occurs and remains in the lid material 30 due to the thermal history when bonded to the partition layer 20. In this embodiment, if the amount of warping (PV value) of the micro-channel chip is 6.5 μm or less, the internal stress remaining in the lid material 30 is reduced, and peeling between the lid material 30 and the partition layer 20 due to changes over time can be suppressed.

[0045] The amount of warpage (the above PV value) in the microchannel chip can be measured for any region of the substrate 10 or the lid material 30. Specifically, the PV value is measured immediately after the lid material 30 and the partition layer 20 are bonded (laminate) for any region (10 mm square) in either the back surface of the substrate 10 or the front surface (the surface opposite to the substrate 10) of the lid material 30, which are in a flat state before bonding. Of the substrate 10 and the lid member 30, it is preferable to measure the rear surface of the substrate 10 as the object of measurement for the amount of warpage. This is because the lid member 30 is made of a resin material, and the partition layer 20 is more likely to have uneven thickness or waviness than the substrate 10, and thickness unevenness may occur at a stage before bonding with the partition layer 20 (during the process of forming the lid member) depending on the type of resin. The microchannel chip of this embodiment is such that the PV value (warping amount) of flatness measured over a 10 mm square area does not exceed 6.5 μm at any point in the area to be measured (e.g., the back surface of substrate 10), i.e., the maximum PV value within the area is 6.5 μm.

[0046] In the microchannel chip according to this embodiment, the flatness (warpage) is measured using a white light interference microscope, a laser microscope, a laser displacement meter, a stylus-type shape measuring instrument, etc. With these instruments, the difference between the maximum height and the minimum height (PV value) of the region to be measured (the rear surface of the substrate 10 or the front surface of the lid material 30) is measured, and the measured PV value is regarded as the warpage.

[0047] When the amount of warping is measured over the entire surface of the micro-channel chip (e.g., the entire surface of the substrate 10 or the lid 30), the larger the chip size, the larger the value of the warping. Also, when a selected area is measured, the larger the selected area, the larger the value of the warping. Therefore, in order to accurately express the internal stress remaining in the lid 30, i.e., the magnitude of the shear stress occurring at the bonding surface between the lid 30 and the partition layer 20, it is preferable to measure the PV value per unit area. For this reason, as described above, the PV value in an arbitrary 10 mm square (10 mm x 10 mm) area of ​​the micro-channel chip (substrate 10 or lid 30) is measured as the amount of warping, which is an area that can be measured based on the size of a general micro-channel chip.

[0048] In addition, when the microchannel chip of this embodiment satisfies the above-mentioned conditions for the hardness index (rubber hardness, composite elastic modulus) of the lid material 30, it is not essential that the above-mentioned condition for flatness (amount of warping) is also satisfied. However, by satisfying both the conditions for the hardness index and the amount of warping, peeling between the lid material 30 and the partition layer 20 due to changes over time can be more reliably suppressed. In other words, the micro-channel chip according to this embodiment may satisfy both or either of the conditions for the hardness index and the warpage amount for the lid material 30. As described above, the micro-channel chip may satisfy either or both of the conditions for the hardness index of the lid material 30, that is, the rubber hardness and the composite elastic modulus.

[0049] (6) Middle class The micro-channel chip according to this embodiment may include an intermediate layer between the substrate 10 and the partition layer 20. That is, the micro-channel chip in FIGS. 1 and 2 may include a substrate 10, an intermediate layer (not shown) disposed on the substrate 10, the partition layer 20 disposed on the intermediate layer, and a lid material 30 disposed on the partition layer 20.

[0050] Examples of the intermediate layer include an adhesion layer that improves adhesion between the substrate 10 and the partition layer 20, and a light-shielding layer that imparts light-shielding properties to the microchannel chip. When glass is used as the substrate 10, it is preferable to provide an adhesion layer between the substrate 10 and the partition layer 20. Examples of the adhesion layer include a hydrophobic surface treatment layer formed by performing a hydrophobic surface treatment (HMDS treatment) on the surface of the substrate 10, a thin resin film coated on the surface of the substrate 10, and the like.

[0051] When the microchannel chip according to this embodiment has an adhesion layer, the fluid (e.g., liquid) flowing through the channel 3 comes into contact with the adhesion layer rather than the substrate 10. For this reason, it is preferable that the adhesion layer has resistance to the fluid introduced into the channel 3. By providing an adhesion layer on the substrate 10, it is possible to improve the resolution of the channel pattern formed by the photosensitive resin.

[0052] (7) Manufacturing method of microfluidic chip A method for manufacturing a microchannel chip according to this embodiment will be described with reference to Fig. 3. Here, an example will be described in which the partition layer 20 is formed from a photosensitive resin. Each view in Fig. 3 is a cross-sectional view of the substrate 10 cut along a plane parallel to the direction in which the channel 3 extends and perpendicular to the surface of the substrate 10.

