Microfluidic chip and method for manufacturing the same
A microfluidic chip with a photosensitive resin partition wall and adhesive-free bonding method enhances solvent resistance, ensuring smooth delivery of organic solvent-based samples by preventing channel narrowing and accumulation.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- TOPPAN HOLDINGS INC
- Filing Date
- 2024-12-12
- Publication Date
- 2026-06-24
AI Technical Summary
Existing microfluidic chips are not resistant to organic solvents, leading to swelling and blockage of channels, which hinders the delivery of organic solvent-based samples.
The microfluidic chip is fabricated using a substrate, partition wall, and lid portion without an adhesive layer, where the partition wall is made of a photosensitive resin with low swelling properties, and the components are bonded through hydrophilic treatment and heat pressing.
The chip exhibits improved resistance to organic solvents, allowing smooth delivery of organic solvent-based samples, including phase-separated liquids and particulate liquids, by preventing channel narrowing and accumulation.
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Figure 2026103103000001_ABST
Abstract
Description
[Technical Field]
[0001] This invention relates to a microfluidic chip and a method for manufacturing the same. [Background technology]
[0002] Conventionally, technologies have been proposed that use photolithography-based process technologies and thick-film process technologies to create minute reaction fields, enabling testing of samples ranging from a few μL to a few nL. Such technologies utilizing minute reaction fields are called μ-TAS (Micro Total Analysis System) (also sometimes referred to as Lab-on-a-Chip or microchemical chip). μ-TAS is applied in areas such as genetic testing, chromosome testing, cell testing, and pharmaceutical development, as well as biotechnology, testing of trace substances in the environment, investigation of the breeding environment of crops, and genetic testing of crops. For example, μ-TAS technology is attracting attention as a technology for easily and quickly performing point-of-care testing (POCT) at the site of sample generation. In particular, in POCT, the samples targeted for analysis are mainly animal bodily fluids, such as blood, saliva, and urine. These bodily fluids contain microparticles of biological origin, such as proteins and cells, and biological information can be obtained by detecting these microparticles with optical or electrical sensors. By introducing μ-TAS into such inspection technologies, significant benefits have been achieved, including automation, increased speed, higher accuracy, lower costs, faster turnaround times, and reduced environmental impact.
[0003] In μ-TAS, micrometer-sized channels (microfluidic channels, microchannels) formed on a substrate are often used, and such substrates are called microfluidic chips (also known as chips or microchips). Microfluidic chips are fabricated by joining multiple components, such as glass, plastic, resin, or metal. As a joining method, a method is often employed in which an intermediate material other than these components is interposed to join the components. Here, so-called adhesives are used as the intermediate material. To explain one example of fabrication, after forming channels on the surface of the components (for example, the surface of the substrate), adhesive is applied to the surface of the wall portion to prevent the fluid from diverting from the channel and placed around the channel. Next, a component that will serve as a lid for the channel is attached to the wall portion to join the components together and form the channel, thus fabricating a microfluidic chip.
[0004] Other methods for joining components together include, for example, the techniques disclosed in Patent Documents 1 to 3. Patent Document 1 aims to "provide a plastic microchip that is bonded relatively low, inexpensively, simply, and securely, and also provides a process for doing so, and further provides a plastic biochip or microanalysis chip utilizing the same," and discloses the following inventions for a plastic microchip, a method for bonding the same, and a biochip or microanalysis chip utilizing the same: "A plastic microchip comprising a plastic substrate having microchannels on its surface and a plastic film, bonded together via an adhesive on the side having microchannels, wherein the adhesive is an ultraviolet-curing adhesive and the thickness of the plastic film is 10 to 300 μm." Furthermore, Patent Document 2 aims to "manufacture a flow channel device that has excellent adhesion between a substrate having a flow channel and a coating material integrated therewith, and that can be used well without any particular inconveniences," and discloses the following as an invention for a method of manufacturing a flow channel device: "A method for manufacturing a flow channel device comprising a substrate having a flow channel and a coating material integrated with the substrate so as to cover the flow channel includes a hydrophilization step of applying a hydrophilic treatment to the substrate, an integration step of overlapping and integrating the hydrophilized substrate and the coating material to obtain a laminate (10) of the substrate and the coating material, and a post-treatment step of holding the laminate (10) in a humid environment at a temperature of 40°C or higher." Furthermore, Patent Document 3 aims to "provide a microfluidic chip that can prevent the elution of adhesive components into the flow channel and suppress the inhibition of the reaction of the solution in the flow channel, and a method for manufacturing the same," and discloses the following as an invention of a microfluidic chip and a method for manufacturing a microfluidic chip: "The microfluidic chip 1 comprises a substrate 10, a partition layer 11 that forms a flow channel portion 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 lid for the flow channel portion 3, and no adhesive layer is provided between the partition layer 11 and the upper cover layer 12." [Prior art documents] [Patent Documents]
[0005] [Patent Document 1] Japanese Patent Publication No. 2007-240461 [Patent Document 2] Japanese Patent Publication No. 2022-077276 [Patent Document 3] Japanese Patent Publication No. 2023-018439 [Overview of the project] [Problems that the invention aims to solve]
[0006] In recent years, applications for microfluidics have expanded to include fields such as environmental substance analysis and microfluidic science plants, where organic solvent-based samples are to be passed through. Consequently, there is a growing demand for microfluidic chips that are compatible with organic solvent-based samples.
[0007] Patent Document 1 describes a method for fabricating a microfluidic chip using an adhesive. The adhesive is composed of a plastic resin, and when a liquid such as an organic solvent passes through it, swelling of the adhesive portion may occur, potentially causing narrowing or blockage of the channel. In addition, the resin of the adhesive may decompose, and the decomposed components may flow into the liquid, potentially hindering the observation of the components that are intended to be observed. Patent Document 1 does not describe the resistance of the microfluidic chip to organic solvents (hereinafter also simply referred to as "organic solvent resistance").
[0008] Patent Document 2 describes a method of joining without using adhesive. According to the method described in Patent Document 2, organic matter and other substances at the interface are removed by UV exposure, exposing the hydroxyl groups of the substrates, which are then bonded together using heat and pressure. This is a technique called hydrophilic bonding, which promotes the diffusion of hydrogen in the hydroxyl groups and promotes the chemical bonding of Si-O-Si. It should be noted that using an ultraviolet-curing adhesive as described in Patent Document 1 is also a type of hydrophilic bonding technique.
[0009] However, Patent Document 2 merely proposes a method for joining materials constituting the flow channel without adhesive, and does not focus on the resistance of organic solvents to the sample / liquid passing through the microchannel. Furthermore, from the viewpoint of improving shape accuracy and moldability, the substrate in Patent Document 2 preferably contains one or more resins selected from the group consisting of (meth)acrylic resins, styrene resins, polycarbonate resins, and polyolefin resins. Microchannels constructed from such materials that do not take organic solvent resistance into consideration will experience narrowing and blockage of the flow channel due to material swelling, hindering liquid flow.
[0010] Patent document 3 also does not describe resistance to organic solvents.
[0011] Therefore, the present invention has been made in view of the above problems, and aims to provide a technology that can improve the organic solvent resistance of microfluidic chips.
Means for Solving the Problem
[0012] To solve the above problems, one of the typical microchannel chips of the present invention includes a substrate portion, a partition portion that forms a flow path on the substrate portion, and a lid portion that is disposed on a portion of the partition portion opposite to the portion where the substrate portion contacts and covers the flow path. The partition portion is formed of a photosensitive resin having radical crosslinkability.
Advantages of the Invention
[0013] According to the present invention, the organic solvent resistance of the microchannel chip can be improved. Problems, configurations, and effects other than those described above will be clarified by the description in the following embodiments for carrying out the invention.