[0053] The method for manufacturing the microchannel chip according to this embodiment includes a coating step of coating a photosensitive resin onto a substrate 10, an exposure step of exposing the coated photosensitive resin to light, a development step of developing and washing the exposed photosensitive resin to form a partition layer 20 that defines a channel 3 on the substrate 10, and a bonding step of bonding a lid material 30 to the surface of the partition layer 20 opposite to the surface that contacts the substrate 10.

[0054] <Coating process> First, a coating step is performed to form a photosensitive resin layer 51 on the substrate 10 for forming the partition wall layer 20 on the substrate 10. The method for applying the photosensitive resin onto the substrate 10 is not particularly limited, but examples thereof include spin coating, spray coating, bar coating, etc. Among these methods, spin coating is preferred from the viewpoint of controllability of the film thickness.

[0055] Photosensitive resin in various forms, such as liquid, solid, gel, film, etc., can be applied onto the substrate 10. Among these, it is preferable to form the photosensitive resin layer 51 using a liquid resist. Although the thickness of the photosensitive resin layer 51 is not particularly limited, it is preferable to set the thickness of the photosensitive resin layer 51 and apply the photosensitive resin so that the thickness of the completed partition wall layer 20 is a desired value. When the photosensitive resin contains a solvent, the solvent may be removed from the photosensitive resin layer 51 by a method such as a heat treatment or a reduced pressure treatment.

[0056] <Exposure process> Following the coating step, an exposure step is carried out. That is, a pattern of the flow path 3 is drawn on the photosensitive resin layer 51 on the substrate 10 by exposure. The type of light used for exposure is not particularly limited, and ultraviolet light or a laser can be used. That is, exposure can be carried out by, for example, an exposure device that irradiates ultraviolet light or a laser drawing device.

[0057] Among these, exposure using a proximity exposure device or a contact exposure device that irradiates ultraviolet light is preferred. In the case of a proximity exposure device, exposure is performed through a photomask having a pattern of the flow channel in the micro-channel chip. As this photomask, for example, a photomask having a two-layer structure of chromium and chromium oxide as a light-shielding film may be used.

[0058] When a photosensitive resin that is sensitive to light having a wavelength of 190 nm or more and 400 nm or less, which is in the ultraviolet light region, is used as the photosensitive resin, light having a wavelength of 190 nm or more and 400 nm or less, which is in the ultraviolet light region, is used for exposure to expose the photosensitive resin to the light having a wavelength of 190 nm or more and 400 nm or less.

[0059] When the photosensitive resin applied onto the substrate 10 is a positive resist, the exposed regions dissolve to become the flow paths 3, and the photosensitive resin remaining in the unexposed regions becomes the partition wall layer 20. When the photosensitive resin applied onto the substrate 10 is a negative resist, the photosensitive resin remaining in the exposed regions becomes the partition wall layer 20, and the unexposed regions dissolve to become the flow paths 3. FIG. 3 shows an example in which the photosensitive resin is a negative resist, with reference numeral 52 indicating an exposed region and reference numeral 53 indicating an unexposed region.

[0060] In this manner, in the method for manufacturing the micro-channel chip according to this embodiment, the partition layer 20 that defines the channel 3 can be formed on the substrate 10 by using photolithography. When a chemically amplified resist or the like is used to form the partition layer 20 on the substrate 10, a heat treatment (post-exposure bake: PEB) may be further performed after exposure in order to promote a catalytic reaction of the acid generated by exposure.

[0061] <Developing process> Next, the exposed photosensitive resin is developed to form a pattern of the flow path 3. The development is carried out by reacting the photosensitive resin with a developer in a developing device such as a spray type, a dip type, or a paddle type.

[0062] The developer may be, for example, an aqueous solution of sodium carbonate, an aqueous solution of tetramethylammonium hydroxide, an aqueous solution of potassium hydroxide, or an organic solvent. The developer may be selected appropriately according to the characteristics of the photosensitive resin, and is not limited to the above. The concentration of the developer and the development time may be adjusted to suit the characteristics of the photosensitive resin.

[0063] After the development, cleaning is performed to remove the developer used in the development process from the photosensitive resin layer 51 on the substrate 10. The cleaning method is not particularly limited, and can be performed, for example, by using a cleaning device of a spray type, shower type, immersion type, or the like. As the cleaning liquid, for example, pure water, isopropyl alcohol, or the like can be used, and a cleaning liquid suitable for removing the developer used in the development process may be appropriately selected. After the cleaning, drying may be performed using a spin dryer, an IPA vapor dryer, natural drying, or the like.

[0064] <Surface modification process> After the development step is completed, a surface modification treatment may be performed to modify one or both of the surfaces of the partition layer 20 and the lid material 30 before the bonding step is performed. Examples of the surface modification treatment include plasma treatment, UV (ultraviolet) treatment, corona discharge treatment, and excimer laser treatment. If a functional group such as a hydroxyl group (-OH) is imparted to one or both of the surfaces of the partition layer 20 and the lid material 30 by the surface modification treatment, the strength of the bond between the partition layer 20 and the lid material 30 in the subsequent bonding step can be increased.

[0065] <Joining process> Next, a lid material 30 is bonded to the surface of the partition layer 20 opposite to the surface in contact with the substrate 10. By bonding the lid material 30, the channel 3 is covered with the lid material 30, and the microchannel chip shown in Figs. 1 and 2 is obtained. The lid material 30 to be bonded satisfies at least one of the above conditions in terms of rubber hardness and composite modulus, which are hardness indexes. That is, at least one of the two conditions that the rubber hardness of the lid material 30 is 97.5 points or less, or the composite modulus of the resin material measured by the nanoindentation method is 2.5 GPa or less is satisfied. Furthermore, the micro-channel chip after the lid material 30 and the partition layer 20 are bonded by the bonding step may be configured to satisfy the condition that the flatness in any 10 mm square area is 6.5 μm or less in PV value. As described above, the micro-channel chip only needs to satisfy at least one of the conditions of the hardness index of the lid material 30 and the condition of the warpage amount (PV value). This makes it possible to suppress peeling between the lid material 30 and the partition layer 20 due to changes over time.

[0066] The method for joining the partition layer 20 and the lid material 30 is not particularly limited, and they may be joined using an adhesive, but as long as the physical properties of the lid material 30 satisfy the requirements of this disclosure (the conditions for the above hardness index), they can be joined without using an adhesive. That is, if the physical properties of the lid material 30 satisfy the requirements of the present disclosure (the conditions of the hardness index), the surface of the lid material 30 is flexible, so that when the partition layer 20 and the lid material 30 are bonded together, the surface of the lid material 30 undergoes elastic or plastic deformation in conformity with the fine uneven shape of the surface of the partition layer 20. Therefore, the partition layer 20 and the lid material 30 are firmly adhered to each other, and minute gaps are unlikely to occur at the interface between the partition layer 20 and the lid material 30. For example, thermocompression bonding can be used as a method for bonding the partition layer 20 and the lid material 30. This is a method used for bonding the partition layer 20 and the lid material 30 by heating and pressing them together.

[0067] The temperature conditions for bonding the partition layer 20 and the lid material 30 are not particularly limited, and the bonding may be performed at room temperature or at a temperature higher than room temperature. The temperature conditions may be appropriately set depending on the above-mentioned physical properties of the resin material constituting the lid material 30 and the pressure conditions described below. The temperature conditions are preferably, for example, a temperature that is equal to or higher than room temperature and does not exceed the heat resistance temperature of the resin material, more preferably 40°C or higher and 200°C or lower, and even more preferably 60°C or higher and 100°C or lower. In the present invention, room temperature means 20°C.

[0068] The pressure conditions for bonding the partition layer 20 and the lid material 30 are not particularly limited, and the bonding may be performed without applying pressure to the partition layer 20 and the lid material 30, or may be performed while applying pressure to one or both of the partition layer 20 and the lid material 30. The pressure conditions may be appropriately set depending on the above-mentioned physical properties of the resin material constituting the lid material 30 and the above-mentioned temperature conditions. The pressure conditions are preferably, for example, 0.001 MPa or more and 1 MPa or less, and more preferably 0.001 MPa or more and 0.01 MPa or less. Depending on the above-mentioned physical properties of the resin material constituting the lid material 30 and the above-mentioned temperature conditions, deformation occurs due to its own weight even without applying any pressure, so it is also possible to bond the material without applying any pressure.

[0069] When the resin material constituting the lid member 30 is polydimethylsiloxane, the temperature condition is preferably 100° C. or more and 200° C. or less, and the pressure condition is preferably 0.001 MPa or more and 0.01 MPa or less. When the resin material is silicone rubber, the temperature condition is preferably 100° C. or higher and 200° C. or lower, and the pressure condition is preferably 0.001 MPa or higher and 0.01 MPa or lower.

[0070] When the resin material is polyurethane, the temperature condition is preferably 60° C. or more and 100° C. or less, and the pressure condition is preferably 0.005 MPa or more and 0.05 MPa or less. When the resin material is polyvinyl chloride, the temperature condition is preferably 20° C. or more and 60° C. or less, and the pressure condition is preferably 0.005 MPa or more and 0.05 MPa or less. When the resin material is polyethylene terephthalate, polycarbonate, polymethyl methacrylate, or cycloolefin polymer, the temperature condition is preferably 40° C. or more and 90° C. or less, and the pressure condition is preferably 0.01 MPa or more and 1 MPa or less.