Brief Description of the Drawings
[0014] [Figure 1] FIG. 1 is a diagram showing an example of a prototype (test product) of the microchannel chip of the present disclosure. [Figure 2] FIG. 2 is a diagram schematically showing the shape of a portion having an R shape in the path of the microchannel. [Figure 3] FIG. 3 is a diagram showing an example of the configuration of the microchannel chip of the present disclosure. [Figure 4] FIG. 4 is a flowchart diagram showing an example of a method for manufacturing a microchannel chip. [Figure 5] FIG. 5 is a diagram showing an example of the configuration of the microchannel chip. [Figure 6] FIG. 6 is a diagram showing the configuration of the microchannel chip of Example 1. [Figure 7] FIG. 7 is a diagram showing the configuration of the microchannel chip of Example 2. [Figure 8] FIG. 8 is a flowchart diagram showing an example of a method for manufacturing a laminate of a glass substrate and a lid portion. [Figure 9] FIG. 9 is a diagram showing the configuration of the microchannel chip of Example 3. [Figure 10] Figure 10 shows the configuration of the microfluidic chip in Example 4. [Figure 11] Figure 11 shows the configuration of the microfluidic chip in Example 5. [Figure 12] Figure 12 is a flowchart illustrating an example of a method for fabricating a laminate of a glass substrate and the substrate portion. [Figure 13] Figure 13 is a flowchart illustrating an example of a method for forming a partition wall on a glass substrate. [Modes for carrying out the invention]
[0015] Embodiments of the present invention will be described below with reference to the drawings. However, the present invention is not limited to these embodiments. Furthermore, in the drawings, identical parts are denoted by the same reference numerals. The positions, sizes, shapes, and ranges of the components shown in the drawings may not represent their actual positions, sizes, shapes, and ranges in order to facilitate understanding of the invention. Therefore, the present invention is not necessarily limited to the positions, sizes, shapes, and ranges disclosed in the drawings. Furthermore, when specifying a numerical range, for example, the range of 100 μm to 200 μm may be written as "100~200 μm". The same applies to units other than μm. Furthermore, in this disclosure, "hydrocarbon compounds" refers to compounds composed of carbon and hydrogen. "Alcohol compounds" refers to compounds composed of a hydrocarbon group and a hydroxyl group. "Ketone compounds" refers to compounds having a carbonyl group.
[0016] (Summary of the present invention) Figure 1 shows an example of a prototype of the microfluidic chip according to this disclosure. According to one aspect of the present invention, it is possible to provide a microfluidic chip with excellent resistance to organic solvents and a method for manufacturing the same. The configuration and manufacturing method of the microfluidic chip will be described later.
[0017] Furthermore, according to another aspect of the present invention, by employing a material with a swelling degree of 10% or less in relation to organic solvents in the partition wall, organic solvent-based samples can be smoothly passed through the microchannel. This effect is particularly noticeable when passing through phase-separated liquids (immiscible liquids) or particulate liquids that tend to accumulate in the channel.
[0018] The inventors believe the following reasons exist for this: When delivering liquid into the microchannels of a microfluidic chip, the delivered sample passes through a delivery space formed by the substrate, both partitions, and the lid material. By using a low-swelling material for the partitions, it is possible to prevent narrowing of the delivery space due to swelling on two of the four surfaces in two directions. This prevents the accumulation of phase-separated liquids and particles in those two directions, thus maintaining smooth liquid delivery.
[0019] Figure 2 schematically shows the shape of the R-shaped portion of a microchannel. Generally, microchannels are formed on a two-dimensional plane, and sometimes complex shapes such as zigzag paths are formed within the microchannel. Zigzag paths are necessary when performing reactions or separations of samples within the channel. As shown in Figure 2(a), in channel 100, the liquid is delivered in the direction indicated by the arrow on a two-dimensional plane (XY plane). Of channel 100, the zigzag path portion 110 is usually formed as an R-shape. Figure 2(b)(1) shows channel 100 separated into the zigzag path portion 110 and the other portion, and Figure 2(b)(2) shows a comparison of the areas when the length in the X-axis direction is made common for the zigzag path portion 110 and the other portion. The area of the zigzag path portion 110 is defined as the R-shaped portion 111, and the area of the portion with a straight shape in the X-axis direction is defined as the straight portion 112. As shown in Figure 2(b)(2), the R-shaped portion 111 is locally smaller in area than the straight portion 112 and is therefore more susceptible to swelling. The R-shaped portion 111, whose area is narrowed by swelling, is prone to the accumulation of phase-separated liquid and particles, which may cause problems in the delivery of liquid through the path 100. As will be described later, by using a partition made of a low-swelling material as shown in this disclosure, it is possible to prevent two-dimensional spatial narrowing and maintain smooth liquid delivery.
[0020] Furthermore, it has been confirmed that even if the R-shaped portion 111 is made into a square shape without the R-shape, problems with liquid delivery will occur. It is thought that the reason for the problems with liquid delivery is that phase-separated liquid and particles accumulate on the corner itself, and that a pseudo-R-shape is formed by the swollen septum.
[0021] (Embodiment) (Microfluidic chip) Figure 3 shows an example of the configuration of the microfluidic chip 1 of this disclosure. Figure 3(a) is a schematic plan view of the microfluidic chip 1 of this embodiment. Figure 3(b) is a schematic cross-sectional view showing a cross-section obtained by cutting the microfluidic chip 1 along line AA shown in Figure 3(a).
[0022] As shown in Figure 3(a), the microfluidic chip 1 comprises an input section 2 for introducing a fluid (e.g., liquid), a flow path 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 path section 3. In the microfluidic chip 1, the upper surface of the flow path section 3 is covered by a cover section 12, and the input section 2 and the output section 4 are through holes provided in the cover section 12. Details of the cover section 12 will be described later. Figure 3(a) shows a case where the cover section 12 is transparent and the flow path section 3 is visible through the cover section 12.
[0023] In the microfluidic chip 1, at least one input section 2 and one output section 4 are provided, and multiple sections of each may be provided. In addition, multiple flow channels 3 may be provided in the microfluidic chip 1, and may have a shape that allows for the merging and separation of fluids introduced from the input section 2.
[0024] Next, the components constituting the channel section 3 in the microfluidic chip 1 will be described. As shown in Figure 3(b), the microfluidic chip 1 comprises a substrate portion 10, a partition wall portion 11 that forms a channel (channel section 3) on the substrate portion 10, and a cover portion 12 that is positioned on the portion of the partition wall portion 11 opposite to the portion in contact with the substrate portion 10 and covers the channel. Furthermore, as will be described later, the partition wall portion 11 and the cover portion 12 are subjected to a hydrophilic treatment and then superimposed and integrated. In other words, the partition wall portion 11 and the cover portion 12 are joined at the interface that has been subjected to the hydrophilic treatment. In the microfluidic chip 1, the channel section 3 through which the fluid introduced from the input portion 2 flows is the region surrounded by the substrate portion 10, the partition wall portion 11, and the cover portion 12. The channel section 3 is defined on a two-dimensional plane by opposing partition wall portions 11 provided on the substrate portion 10 and is covered by the substrate portion 10 and the cover portion 12 positioned opposite the substrate portion 10. In other words, the flow path section 3 is a space composed of a substrate section 10, a partition section 11, and a cover section 12. As shown in Figure 3(a), fluid is introduced into the flow path section 3 from an input section 2 provided in the cover section 12, and the fluid that has flowed through the flow path section 3 is discharged from an output section 4. Although the cover section 12 and the substrate section 10 are arranged opposite each other, in this disclosure, for convenience, the member positioned vertically above when the microfluidic chip 1 is placed will be referred to as the cover section 12, and the member positioned vertically below will be referred to as the substrate section 10. The naming of the cover section 12 and the substrate section 10 is not limited to this case.
[0025] In the microfluidic chip 1 according to this embodiment, no adhesive layer is provided between the substrate portion 10, the partition portion 11, and the lid portion 12. In this embodiment, the substrate portion 10, the partition portion 11, and the lid portion 12 are bonded to each other. Generally, an adhesive layer is a layer containing an adhesive and is used to bond multiple components together. By bonding the substrate portion 10, the partition portion 11, and the lid portion 12 without providing an adhesive layer, the elution of adhesive components into the channel in conventional configurations can be avoided, and the influence on the solution in the channel can be prevented.
[0026] (Circuit board section) The substrate portion 10 is the basic component of the microfluidic chip 1, and the channel portion 3 is formed by the partition portion 11 provided on the substrate portion 10. In other words, the substrate portion 10 and the partition portion 11 can be said to be the main body of the microfluidic chip 1. The substrate portion 10 can be formed from either a light-transmitting material or an opaque material. For example, when detecting and observing the state inside the channel portion 3 (fluid state) by light, a material with excellent transparency to the light used for detection can be used. As a light-transmitting material, glass or resin (inorganic or organic) can be used. As for the glass used as the light-transmitting material forming the substrate portion 10, there are no particular limitations, but examples include quartz glass, borosilicate glass, soda glass, etc. Also, for example, if it is not necessary to detect and observe the state inside the channel portion 3 (fluid state) by light, an opaque material may be used. Examples of opaque materials include silicon wafers and copper plates. As for the material of the substrate portion 10, it is preferable that the degree of swelling in response to organic solvents is 10% or less. More preferably, the swelling is 8% or less, and even more preferably 6% or less. Using such a material makes it possible to achieve smooth liquid delivery of the sample within the microfluidic chip 1. When a material with such swelling is used, the same material as the partition wall portion 11 can also be used for the substrate portion 10. The explanation of transparency and these materials will be given later in the explanation of the partition wall portion 11. Furthermore, the thickness of the substrate portion 10 is not particularly limited, but it is preferably in the range of 0.1 to 1.0 mm.