[0071] A specific method for bonding the partition layer 20 and the lid material 30 includes, for example, thermocompression bonding using a heat press machine or a heat roll machine. The partition layer 20 and the lid material 30 may be bonded to each other by a surface modification treatment. Examples of the surface modification treatment include UV treatment, plasma treatment, corona discharge treatment, excimer laser treatment, and surface modification using a silane coupling agent. The surface modification treatment may be performed on the respective bonding surfaces of the partition layer 20 and the lid material 30. In this case, an appropriate optimal treatment method may be selected according to the affinity and adhesive compatibility between the partition layer 20 and the lid material 30. The partition layer 20 and the lid material 30 may be bonded to each other by performing a heat treatment after performing a surface modification treatment on the respective bonding surfaces of the partition layer 20 and the lid material 30. The bonding method is not limited to thermocompression bonding and surface modification treatment, and the partition layer 20 and the lid material 30 may be bonded using an adhesive (e.g., a pressure sensitive adhesive, a sealant, a double-sided tape, an adhesive tape, etc., having a thickness of several μm to several tens of μm). The type of adhesive to be used can be determined based on the affinity between the materials constituting the partition layer 20 and the lid material 30. For example, an acrylic resin adhesive, a urethane resin adhesive, an epoxy resin adhesive, etc. can be used.

[0072] (Effects of this embodiment) The micro-channel chips according to the first to third embodiments can provide the following effects. (1) The microchannel chip of the first embodiment comprises a substrate 10, a partition layer 20 provided on the substrate 10 to define a channel, and a lid material 30 provided on the side of the partition layer 20 opposite to the side in contact with the substrate 10, and the rubber hardness of the lid material 30 measured with a micro rubber hardness tester is 97.5 points or less. This configuration suppresses internal stress in the lid material 30 that occurs due to thermal history during bonding (lamination) of the partition layer 20 and the lid material 30, and reduces shear stress at the bonding surface between the partition layer 20 and the lid material 30. Therefore, in a micro-channel chip in which a micro-channel base material (substrate 10, partition layer 20) that forms the channel 3 and a lid material are bonded, peeling between the partition layer 20 and the lid material 3 due to changes over time can be suppressed. (2) The microchannel chip of the second embodiment comprises a substrate 10, a partition layer 20 provided on the substrate 10 to define a channel, and a lid material 30 provided on the side of the partition layer 20 opposite to the side in contact with the substrate 10, the lid material 30 being made of a resin material having a composite elastic modulus of 2.5 GPa or less as measured by nanoindentation. Even in this configuration, in a micro-channel chip in which a micro-channel substrate forming channel 3 and a lid material are joined, peeling between partition layer 20 and lid material 30 due to changes over time can be suppressed. (3) The micro-channel chip of the third embodiment comprises a substrate 10, a partition layer 20 provided on the substrate 10 to define a channel, and a lid material 30 provided on the side of the partition layer 20 opposite the side that contacts the substrate 10, and the flatness of any 10 mm square area in the micro-channel chip after bonding the lid material 30 and the partition layer 20 is 6.5 μm or less in PV value. Even in this configuration, the internal stress remaining in the lid material 30 when it is bonded to the partition layer 20 is reduced, making it possible to suppress peeling between the lid material 30 and the partition layer 20 due to changes over time.

[0073] (4) In the micro-channel chip of (3) above, cover member 30 may be made of a resin material, and the resin material may have a composite elastic modulus of 2.5 GPa or less as measured by nanoindentation. According to this configuration, the internal stress remaining in the lid material 30 is reliably reduced, and peeling between the lid material 30 and the partition layer 20 due to changes over time can be more reliably suppressed. (5) In any one of the micro-channel chips (2) to (4) above, the rubber hardness of the cover material 30 measured with a micro rubber hardness meter may be 97.5 points or less. According to this configuration, the internal stress remaining in the lid material 30 is reliably reduced, and peeling between the lid material 30 and the partition layer 20 due to changes over time can be more reliably suppressed.

[0074] (6) In the micro-channel chips of (1) to (3) above, the substrate 10 may contain at least one of glass, silicon, sapphire (Al2O3), silicon nitride (SiN), and silicon carbide (SiC). According to this configuration, the state inside the flow channel 3 (the state of the fluid) can be detected and observed by light. (7) In the microchannel chips of (1) to (3) above, the resin material constituting the cover material 30 may contain at least one of polydimethylsiloxane, silicone rubber, polyurethane, polyvinyl chloride, acrylic resin, polypropylene, polycarbonate, polystyrene, cycloolefin polymer, cycloolefin copolymer, and polyethylene terephthalate. According to this configuration, the hardness index (rubber hardness, composite elastic modulus) of the lid material 30 can be suitably controlled. (8) In the micro-channel chips of (1) to (3) above, the partition layer 20 may be made of a photosensitive resin that is sensitive to light having a wavelength of 190 nm or more and 400 nm or less, which is in the ultraviolet light region. According to this configuration, the partition layer 20 can be suitably formed on the substrate 10 by photolithography. EXAMPLES

[0075] The present invention will be specifically described below with reference to examples, but the present invention is not limited to the following examples. Microchannel chips of Examples 1 to 14 and Comparative Examples 1 to 6 were manufactured according to the procedures described below.

[0076] <Formation of partition layer> First, a transparent photosensitive resin was applied to a square glass substrate with sides of 10 cm to form a photosensitive resin layer. A negative photosensitive resin (model number KMPR1035, manufactured by Nippon Kayaku Co., Ltd.) with an epoxy resin skeleton was used as the photosensitive resin. The photosensitive resin was applied to the glass substrate using a spin coater. The rotation speed and application time were adjusted so that the photosensitive resin layer had a film thickness of 50 μm, with a rotation speed of 1700 rpm and application time of 30 seconds.

[0077] Next, in order to remove the solvent contained in the photosensitive resin layer, a heat treatment (pre-baking) was performed using a hot plate at a temperature of 90° C. for 20 minutes. Next, the photosensitive resin layer on the glass substrate was exposed to light to draw a flow path pattern. Specifically, the photosensitive resin layer was exposed to a pattern through a photomask having a pattern arrangement of microflow paths. The photomask used had a light-shielding film having a two-layer structure of chromium and chromium oxide. A proximity exposure device was used for exposure. The exposure device used a high-pressure mercury lamp as the light source, and the exposure wavelength was broadband including g-rays, h-rays, and i-rays. The exposure dose for forming the flow path pattern was 500 mJ / cm. 2 It was decided.

[0078] Next, the exposed photosensitive resin layer was subjected to a heating treatment (post-exposure bake: PEB) using a hot plate at 100°C for 240 seconds, followed by development to form a flow path pattern. The development conditions were as follows: the photosensitive resin layer was developed for 360 seconds using an alkaline developer (aqueous solution containing 2.38% by mass of tetramethylammonium hydroxide), dissolving the unexposed parts and patterning the flow path structure. Subsequently, shower rinsing with ultrapure water was performed to remove the developer from the photosensitive resin layer on the substrate, and drying was performed with a spin dryer to form a partition layer. The line width of the opening of the flow channel in the partition layer fabricated by the above steps was set to 100 μm, which is typical for microflow channels such as drug-resistant bacteria test chips.

[0079] <Cutting> The glass substrate on which the barrier rib layer was formed was cut to a size suitable for observation under a microscope (length: 25 mm, width: 75 mm), and then washed with a shower of pure water and dried with an air blower.

[0080] <Preparing the lid material> Films with a thickness of 1.5 mm made of silicone rubber, polyurethane, polyvinyl chloride, polymethyl methacrylate (PMMA), polyethylene terephthalate (PET), polycarbonate (PC), or cycloolefin polymer (COP) were prepared. These films were then cut into pieces measuring 25 mm in length and 75 mm in width to create lids. Furthermore, the lids were punched or cut to open through holes with a diameter of 1 mm that correspond to the input and output sections.

[0081] The silicone rubber is an ultra-transparent silicone rubber sheet, GSSC series, manufactured by Tomita Matex Co., Ltd. The polyurethane is a urethane resin, BM series, manufactured by ADEKA Corporation. The polyvinyl chloride is a vinyl chloride resin, TK series, manufactured by Shin-Etsu Chemical Co., Ltd. The polymethyl methacrylate is a methacrylic resin sheet, COMOGLAS (registered trademark), manufactured by Kuraray Co., Ltd. The polyethylene terephthalate is a polyethylene terephthalate, CLAPET (registered trademark), manufactured by Kuraray Co., Ltd. The polycarbonate is a polycarbonate resin, PANLITE (registered trademark), manufactured by Teijin Limited. The cycloolefin polymer is a cycloolefin polymer, ZEONOR (registered trademark), manufactured by Zeon Corporation.

[0082] <Evaluation of the physical properties of resin materials> The physical properties of the resin material that constitutes the lid, i.e., the composite elastic modulus, were measured by the nanoindentation method. The nanoindentation method is a measurement method in which a quasi-static indentation test is performed on the target object to obtain the mechanical properties of the object. The film used to create the lid was cut to prepare a square test piece with a side length of 2 cm, which was then attached to the sample stage of the measurement device using instant adhesive (Aron Alpha (product name) manufactured by Toa Gosei Co., Ltd.).