[0027] (Partition wall) (Transparent resin) The partition wall portion 11 is provided on the substrate portion 10 and is configured to form the flow channel portion 3. The partition wall portion 11 can be formed from, for example, a resin material. Preferably, the material of the partition wall portion 11 has a swelling degree of 10% or less in relation to an organic solvent. More preferably, it is 8% or less, and even more preferably 6% or less. Using such a material makes it possible to achieve smooth delivery of the sample in the microchannel. Preferably, the material of the partition wall portion 11 is transparent. Transparent means that the transmittance is 80% or more, preferably 95% or more, in the entire wavelength range of 400 to 700 nm in the visible light region. Being transparent minimizes the possibility of swelling of the partition wall portion 11 during sample delivery and the possibility of observation being hindered even if elution into the sample occurs. Transparent resins are preferred as transparent materials due to their ease of formation. These transparent resins include thermoplastic resins, thermosetting resins, and photosensitive resins. Furthermore, the transparent resin may, if necessary, use monomers or oligomers that are precursors to the transparent resin and harden upon irradiation to produce a transparent resin, either alone or in a mixture of two or more types. Examples of thermoplastic resins include butyral resin, styrene-(anhydride) maleic acid copolymer, styrene / styrene sulfonic acid copolymer, ethylene / (meth)acrylic acid copolymer, isobutylene / (anhydride) maleic acid copolymer, chlorinated polyethylene, chlorinated polypropylene, polyvinyl chloride, vinyl chloride-vinyl acetate copolymer-polyvinyl acetate, polyurethane resins, polyester resins, acrylic resins, alkyd resins, polystyrene, polyamide resins, rubber resins, cyclic rubber resins, celluloses, polyethylene, polybutadiene, and polyimide resins. Examples of thermosetting resins include epoxy resin, benzoguanamine resin, rosin-modified maleic acid resin, rosin-modified fumaric acid resin, melamine resin, urea resin, and phenolic resin. In this disclosure, the case in which a photosensitive resin is used as the partition wall portion 11 will be described.
[0028] (Photosensitive resin) A photosensitive resin refers to a resin having radical crosslinking properties, and a resin with a mass-average molecular weight of 5,000 to 100,000 having at least one ethylene unsaturated double bond is used as the partition portion 11. Specifically, a resin is used in which a linear polymer having reactive functional groups such as hydroxyl groups, carboxyl groups, and amino groups is reacted with a (meth)acrylic compound or cinnamic acid having reactive functional groups such as isocyanate groups, aldehyde groups, and epoxy groups that can react with the above-mentioned reactive functional groups, thereby introducing ethylene unsaturated double bonds such as (meth)acryloyl groups and styryl groups. Alternatively, a linear polymer containing acid anhydrides such as styrene-maleic anhydride copolymer or α-oleic acid-maleic anhydride copolymer may be used, which has been half-esterified with a (meth)acrylic compound having hydroxyl groups such as hydroxyalkyl (meth)acrylate.
[0029] (Photopolymerizable monomer) The monomers that harden and produce transparent resin upon irradiation as described above are also called photopolymerizable monomers. Photopolymerizable monomers are monomers whose polymerization is induced by radicals. Examples of photopolymerizable monomers and oligomers obtained by polymerizing photopolymerizable monomers that can be used as the partition portion 11 include methyl (meth)acrylate, ethyl (meth)acrylate, 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, cyclohexyl (meth)acrylate, β-carboxyethyl (meth)acrylate, diethylene glycol di(meth)acrylate, glycerol acrylate methacrylate, glycerol dimethacrylate, 1,6-hexanediol di(meth)acrylate, triethylene glycol di(meth)acrylate, tripropylene glycol di(meth)acrylate, 2-hydroxy-3-acryloylpropyl methacrylate, trimethylolpropane di(meth)acrylate, trimethylolpropane tri(meth)acrylate, and ditrimethylolpropane tri(meth)acrylate. Examples include acrylates, pentaerythritol tri(meth)acrylate, 1,6-hexanediol diglycidyl ether di(meth)acrylate, bisphenol A diglycidyl ether di(meth)acrylate, neopentyl glycol diglycidyl ether di(meth)acrylate, dipentaerythritol penta(meth)acrylate, dipentaerythritol hexa(meth)acrylate, dipentaerythritol ethylene oxide-modified penta(meth)acrylate, dipentaerythritol propylene oxide-modified penta(meth)acrylate, dipentaerythritol caprocalactone-modified penta(meth)acrylate, tricyclodecanyl(meth)acrylate, ester acrylates, (meth)acrylic acid esters of methylolated melamine, epoxy(meth)acrylate, urethane acrylate, and various other acrylic acid esters and methacrylic acid esters, reaction products of epoxy group-containing compounds and carboxy(meth)acrylate, hydroxyl group-containing polyol polyacrylate, etc. In addition, (meth)acrylic acid, styrene, vinyl acetate, hydroxyethyl vinyl ether, ethylene glycol divinyl ether, pentaerythritol trivinyl ether, (meth)acrylamide, N-hydroxymethyl(meth)acrylamide, N-vinylformamide, acrylonitrile, etc., can also be used as photopolymerizable monomers that form the partition wall 11. These can be used individually or in combination of two or more types.
[0030] (Polymerization initiator) When curing a composition containing a photosensitive resin and a photopolymerizable monomer (hereinafter also referred to as "resin composition") by ultraviolet irradiation, a photopolymerization initiator or the like is added. As photopolymerization initiators, acetophenone compounds such as 4-phenoxydichloroacetophenone, 4-t-butyl-dichloroacetophenone, diethoxyacetophenone, 1-(4-isopropylphenyl)-2-hydroxy-2-methylpropan-1-one, 1-hydroxycyclohexylphenyl ketone, 2-benzyl-2-dimethylamino-1-(4-morpholinophenyl)-butan-1-one, benzoin compounds such as benzoin, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzyldimethyl ketal, benzophenone, benzoylbenzoic acid, methyl benzoylbenzoate, 4-phenylbenzophenone, hydroxybenzoenone, acrylic benzophenone, 4-benzoyl-4'-methyldiphenyl sulfide, 3,3',4,4'-tetra(t-butylperoxycarbonyl)benzophenone, thioxanthone, 2-chlorthioxanthone, 2- Thioxanthone compounds such as methylthioxanthone, isopropylthioxanthone, 2,4-diisopropylthioxanthone, 2,4-diethylthioxanthone, 2,4,6-trichloro-s-triazine, 2-phenyl-4,6-bis(trichloromethyl)-s-triazine, 2-(p-methoxyphenyl)-4,6-bis(trichloromethyl)-s-triazine, 2-(p-tolyl)-4,6-bis(trichloromethyl)-s-triazine, 2-piperonyl-4,6- Triazine compounds such as bis(trichloromethyl)-s-triazine, 2,4-bis(trichloromethyl)-6-styryl-s-triazine, 2-(naphtho-1-yl)-4,6-bis(trichloromethyl)-s-triazine, 2-(4-methoxynaphtho-1-yl)-4,6-bis(trichloromethyl)-s-triazine, 2,4-trichloromethyl-(piperonyl)-6-triazine, and 2,4-trichloromethyl(4'-methoxystyryl)-6-triazine, 1,Oxime ester compounds such as 2-octanedione, 1-[4-(phenylthio)-,2-(O-benzoyl oxime)], O-(acetyl)-N-(1-phenyl-2-oxo-2-(4'-methoxynaphthyl)ethylidene)hydroxylamine, phosphine compounds such as bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, quinone compounds such as 9,10-phenanthrenequinone, camphorquinone, and ethylanthraquinone, borate compounds, carbazole compounds, imidazole compounds, and titanocene compounds are used. These photopolymerization initiators can be used individually or in combination of two or more. The amount of photopolymerization initiator used is preferably 0.5 to 50% by weight, more preferably 3 to 30% by weight, based on the total solid content of the composition containing the photosensitive resin and photopolymerizable monomer.