[0083] The composite elastic modulus and hardness were measured using a nanoindenter Hysitron TI-Premier (product name) manufactured by Bruker Japan Co., Ltd. The indenter used for pressing was a Berkovich type diamond indenter manufactured by Bruker Japan Co., Ltd. The nanoindentation measurement was performed as follows. That is, in the displacement control mode, the indenter was pressed to a depth of 500 nm at a pressing speed of 100 nm / sec, and after holding at the maximum depth for 5 seconds, the load was removed at a speed of 100 nm / sec. This operation was performed at 30 measurement points on the surface of the test piece. The intervals between each measurement point were set to be 100 μm or more.

[0084] The composite elastic modulus was calculated from the data obtained by the above measurements. That is, the unloading curve in the 60-95% range of the maximum load at the time of unloading was analyzed by the Oliver-Pharr method, and the composite elastic modulus was calculated. The results are shown in Table 1. The same measurements were also performed on fused quartz, which serves as a standard sample, to obtain the relationship between the contact depth and contact projected area between the indenter and the test piece, and the measurement data of the test piece was calibrated using this data.

[0085] <Evaluation of physical properties of lid materials> Next, the rubber hardness of the lid material was measured using the Type A method of a micro rubber hardness tester (MD-1, manufactured by Kobunshi Keiki Co., Ltd.). The shape of the indenter was Type A (cylindrical, diameter 0.16 mm, height 0.5 mm), and the maximum spring load of the indenter (load at rubber hardness 100 points) was 332 mN (33.85 g weight). The indenter was pressed to the pressing position at a pressing speed of 5 mm / sec, and the peak hold (maximum reading) was measured when the indenter was held for 3 seconds.

[0086] <Joining of lid material> A microchannel chip was fabricated by bonding a cover material to the cut glass substrate on which the partition layer was formed. At that time, the bonding surfaces of the partition layer and the cover material were subjected to a surface modification treatment by UV treatment (10000 mJ / cm 2 ), the two bonding surfaces were brought into contact with each other and heated using a hot plate to bond them.

[0087] In addition, when the lid material was made of silicone rubber, polyurethane, or polyvinyl chloride, the bonding was performed by carrying out a heat treatment while a metal plate with a mass of 800 g (equivalent pressure 0.00418 MPa) was placed on the lid material as a weight to prevent misalignment of the two bonding surfaces.

[0088] In addition, when the lid material was composed of polyethylene terephthalate, polycarbonate, polymethyl methacrylate, and cycloolefin polymer, the materials were bonded using a heat press device while applying a load of 500 kg (equivalent pressure of 2.61 MPa) so that the two bonding surfaces were in contact over their entire surfaces.

[0089] The heat treatment temperature was set to a temperature not exceeding the heat resistance temperature of each resin material. Specifically, when the resin material was silicone rubber, the heat treatment conditions were 200°C for 10 minutes, 100°C for polyurethane, 60°C for polyvinyl chloride, and 60°C for polyethylene terephthalate, polycarbonate, polymethyl methacrylate, and cycloolefin polymer.

[0090] <Evaluation of warpage of microfluidic chips> Next, immediately after bonding the lid material, the back surface of the glass substrate (the surface opposite to the side to which the lid material was bonded) was measured using a white light interference microscope (Zygo, Nexview NX2) to evaluate the amount of warping of the fabricated microchannel chip. The measurement area was a 10 mm square (a square area with one side of 10 mm) near the center of the microchannel chip, and the PV value (Peak to Valley), which is the difference between the maximum height and the minimum height of the measurement area, was used as the measured value of flatness (μm) to quantify the amount of warping. In Table 1, the amount of warping is described as "amount of warping (flatness PV value) of the channel chip (after bonding of the lid material)".

[0091] <Covering material peeling evaluation test> For the micro-channel chips of Examples 1 to 14 and Comparative Examples 1 to 6 produced as described above, a test for evaluating peeling of the lid material from the partition layer (inspection of the presence or absence of peeling of the lid material) was carried out. This test was carried out by visually and microscopically observing the bonding surface between the partition layer and the lid material. The inspection was carried out 3 days, 1 week, 2 weeks, and 4 weeks after bonding (lamination) of the partition layer and the lid material. To eliminate the influence of outside temperature, etc., the samples after lamination were stored in a clean room environment with a room temperature of 23°C and a humidity of 45%. The rubber hardness and composite modulus of the lid material measured for the samples of each Example and Comparative Example, the amount of warping of the microchannel chip (measured flatness (PV value)), and the results of the peeling test are shown in Table 1. In Table 1, peeling (including partial peeling) is indicated as "X", and no peeling is indicated as "O".