[0031] (Photosensitizer) Furthermore, polymerization initiators and photosensitizers can be used in combination. As sensitizers, amine compounds such as α-acyloxime esters, acylphosphine oxides, methylphenylglyoxylates, benzyl, 9,10-phenanthrenequinone, camphorquinone, ethyl anthraquinone, 4,4'-diethylisophthalophenone, 3,3',4,4'-tetra(t-butylperoxycarbonyl)benzophenone, triethanolamine, methyldiethanolamine, triisopropanolamine, methyl 4-dimethylaminobenzoate, ethyl 4-dimethylaminobenzoate, isoamyl 4-dimethylaminobenzoate, 2-dimethylleaminoethyl benzoate, 2-ethylhexyl 4-dimethylaminobenzoate, N,N'-dimethylparatoluidine, 4,4'-bis(dimethylamino)benzophenone, 4,4'-bis(diethylamino)benzophenone, and 4,4'-bis(ethylmethylamino)benzophenone can be used. These sensitizers can be used individually or in combination of two or more. The amount of sensitizer used is preferably 0.5 to 60% by weight, and more preferably 3 to 40% by weight, based on the total amount of the photopolymerization initiator and the sensitizer.
[0032] (solvent) The resin composition may contain an organic solvent as needed to enable uniform coating on the substrate. The solvent also has the function of uniformly dispersing pigments and other admixtures. Suitable organic solvents for use as partitions 11 include, for example, cyclohexanone, ethyl cellosolve acetate, butyl cellosolve acetate, methoxy-2-propyl acetate, diethylene glycol dimethyl ether, propylene glycol monomethyl ether acetate, ethylbenzene, ethylene glycol diethyl ether, xylene, ethyl cellosolve, methyl-n-amyl ketone, propylene glycol monomethyl ether toluene, methyl ethyl ketone, ethyl acetate, methanol, ethanol, isopropyl alcohol, butanol, isobutyl ketone, and petroleum-based solvents. These organic solvents can be used alone or in mixtures.
[0033] (Lid) The lid portion 12 constitutes the flow channel portion 3 by the substrate portion 10 and the partition wall portion 11 on the substrate portion 10. The lid portion 12, like the substrate portion 10, can be formed from either a light-transmitting material or an opaque material. For example, when detecting and observing the state inside the flow channel portion 3 (fluid state) by light, a material with excellent transparency to said light can be used. As a light-transmitting material, glass or resin (inorganic or organic) can be used. As for the glass used as the light-transmitting material forming the lid portion 12, there are no particular limitations, but examples include quartz glass, borosilicate glass, soda glass, etc. As for inorganic resins, examples include silicone resins, etc. As for organic resins, examples include acrylic resins, olefin resins, polycarbonate resins, etc. In this invention, if the degree of swelling of either the lid portion 12 or the substrate portion 10 in relation to an organic solvent is 10% or less, smooth fluid delivery of the sample inside the microfluidic chip 1 can be maintained.
[0034] (Manufacturing method flowchart) (Step S1. Application of photosensitive resin to the substrate) Figure 4 is a flowchart illustrating an example of a method for manufacturing a microfluidic chip. First, as step S1, a photosensitive resin is applied to the substrate portion 10 to form the partition portion 11. This forms a photosensitive resin layer on the substrate portion 10 for forming the partition portion 11. The coating can be performed by methods such as spin coating, spray coating, bar coating, or slit die coating, with slit die coating being preferred from the viewpoint of film thickness controllability. Furthermore, various forms of photosensitive resin, such as liquid, solid, gel, or film, can be applied to the substrate 10. Among photosensitive resins, liquid resist is preferred for ease of handling and other reasons when forming the photosensitive resin layer. Depending on the characteristics of the flow channel pattern, either a positive or negative type of resist can be used as the liquid resist. Furthermore, a photosensitive resin is applied to the substrate portion 10 such that the thickness of the photosensitive resin layer, i.e., the thickness of the partition wall portion 11, is within the range of 1 to 500 μm.
[0035] (Step S2. Pre-bake) After forming a photosensitive resin layer on the substrate portion 10, the next step, as step S2, is to perform a heat treatment (pre-bake treatment) for the purpose of removing the solvent contained in the photosensitive resin. 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 by appropriately setting the conditions (temperature and time) according to the characteristics of the photosensitive resin. In addition, instead of or after the pre-baking process, if necessary, the substrate portion 10 may be treated with HMDS (hexamethyldisilazane) or coated with a thin film of resin in order to improve the adhesion between the lid portion 12 and the photosensitive resin layer on the substrate portion 10 which will become the partition wall portion 11.
[0036] (Step S3. Exposure of the flow path pattern) Next, as step S3, the photosensitive resin layer formed on the substrate portion 10 is exposed. Specifically, a channel pattern is drawn on the photosensitive resin on the substrate portion 10 by exposure. Exposure can be performed, for example, by an exposure apparatus using ultraviolet light as a light source or a laser writing apparatus. Among laser writing apparatuses, exposure using a proximity exposure apparatus or a contact exposure apparatus using ultraviolet light as a light source is preferred from the viewpoint of being able to handle large substrates. In the case of a proximity exposure apparatus, exposure is performed via a photomask having a channel pattern arrangement of the channel portion 3 in the microfluidic chip 1. The photomask can be one such photomask with a light-shielding film of a two-layer structure of chromium and chromium oxide. In step S1, if the photosensitive resin coated on the substrate portion 10 is a positive-type resist, the exposed area dissolves to form the channel portion 3, and the photosensitive resin remaining in the unexposed area becomes the partition wall portion 11. In step S1, if the photosensitive resin coated on the substrate portion 10 is a negative-type resist, the photosensitive resin remaining in the exposed area becomes the partition wall portion 11, and the unexposed area dissolves to form the channel portion 3. Thus, in the manufacturing method of the microfluidic chip 1 according to this embodiment, the partition wall portion 11 constituting the channel portion 3 can be formed on the substrate portion 10 using photolithography. Furthermore, if a chemically amplified resist or the like is used to form the resin layer on the substrate portion 10, it is possible to perform further heat treatment (post-exposure bake: PEB) after exposure to promote the catalytic reaction of the acid generated by exposure.
[0037] (Step S4. Development of the flow path pattern) Next, in step S4, the exposed photosensitive resin layer is developed to form a channel pattern, which is the shape of the channel section 3. Development is performed by reacting the photosensitive resin layer with the developer using a developing device that sprays the developer using methods such as spray, dip, or paddle. The developer can be, for example, an aqueous sodium carbonate solution, tetramethylammonium hydroxide, potassium hydroxide, or an organic solvent. The developer can be appropriately selected according to the characteristics of the photosensitive resin. In addition, the concentration and development time can be appropriately adjusted according to the characteristics of the photosensitive resin.
[0038] (Step S5. Cleaning the flow path pattern) Next, in step S5, the developing solution used for development is removed from the photosensitive resin layer on the substrate 10 by washing. Washing can be performed using a washing device that reacts the washing solution with the photosensitive resin layer by methods such as spraying, showering, or immersion. As the washing water, a suitable washing water for removing the developing solution used in the development process can be appropriately selected from, for example, pure water or isopropyl alcohol. After washing, drying is performed by a spin dryer, IPA vapor dryer, or natural drying.
[0039] (Step S6. Post-bake) Next, in step S6, a heat treatment (post-bake) is performed on the partition wall portion 11 that forms the flow channel pattern, i.e., the flow channel portion 3. Since the photosensitive resin is also heat-reactive, this post-bake treatment accelerates the hardening of the photosensitive resin layer. The temperature and time of the post-bake are set appropriately according to the properties of the photosensitive resin. Furthermore, the post-bake treatment is performed using, for example, a hot plate or an oven. If drying is insufficient during the washing process in step S5, developer solution and moisture from washing may remain in the partition wall 11. Also, solvent that was not removed during the pre-bake treatment in step S2 may remain in the partition wall 11. These can be removed by performing the post-bake treatment.
[0040] (Step S7. Cutting the circuit board) If multiple channel patterns are arranged on the substrate portion 10, step S7 is performed to cut the channel patterns into individual pieces. Cutting methods include diamond cutters and lasers, but are not limited to any particular method.
[0041] (Step S8. Surface modification (hydrophilization treatment)) Next, in step S8, the partition wall portion 11 and lid portion 12 formed on the substrate portion 10 are exposed to light. This exposure process removes the adsorbed layer of organic matter and other substances from the photosensitive resin layer of the partition wall portion 11 and the surface of the lid portion 12, and also makes them hydrophilic, improving adhesion after the heat pressing described later. Exposure can be performed, for example, using an exposure apparatus and a laser writing apparatus that use ultraviolet light as a light source. For the exposure apparatus, exposure using a proximity exposure apparatus or a contact exposure apparatus that uses ultraviolet light as a light source is preferred. Specifically, it is sufficient for the entire surface of the partition wall portion 11 and lid portion 12 to be exposed, with an exposure dose of 2,000 to 15,000 mJ / cm². 2 This is preferable. The wavelength is preferably 100 to 500 nm, and more preferably 150 to 300 nm. Other surface modification treatment methods include plasma treatment, corona discharge treatment, and excimer laser treatment. In this case, the reactivity of the surface of the partition wall portion 11 is improved, and the treatment method can be appropriately selected according to the affinity and adhesive compatibility between the partition wall portion 11 and the lid portion 12.
[0042] (Step S9. Hot pressing (integration)) Next, in step S9, a process is performed to firmly bond and integrate the partition wall portion 11 and the lid portion 12 formed on the substrate portion 10 by heat pressing. The partition wall portion 11 and the lid portion 12 are subjected to hydrophilic treatment before being overlapped and integrated. In the heat pressing method, it is preferable to use a heat press machine or a heat roll machine, for example. By placing the lid portion 12 on the partition wall portion 11 by heat pressing without using adhesive, the elution of adhesive components into the flow path in the conventional configuration can be avoided, and the influence of the solution in the flow path can be prevented. The conditions for joining the partition wall portion 11 and the lid portion 12 are preferably a pressure of 1 to 30 MPa, a temperature of 40 to 170°C, and a pressing time of 1 to 30 min. In particular, the pressure requires careful handling when dealing with materials that have poor elastic deformation and are prone to breakage, such as glass, and it is necessary to select an appropriate pressure depending on the thickness of the glass (the thickness of the glass substrate (substrate portion 10-1) in Figure 6 (described later) (length in the X-axis direction), or the thickness of the glass substrate 13 in Figures 7, 9 to 11).
[0043] (Preparation of the example) Microfluidic chips were fabricated using the above manufacturing method while changing the materials, and the fluid permeability of the microfluidic chips was evaluated.
[0044] (Preparing materials) First, the degree of swelling of five types of materials A to E used for the partition wall 11, lid 12, and substrate 10 was evaluated in advance. Table 1 shows an overview of materials A to E. Note that materials A to E are just examples of materials used for the partition wall 11, lid 12, and substrate 10, and this disclosure is not limited to materials A to E. [Table 1]
[0045] (Preparation of material A (glass)) Let's explain the case of material A.
[0046] (Formation of a pattern for evaluating the degree of swelling) A pattern was formed on a glass substrate (material A) using an etching method. The procedure for forming the pattern (1) to (13) is described below. (1) Preparation of the glass substrate A glass substrate measuring 100 x 100 mm with a thickness of 0.5 mm was used. (2) Preparation of the resist A negative-type resist was used for the photoresist. (3) Resist coating conditions The spin coater was operated at a rotation speed of 1500 rpm for 20 seconds. The rotation speed and time were adjusted so that the resist film thickness after curing was 0.8 μm. (4) Pre-bake (solvent removal) After applying the resist, pre-baking was performed at 120°C for 20 minutes. (5) Exposure A resist placed on a glass substrate was patterned using a photomask. The photomask used had a two-layer structure of chromium and chromium oxide as the light-shielding film. The shape was line / space = 100 μm / 100 μm. Furthermore, a proximity exposure system was used for exposure. The exposure system used a high-pressure mercury lamp as the light source and exposed the image with an i-line cut filter. The exposure dose was 55 mJ / cm². 2 That is the case. (6) Developing A predetermined resist was removed from the glass substrate using a developer (NaOH: 4 parts by weight, pure water: 996 parts by weight) to form a channel structure (the channel structure was patterned). (7) Washing After development, the glass substrate was subjected to a shower wash with ultrapure water. (8) Drying The glass substrate was dried using a spin dryer after cleaning. (9) Soaking A glass substrate on which a resist was placed was immersed in a hydrofluoric acid solution to form a line / space pattern of 100 μm / 100 μm. (10) Exfoliation exposure The entire surface of the glass substrate on which the resist was placed was exposed. The path light intensity was 140 mJ / cm². 2 That is the case. (11) Stripping and cleaning The glass substrate, after exposure, was immersed in a stripping solution for more than one minute to remove any remaining resist. (12) Washing The glass substrate, after being stripped and cleaned, was dried using a spin dryer. (13) Measurement The pattern (glass groove) formed on the glass substrate was measured. The depth of the glass groove, measured using a laser optical microscope (VK8550, Keyence Corporation), was 100 μm.
[0047] (Measurement of swelling degree) The procedure for measuring the degree of swelling (1) to (4) is explained below. (1) The line width of a glass substrate with a pattern for evaluating the degree of swelling was measured. (2) After measuring the line width, the glass substrate was immersed in a lidded petri dish filled with various solvents for 7 days. The solvents used were hydrocarbon compounds, alcohol compounds, and ketone compounds. In this disclosure, the use of three types of solvents, isopropyl alcohol (IPA), methyl ethyl ketone (MEK), and toluene (toluene), will be described as an example. (3) After impregnation for 7 days, the glass substrate was removed from the petri dish and the line width was measured again. (4) The degree of swelling was measured according to the formula: line width after immersion ÷ line width before immersion × 100. The maximum value among the measurement results in each solvent was taken as the degree of swelling of material A. (5) The results for the degree of swelling are shown in Table 1. For the glass substrate, the degree of swelling was 0% for all solvents. In the column for Material A, the maximum value is shown, and for isopropyl alcohol, methyl ethyl ketone, and toluene, the degree of swelling is 0%.
[0048] (Preparation of materials B-D (acrylic)) The cases of materials B to D are described below. A pattern for evaluating the degree of swelling was formed using the following procedure, and the degree of swelling was measured.
[0049] (Formation of a pattern for evaluating the degree of swelling) A photosensitive resin for the partition wall was applied to a glass substrate to form an evaluation pattern. (1) Preparation of the glass substrate A glass substrate measuring 100 x 100 mm with a thickness of 0.5 mm was used. (2) Preparation of the resist A mixture of the following (i) to (iv) was used as the resist. (i) Acrylate resin: 100 parts by weight, (ii) Dipentaerythritol hexaacrylate: 30 parts by weight, (iii) 2-benzyl-2-dimethylamino-1-(4-morpholinophenyl)-butan-1-one: 6 parts by weight, (iv) Diluting solvent: Propylene glycol monomethyl ether acetate: 100 parts by weight (3) Resist coating conditions The resist was applied to a glass substrate using a slit die. The discharge rate and slit width were adjusted so that the cured resist film thickness was 100 μm. (4) Pre-bake (solvent removal) After applying the resist, pre-baking was performed at 90°C for 2 minutes. (5) Exposure A resist placed on a glass substrate was pattern-exposed via a photomask. The photomask used had a two-layer structure of chromium and chromium oxide as the light-shielding film. The pattern had a line / space ratio of 100 μm / 100 μm. Furthermore, a proximity exposure system was used for the exposure. The exposure system used an ultra-high pressure mercury lamp as the light source. The exposure dose was 150 mJ / cm². 2 That is the case. (6) Developing The unexposed portions of the resist on the glass substrate were dissolved using a 2.5% by weight sodium carbonate solution. (7) Washing After development, the glass substrate was subjected to a shower wash with ultrapure water. (8) Drying The glass substrate was dried using a spin dryer after cleaning. (9) Hardening A glass substrate on which the resist was placed was heated at a predetermined temperature for 30 minutes to cure the resist. The temperature was set differently for each material: 230°C for material B, 150°C for material C, and 110°C for material D.