[0092] [Table 1]

[0093] As can be seen from Table 1, in all of the samples of the examples and comparative examples, the lid material and the microchannel substrate (partition layer) were in a bonded (bonded) state immediately after bonding, and no peeling occurred, but peeling occurred over time in the samples of comparative examples 1 to 6. Specifically, the samples of comparative examples 1 to 6 did not satisfy either the conditions for the hardness index of the lid material or the conditions for the amount of warping (PV value of flatness) of the microchannel chip, and peeling occurred in at least a part of the bonding surface between the partition layer and the lid material as early as three days after bonding (comparative examples 4 to 6) and as late as one week after bonding (comparative examples 1 to 3). In contrast, the samples of Examples 1 to 12 satisfy the conditions for the hardness index of the lid material (rubber hardness 97.5 points or less, composite elastic modulus 2.5 GPa (2500 MPa) or less) and the conditions for the warpage of the microchannel chip (PV value of flatness 6.5 μm or less). Therefore, even after 4 weeks have passed since lamination, in the samples of Examples 1 to 12, no peeling occurs at the joint surface between the partition layer and the lid material, and it was found that the bond was maintained. Similarly, in the samples of Examples 13 and 14, i.e., samples that satisfy one of the conditions for the hardness index of the lid material, no peeling occurs at the joint surface between the partition layer and the lid material even after 4 weeks have passed since lamination.

[0094] Moreover, for example, this embodiment can have the following configuration. (1) A substrate; A partition layer provided on the substrate and defining a flow path; a cover material provided on a surface of the partition layer opposite to a surface in contact with the substrate, The rubber hardness of the lid material measured with a micro rubber hardness meter is 97.5 points or less. Microfluidic chip. (2) A substrate; A partition layer provided on the substrate and defining a flow path; a cover material provided on a surface of the partition layer opposite to a surface in contact with the substrate, The cover material is made of a resin material, and the composite elastic modulus of the resin material measured by a nanoindentation method is 2.5 GPa or less. Microfluidic chip. (3) A microchannel chip A substrate; A partition layer provided on the substrate and defining a flow path; a cover material provided on a surface of the partition layer opposite to a surface in contact with the substrate, In the micro-channel chip after bonding the lid material and the partition layer, the flatness in any 10 mm square area is 6.5 μm or less in PV value. Microfluidic chip. (4) The lid material is made of a resin material, and the composite elastic modulus of the resin material measured by a nanoindentation method is 2.5 GPa or less. The microchannel chip according to (3) above. (5) The rubber hardness of the lid material measured with a micro rubber hardness meter is 97.5 points or less. The microchannel chip according to any one of (2) to (4) above.

[0095] (6) The substrate contains at least one of glass, silicon, sapphire (Al2O3), silicon nitride (SiN) and silicon carbide (SiC). The microchannel chip according to any one of (1) to (5) above. (7) The resin material constituting the lid material contains at least one of polydimethylsiloxane, silicone rubber, polyurethane, polyvinyl chloride, acrylic resin, polypropylene, polycarbonate, polystyrene, cycloolefin polymer, cycloolefin copolymer, and polyethylene terephthalate. The microchannel chip according to any one of (1) to (6) above. (8) The partition layer is made of a photosensitive resin having sensitivity to light having a wavelength of 190 nm or more and 400 nm or less, which is an ultraviolet light region. The microchannel chip according to any one of (1) to (7) above.

[0096] (9) A step of applying a photosensitive resin onto a substrate; exposing the coated photosensitive resin to light; developing the exposed photosensitive resin and rinsing it with pure water to form a partition layer that defines a flow path on the substrate; and bonding a lid material to a surface of the partition layer opposite to a surface in contact with the substrate, The method for producing a micro-channel chip, wherein the cover material has a rubber hardness of 97.5 points or less as measured by a micro rubber hardness tester. (10) A step of applying a photosensitive resin onto a substrate; exposing the coated photosensitive resin to light; developing the exposed photosensitive resin and rinsing it with pure water to form a partition layer that defines a flow path on the substrate; and bonding a lid member made of a resin material to a surface of the partition layer opposite to a surface in contact with the substrate, The composite elastic modulus of the resin material constituting the lid material is 2.5 GPa or less as measured by a nanoindentation method. A method for manufacturing a microchannel chip. (11) A method for producing a microchannel chip, comprising the steps of: A step of applying a photosensitive resin onto a substrate; exposing the coated photosensitive resin to light; developing the exposed photosensitive resin and rinsing it with pure water to form a partition layer that defines a flow path on the substrate; and bonding a lid material to a surface of the partition layer opposite to a surface in contact with the substrate, In the micro-channel chip after the lid material is bonded to the partition layer, the flatness in any 10 mm square area is 6.5 μm or less in terms of PV value. A method for manufacturing a microchannel chip. (12) The method for producing a micro-channel chip according to (11) above, wherein the cover material is made of a resin material, and the resin material has a composite elastic modulus of 2.5 GPa or less as measured by a nanoindentation method. (13) The rubber hardness of the lid material measured with a micro rubber hardness meter is 97.5 points or less. A method for producing a microchannel chip according to any one of (10) to (12) above. (14) In the step of exposing the photosensitive resin, the photosensitive resin is exposed to light having a wavelength of 190 nm or more and 400 nm or less, which is in the ultraviolet light region. A method for producing a microchannel chip according to any one of (9) to (13) above. (15) In the step of joining the lid material, no adhesive is used. A method for producing a microchannel chip according to any one of (9) to (14) above. (16) In the step of bonding the lid material, the lid material and the partition wall layer are bonded to each other by surface modification or thermocompression bonding. A method for producing the microchannel chip according to (15) above. [Explanation of symbols]