[0050] (Measurement of swelling degree) The same measurement method was used as for material A. However, while measurements were taken on glass grooves formed on the glass substrate for material A, for materials B to D, measurements were taken on patterns formed on the glass substrate for evaluating the degree of swelling. The results of the swelling degree measurements are shown in Table 1. For material B, the swelling degree was 6% for isopropyl alcohol, 2% for methyl ethyl ketone, and 4% for toluene. The maximum value for material B is 6%. Furthermore, regarding material C, the degree of swelling was 8% for isopropyl alcohol, 5% for methyl ethyl ketone, and 8% for toluene. The maximum value for material C is 8%. Furthermore, regarding material E, the degree of swelling was 10% for isopropyl alcohol, 8% for methyl ethyl ketone, and 10% for toluene. The maximum value for material E is 10%.
[0051] (Preparation of material E (silicone material)) Let's explain the case of material E. A pattern for evaluating the degree of swelling was formed using the following procedure, and the degree of swelling was measured. (Mold making) (1) Template substrate A 4-inch silicon wafer was used as the template substrate. (2) Washing and drying The silicon wafers were cleaned using acetone and ethanol. The cleaned silicon wafers were dried on a hot plate at 100°C for 10 minutes. (3) Application A dry silicon wafer was placed in a spin coater by suction. 5 mL of negative-type photoresist was dropped onto the silicon wafer. After removing air bubbles from the photoresist dropped onto the silicon wafer, the silicon wafer was rotated. The rotation speed was adjusted so that the dry thickness, which is the thickness of the photoresist when it dries into a film on the silicon wafer, was 100 μm. (4) Drying and pre-baking A silicon wafer covered with a thin film of photoresist was pre-baked at 65°C for 5 minutes and at 95°C for 40 minutes, after which the silicon wafer was cooled to room temperature. (5) Exposure A chromium thin film of a photomask is brought into contact with a thin film of photoresist formed on a silicon wafer, generating 8.0 mW / cm². 2 The sample was irradiated with ultraviolet light (wavelength: 365nm) for 25 seconds. (6) Primary hardening The silicon wafer was baked at 65°C for 1 minute and then at 95°C for 15 minutes, after which it was cooled to room temperature. (7) Development A silicon wafer and 10 mL of developer were placed in a 120 mm diameter glass petri dish, and development was performed for 10 minutes using a shaker. (8) Washing The photoresist and developer remaining on the silicon wafer were washed with isopropyl alcohol. (9) Secondary curing A silicon wafer was hard baked at 150°C for 20 minutes using a hot plate. A mold was prepared using the above procedure. The pattern formed on the mold has a line / space ratio of 100 μm / 100 μm.
[0052] (Formation of a pattern for evaluating the degree of swelling) (1) Silicone composition A silicone composition was prepared. The main component and curing agent of the silicone elastomer were mixed in a 10:1 (mass ratio). (2) Application A silicone composition was placed on a mold set up in a glass petri dish. (3) Glass substrate A glass substrate (100 x 100 mm, 0.5 mm thick) was used. (4) Arrangement of glass substrates The layers were stacked to form a mold, a silicone composition, and a glass substrate. (5) Hardening After degassing, the laminate of the mold / silicone composition / glass substrate (hereinafter also simply referred to as "laminated product") was heated at 90°C for 1 hour using a hot plate to cure the silicone composition. (6) Peeling By peeling the laminate from the mold, a first base containing polydimethylsiloxane (PDMS) was obtained. Grooves were formed on the surface of the first base exposed by the peeling. The shape of the grooves formed on the first base corresponds to the shape of the pattern in the mold. (7) Measurement The depth of the groove in the first base, measured using a laser optical microscope (VK8550, Keyence Corporation), was 100 μm.
[0053] (3. Measurement of swelling degree) The same measurement method was used as for material A. However, while measurements were taken on the glass grooves formed on the glass substrate for material A, measurements were taken on the pattern formed on the first substrate for material E. The results of the swelling degree measurements are shown in Table 1. For material E, the swelling degree was 8% for isopropyl alcohol, 8% for methyl ethyl ketone, and 12% for toluene. The maximum value for material E is 12%.
[0054] (Evaluation results of fluid permeability) The microfluidic chip 1a shown in Figure 5 was fabricated by combining the prepared materials A to E, and its fluid permeability was evaluated. Figure 5 is a diagram showing an example of the configuration of the microfluidic chip 1a. Figure 5 is a schematic plan view corresponding to Figure 3(a). The microfluidic chip 1a comprises an input section 2a for introducing fluid, a flow channel section 3a through which the fluid introduced from the input section 2a flows, and an output section 4a for discharging fluid from the flow channel section 3a. The line width w of the flow channel section 3a was set to 100 μm. The diameter Φ of the input section 2a and the output section 4a was set to 0.5 mm. In the flow channel section 3a, the distance L1 from the input section 2a to the zigzag section and the distance from the zigzag section to the output section 4a were both set to L1 = 5000 μm. In addition, the width L2 of the zigzag flow channel in the flow channel section 3a was set to 2500 μm.
[0055] Microfluidic chips 1a were fabricated by changing the combination of materials A to E, and these were designated as Examples 1 to 15. Table 2 shows an overview of the configurations of Examples 1 to 15 and the results of the evaluation of their fluid permeability. For example, in Example 1, material B was used for the partition wall portion 11 and material A was used for the substrate portion 10. In Comparative Examples 1 to 5, microfluidic chips 1a were fabricated using material E for the partition wall portion. In all of Examples 1 to 15 and Comparative Examples 1 to 5, silicone (material E) was used for the lid portion.
[0056] For the examples and comparative examples, an organic solvent containing particles was passed from the input section 2a to the output section 4a. Regarding the "Flowability" item in Table 2, the symbol "◎" indicates that there were no problems such as blockage or residual particles in the flow path, the symbol "〇" indicates that some particles remained but flow was still possible without problems, the symbol "△" indicates that particles remained in multiple places but flow was still possible without problems, and the symbol "×" indicates that blockage of the flow path occurred due to particles. The method for evaluating flowability will be described later. In this disclosure, the cases in which toluene and isopropyl alcohol are used as organic solvents will be described. As shown in Examples 1 to 15, when a material with a swelling degree of 10% or less was used for the partition section 11 of any of the organic solvents, flow was possible without problems. On the other hand, as shown in Comparative Examples 1 to 5, when a material with a swelling degree of 12% or more was used for the partition section 11, problems occurred with flow. [Table 2]
[0057] (Manufacturing and evaluation of swelling degree of the examples and comparative examples) Next, the manufacturing methods and methods for evaluating the degree of swelling of the examples and comparative examples will be described in more detail.
[0058] (1. Example 1) (Configuration of Example 1) Figure 6 shows the configuration of the microfluidic chip 1a-1 of Example 1. Figure 6 corresponds to the cross-sectional view in Figure 3(b). The microfluidic chip 1a-1 of Example 1 is formed using acrylic resin with a swelling degree of 6% (material B) for the partition wall portion 11-1, glass material (material A) for the substrate portion 10-1, and silicone (material E) for the lid portion 12-1. Figure 6 shows the case where the lid portion 12-1 is bonded to the substrate portion 10-1 on which the partition wall portion 11-1 is formed (heat pressing).
[0059] (Manufacturing of Example 1) (1) Application of photosensitive resin to the substrate (Step S1 in Figure 4) A glass substrate (100 x 100 mm, 0.5 mm thick) was used as the substrate portion 10-1. Furthermore, a resist was used as the material for the partition wall portion 11-1. As an example, the following mixtures (i) to (iv) were used. (i) Acrylates, 100 parts by weight, (ii) Dipentaerythritol hexaacrylate, 30 parts by weight, (iii) 2-benzyl-2-dimethylamino-1-(4-morpholinophenyl)-butan-1-one, 6 parts by weight, (iv) Diluting solvent: Propylene glycol monomethyl ether acetate, 100 parts by weight Regarding the application conditions for the resist, it was applied to the glass substrate of substrate section 10-1 using a slit die. The discharge amount and slit width were adjusted so that the thickness of the cured resist film was 100 μm. (2) Pre-baking (solvent removal) (Step S2 in Figure 4) After applying the resist, pre-baking was performed at 90°C for 2 minutes. (3) Exposure of the flow path pattern (Step S3 in Figure 4) A resist placed on the glass substrate of substrate portion 10-1 was pattern-exposed via a photomask. The mask used was a photomask with a two-layer structure of chromium and chromium oxide as the light-shielding film. The shape of the flow channel pattern is as shown in the flow channel section 3a in Figure 5. The assumed volume, which is the volume of the space formed by the flow channel section 3a, is 0.85 mm³. 3 That is the case. Furthermore, a proximity exposure system was used for exposure. A high-pressure mercury lamp was used as the light source. The exposure dose was 150 mJ / cm². 2 That is the case. (4) Development of the flow path pattern (Step S4 in Figure 4) The unexposed portions of the resist on the glass substrate were dissolved using a 2.5% by weight sodium carbonate solution. (5) Cleaning of the flow path pattern (Step S5 in Figure 4) After development, the glass substrate was subjected to a shower wash with ultrapure water. (6) Drying The glass substrate was dried using a spin dryer after cleaning. (7) Post-bake (Step S6 in Figure 4) The glass substrate on which the resist was placed was heated at 230°C for 30 minutes to cure the resist. In this way, a partition wall portion 11-1 was formed on the glass substrate. (8) Cutting the circuit board (Step S7 in Figure 4) The portion of the glass substrate where the channel pattern was excessively formed was cut using a diamond cutter. (9) Fabrication of the lid The fabrication of the lid portion 12-1 will now be explained. (i) Preparation of the base material: A 4-inch silicon wafer was used as the base material. (ii) Preparation of main material and curing agent: The main component and curing agent of the silicone elastomer were mixed in a ratio of 10:1 (by mass) to prepare the silicone composition. (iii) Application: A silicone composition was applied to the base material using an applicator so that it would be 1 mm thick after curing. (iv) Curing: After degassing, the base material was heated at 90°C for 1 hour using a hot plate to cure the silicone composition. (v) Peeling: The cured silicone composition was peeled off from the base material to form a lid portion 12-1 containing polydimethylsiloxane (PDMS). (10) Surface modification (Step S8 in Figure 4) Using a batch-type ultraviolet cleaning and modification device, the surfaces contacting the lid portion 12-1 of the partition portion 11-1 and the surfaces of the lid portion 12-1 contacting the partition portion 11-1 were exposed. The exposure dose was 15,000 mJ / cm 2 This was the case. The exposure dose can be set within the range of 1,000 to 20,000 mJ / cm 2 and it is preferable to set it within the range of 2,000 to 15,000 mJ / cm 2 (11) Thermal pressing (step S9 in FIG. 4) The surfaces where the surface modification treatment was performed on the partition portion 11-1 and the lid portion 12-1 were brought into contact with each other. Subsequently, the laminate of the lid portion 12-1, the partition portion 11-1, and the substrate portion 10-1 was heated in an oven at 150°C for 10 minutes under the condition of 10 MPa. The temperature can be set within the range of 50 to 200°C, and it is preferable to set it within the range of 100 to 150°C. Also, the pressure can be set within the range of 1 to 100 MPa, and it is preferable to set it within the range of 10 to 50 MPa. (12) Fabrication of the liquid inlet / outlet (input portion and output portion) Using a biopsy trephine with a diameter of 0.5 mm, openings (holes) were formed in the lid portion 12-1. The openings were formed at the locations of the input portion 2a and the output portion 4a shown in FIG. 3. In this way, the microchannel chip 1a-1 having an acrylic resin as the partition portion 11-1 was fabricated.
[0060] (Evaluation of swelling degree) (1) Preparation of test liquid 1 As the liquid to be fed into the microchannel chip 1a-1, a liquid feeding test liquid (test liquid 1) in which fine particles were dispersed in an organic solvent was prepared. Test liquid 1 is a mixed liquid of the following (i) and (ii). (i) Organic solvent: Toluene (95 parts by weight) (ii) Fine particles: Plastic fine particles (particle size 15.00 μm) (5 parts by weight) (2) Evaluation of the flow path (i) Test liquid 1 was passed through the microchannel chip 1a-1 at 0.1 mL / min (assuming a flow rate of 100 times / min) for 7 days. (ii) Next, the microfluidic tip 1a-1 was washed by passing 0.1 mL / min of particle-free toluene through it for 1 minute. (iii) The curved portion of the microfluidic chip 1a-1 (corresponding to the R-shaped portion 111 in Figure 2) was observed using an optical microscope. The observation results were evaluated using symbols from "◎" to "×". (iv) Regarding the results, as shown in the "Permeable Toluene" item of Example 1 in Table 2, the permeability of the microfluidic tip 1a-1 was "◎". There were no residual particles in the fluid channel section 3a, and the fluid flow was good.
[0061] (2) Preparation of test solution 2 The same evaluation was performed as in (1)(i) above, except that toluene was replaced with isopropyl alcohol. The liquid permeability result was "◎", as shown in the item "Liquid Permeability IPA", just like in the case of toluene.
[0062] (2. Example 2) (Configuration of Example 2) Figure 7 shows the configuration of the microfluidic chip 1a-2 of Example 2. Figure 7 corresponds to the cross-sectional view in Figure 3(b). Example 2 differs from Example 1 in that the substrate portion 10-2 and the partition wall portion 11-2 are made of the same material B. Specifically, the microfluidic chip 1a-2 is formed using acrylic with a swelling degree of 6% (material B) for the partition wall portion 11-2, acrylic with a swelling degree of 6% (material B) for the substrate portion 10-2, and silicone (material E) for the lid portion 12-2. A glass substrate 13 is also placed on the substrate portion 10-2. In the following description, components that are the same as or equivalent to those in Example 1 are denoted by the same reference numerals, and their descriptions are simplified or omitted.
[0063] (Manufacturing of Example 2) In the configuration of Example 2, the substrate portion 10-1 of Example 1 is replaced with a laminate 14 consisting of a glass substrate 13 and a substrate portion 10-2. The method for forming the laminate 14 consisting of the glass substrate 13 and the substrate portion 10-2 will be described below.
[0064] (Laminate 14 of glass substrate 13 and substrate portion 10-2) Figure 8 is a flowchart showing an example of a manufacturing method for a laminate 14 consisting of a glass substrate 13 and a substrate portion 10-2. The laminate 14 consisting of the glass substrate 13 and the substrate portion 10-2 was formed as follows. (1) Preparation of the glass substrate For step S10, a glass substrate 13 (100 x 100 mm, 0.5 mm thick) was used. (2) Preparation of the resist In step S11, a resist was used as the material for the substrate portion 10-2. The following mixtures (i) to (iv) were used. (i) Acrylate resin: 100 parts by weight, (ii) Dipentaerythritol hexaacrylate: 30 parts by weight, (iii) 2-benzyl-2-dimethylamino-1-(4-morpholinophenyl)-butan-1-one: 6 parts by weight, (iv) Diluent solvent: 100 parts by weight Furthermore, regarding the application conditions for the resist, it was applied onto the glass substrate 13 using a slit die. The discharge amount and slit width were adjusted so that the thickness of the cured resist film was 100 μm. (3) Pre-bake (solvent removal) After coating the resist, pre-baking was performed at 90°C for 2 minutes as step S12. Excess solvent contained in the resist was removed. (4) Full exposure of the resist In step S13, the entire surface of the resist formed on the glass substrate 13 was exposed. A proximity exposure apparatus was used for exposure. A high-pressure mercury lamp was used as the light source. The exposure dose was 150 mJ / cm². 2 That is the case. (5) Post-bake In step S14, the exposed glass substrate 13 was heated at 230°C for 30 minutes to cure the resist. Through the above process, a laminate 14 was formed in which the glass substrate 13 and the substrate portion 10-2 were stacked.
[0065] The partition wall portion 11-2 and the lid portion 12-2 are laminated onto the laminated structure 14. The method for forming the partition wall portion 11-2 and the lid portion 12-2 is the same as the method for forming the partition wall portion 11-1 and the lid portion 12-1 in Example 1. The method for fabricating the liquid supply port is also the same as in Example 1.
[0066] (Evaluation of swelling degree) The degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, as in Example 1. For toluene, as shown in the "Permeable Toluene" item in Example 2 of Table 2, the permeability of the microfluidic tip 1a-2 was "○" when toluene was used as the solvent. Similarly, as shown in the "Permeable IPA" item, when isopropyl alcohol was used as the solvent, the permeability was "○" as with toluene.
[0067] (3. Example 3) (Configuration of Example 3) Figure 9 shows the configuration of the microfluidic chip 1a-3 of Example 3. Figure 9 corresponds to the cross-sectional view in Figure 3(b). Example 3 differs from Example 1 in that the substrate portion 10-3 is made of material C, and the substrate portion 10-1 of Example 1 is changed to a laminate 14-3 of substrate portion 10-3 and glass substrate 13. Specifically, the microfluidic chip 1a-3 is formed using acrylic with a swelling degree of 6% (material B) for the partition portion 11-3, acrylic with a swelling degree of 8% (material C) for the substrate portion 10-3, and silicone (material E) for the lid portion 12-3. In addition, a glass substrate 13 is placed on the substrate portion 10-3. In the following description, components that are the same or equivalent as those in Examples 1 and 2 above are denoted by the same reference numerals, and their descriptions are simplified or omitted.