[0097] 1. Input section 2. Output section 3. Flow Path 10... Substrate 20...Partition layer 30...Lid material 41...protrusion 51...Photosensitive resin layer 52 Exposure area 53 Unexposed area

Claims

1. A substrate; A partition layer provided on the substrate and defining a flow path; a cover material provided on a surface of the partition layer opposite to a surface in contact with the substrate, The rubber hardness of the lid material measured by a micro rubber hardness meter is 97.5 points or less. Microfluidic chip.

2. A substrate; A partition layer provided on the substrate and defining a flow path; a cover material provided on a surface of the partition layer opposite to a surface in contact with the substrate, The lid material is made of a resin material, and the composite elastic modulus of the resin material measured by a nanoindentation method is 2.5 GPa or less. Microfluidic chip.

3. A microchannel chip A substrate; A partition layer provided on the substrate and defining a flow path; a cover material provided on a surface of the partition layer opposite to a surface in contact with the substrate, In the micro-channel chip after bonding the lid material and the partition layer, the flatness in any 10 mm square area is 6.5 μm or less in PV value. Microfluidic chip.

4. The lid material is made of a resin material, and the composite elastic modulus of the resin material measured by a nanoindentation method is 2.5 GPa or less. The microchannel chip according to claim 3 .

5. The rubber hardness of the lid material measured by a micro rubber hardness meter is 97.5 points or less. The microchannel chip according to claim 2 .

6. The substrate contains at least one of glass, silicon, sapphire (Al2O3), silicon nitride (SiN) and silicon carbide (SiC). The microchannel chip according to claim 1 .

7. The resin material constituting the lid material contains at least one of polydimethylsiloxane, silicone rubber, polyurethane, polyvinyl chloride, acrylic resin, polypropylene, polycarbonate, polystyrene, cycloolefin polymer, cycloolefin copolymer, and polyethylene terephthalate. The microchannel chip according to claim 1 .

8. The partition layer is made of a photosensitive resin having photosensitivity to light having a wavelength of 190 nm or more and 400 nm or less, which is an ultraviolet light region. The microchannel chip according to claim 1 .

9. A step of applying a photosensitive resin onto a substrate; exposing the coated photosensitive resin to light; developing the exposed photosensitive resin and rinsing it with pure water to form a partition layer that defines a flow path on the substrate; and bonding a lid material to a surface of the partition layer opposite to a surface in contact with the substrate, The method for producing a microchannel chip, wherein the cover material has a rubber hardness of 97.5 points or less as measured by a micro rubber hardness tester.

10. A step of applying a photosensitive resin onto a substrate; exposing the coated photosensitive resin to light; developing the exposed photosensitive resin and rinsing it with pure water to form a partition layer that defines a flow path on the substrate; and bonding a lid member made of a resin material to a surface of the partition layer opposite to a surface in contact with the substrate, The composite elastic modulus of the resin material constituting the lid material is 2.5 GPa or less as measured by a nanoindentation method. A method for manufacturing a microchannel chip.

11. A method for producing a microchannel chip, comprising the steps of: A step of applying a photosensitive resin onto a substrate; exposing the coated photosensitive resin to light; developing the exposed photosensitive resin and rinsing it with pure water to form a partition layer that defines a flow path on the substrate; and bonding a lid material to a surface of the partition layer opposite to a surface in contact with the substrate, In the micro-channel chip after bonding the lid material to the partition layer, the flatness in any 10 mm square area is 6.5 μm or less in PV value. A method for manufacturing a microchannel chip.

12. The method for manufacturing a micro-channel chip according to claim 11 , wherein the cover material is made of a resin material, and the resin material has a composite elastic modulus of 2.5 GPa or less as measured by a nanoindentation method.

13. The rubber hardness of the lid material measured by a micro rubber hardness meter is 97.5 points or less. The method for producing the microchannel chip according to claim 10 .

14. In the step of exposing the photosensitive resin, the photosensitive resin is exposed to light having a wavelength of 190 nm or more and 400 nm or less, which is in the ultraviolet light region. The method for producing the microchannel chip according to claim 9 .

15. In the step of joining the lid material, no adhesive is used. The method for producing the microchannel chip according to claim 9 .

16. In the step of bonding the lid material, the lid material and the partition wall layer are bonded to each other by surface modification or thermocompression bonding. The method for producing a microchannel chip according to claim 15 .

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