[0068] (Manufacturing of Example 3) In the configuration of Example 3, the laminate 14 of the glass substrate 13 and substrate portion 10-2 in Example 2 is changed to a laminate 14-3 of the glass substrate 13 and substrate portion 10-3. The manufacturing method of the laminate 14-3 is the same as the manufacturing method of the laminate 14 in Example 2 shown in Figure 8. However, in step S14 in Figure 8, the post-bake was performed at 150°C for 30 minutes. Furthermore, the partition wall portion 11-3 and the lid portion 12-3 are laminated onto the laminated structure 14-3. The method for forming the partition wall portion 11-3 and the lid portion 12-3 is the same as the method for forming the partition wall portion 11-1 and the lid portion 12-1 in Example 1. The method for fabricating the liquid supply port is also the same as in Example 1.
[0069] (Evaluation of swelling degree) The degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, as in Example 1. As shown in the "Permeable Toluene" item in Example 3 of Table 2, when toluene was used as the solvent, the permeability of the microfluidic tip 1a-3 was "○". Also, as shown in the "Permeable IPA" item, when isopropyl alcohol was used as the solvent, the permeability of the microfluidic tip 1a-3 was "○".
[0070] (4. Example 4) (Configuration of Example 4) Figure 10 shows the configuration of the microfluidic chip 1a-4 of Example 4. Figure 10 corresponds to the cross-sectional view in Figure 3(b). Example 4 differs from Example 1 in that the substrate portion 10-4 is made of material D, and the substrate portion 10-1 of Example 1 is changed to a laminate 14-4 of substrate portion 10-4 and glass substrate 13. Specifically, the microfluidic chip 1a-4 is formed using acrylic with a swelling degree of 6% (material B) for the partition portion 11-4, acrylic with a swelling degree of 10% (material D) for the substrate portion 10-4, and silicone (material E) for the lid portion 12-4. In addition, a glass substrate 13 is placed on the substrate portion 10-4. In the following description, components that are the same or equivalent as those in Examples 1 to 3 above are denoted by the same reference numerals, and their descriptions are simplified or omitted.
[0071] (Manufacturing of Example 4) In the configuration of Example 4, the laminate 14 of the glass substrate 13 and substrate portion 10-2 in Example 2 is changed to a laminate 14-4 of the glass substrate 13 and substrate portion 10-4. The manufacturing method of the laminate 14-4 is the same as the manufacturing method of the laminate 14 in Example 2 shown in Figure 8. However, in step S14 in Figure 8, the post-bake was performed at 110°C for 30 minutes. Furthermore, the partition wall portion 11-4 and the lid portion 12-4 are laminated onto the laminated structure 14-4. The method for forming the partition wall portion 11-4 and the lid portion 12-4 is the same as the method for forming the partition wall portion 11-1 and the lid portion 12-1 in Example 1. The method for fabricating the liquid supply port is also the same as in Example 1.
[0072] (Evaluation of swelling degree) The degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, as in Example 1. As shown in the "Permeable Toluene" item for Example 4 in Table 2, when toluene was used as the solvent, the permeability of the microfluidic tip 1a-4 was "○". Also, as shown in the "Permeable IPA" item, when isopropyl alcohol was used as the solvent, the result was "○", similar to the case with toluene. (5. Example 5) (Configuration of Example 5) Figure 11 shows the configuration of the microfluidic chip 1a-5 of Example 5. Figure 11 corresponds to the cross-sectional view in Figure 3(b). Example 5 differs from Example 1 in that the substrate portion 10-5 is made of material E, and the substrate portion 10-1 of Example 1 is changed to a laminate 14-5 of substrate portion 10-5 and glass substrate 13. Specifically, the microfluidic chip 1a-5 is formed using acrylic with a moisture content of 6% (material B) for the partition portion 11-5, silicone (swelling content of 12%; material E) for the substrate portion 10-5, and silicone (material E) for the lid portion 12-5. In addition, a glass substrate 13 is placed on the substrate portion 10-5. In the following description, components that are the same or equivalent as those in Examples 1 to 4 above are denoted by the same reference numerals, and their descriptions are simplified or omitted.
[0073] (Manufacturing of Example 5) (Laminate 14-5 of glass substrate 13 and substrate portion 10-5) Figure 12 is a flowchart illustrating an example of a method for manufacturing a laminate 14-5 consisting of a glass substrate 13 and substrate portions 10-5. The laminate 14-5 consisting of the glass substrate 13 and substrate portions 10-5 was formed as follows. (1) Preparation of the glass substrate For step S20, a glass substrate 13 (100 x 100 mm, 0.5 mm thick) was used. (2) Preparation of main material and hardener In step S21, a silicone composition was prepared. The main component and curing agent of the silicone elastomer were mixed in a 10:1 (mass ratio). (3) Application In step S22, the silicone composition was applied to the glass substrate 13. After curing, the silicone composition was applied with an applicator to a thickness of 100 μm. (4) Hardening In step S23, after degassing, the silicone composition was cured by heating the glass substrate 13 at 90°C for 1 hour using a hot plate. (5) Surface modification The silicone composition on the glass substrate 13 is exposed to light. The exposure process removes the adsorbed layer of organic matter and other substances from the surface of the silicone composition, and also generates hydroxyl groups and carbonyl groups, making it hydrophilic. The silicone composition forming the partition wall 11-5 is exposed to ultraviolet light using a batch-type ultraviolet cleaning and modification apparatus. The exposure dose is 15,000 mJ / cm². 2 That's what I decided. Through the above process, a laminate 14-5 was fabricated in which the glass substrate 13 and the substrate portion 10-5 were stacked.
[0074] Furthermore, the partition wall portion 11-5 and the lid portion 12-5 are laminated onto the laminated structure 14-5. The method for forming the partition wall portion 11-5 and the lid portion 12-5 is the same as the method for forming the partition wall portion 11-1 and the lid portion 12-1 in Example 1. The method for fabricating the liquid supply port is also the same as in Example 1.
[0075] (Evaluation of swelling degree) The degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, as in Example 1. As shown in the "Permeable Toluene" item for Example 5 in Table 2, the permeability of microfluidic tip 1a-3 was "△" when toluene was used as the solvent. Also, as shown in the "Permeable IPA" item, the permeability of microfluidic tip 1a-3 was "〇" when isopropyl alcohol was used as the solvent.
[0076] Next, Examples 6 to 15 will be described. Examples 6 to 15 are modified versions of Examples 1 to 5. Therefore, in the following description, the same or equivalent components as those in Examples 1 to 5 will be denoted by the same reference numerals, and their descriptions will be simplified or omitted.
[0077] (6. Example 6) The configuration of Example 6 differs from Example 1 in that the partition wall portion 11-1 is changed to acrylic with a swelling degree of 8% (material C), but the lid portion and substrate portion are the same as in Example 1. Furthermore, the manufacturing process for Example 6 differs in that the baking of the partition wall (corresponding to step 6 in Figure 4) was carried out at 150°C for 30 minutes, but the other manufacturing steps are the same as in Example 1. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As shown in the "Permeable Toluene" and "Permeable IPA" items in Example 6 of Table 2, the permeability of the microfluidic chip in Example 6 was "◎" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0078] (7. Example 7) The configuration of Example 7 differs from Example 2 in that the partition wall portion 11-2 is changed to acrylic with a swelling degree of 8% (material C), but the lid portion and substrate portion are the same as in Example 2. Furthermore, the manufacturing process for Example 7 differs in that the partition wall section (corresponding to step 6 in Figure 4) was baked at 150°C for 30 minutes, but the other manufacturing steps are the same as in Example 2. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As shown in the "Permeable Toluene" and "Permeable IPA" items of Example 7 in Table 2, the permeability of the microfluidic chip in Example 7 was "○" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0079] (8. Example 8) The configuration of Example 8 differs from Example 3 in that the partition wall portion 11-3 is changed to acrylic with a swelling degree of 8% (material C), but the lid portion and substrate portion are the same as in Example 3. Furthermore, the manufacturing process for Example 8 differs in that the partition wall section (corresponding to step 6 in Figure 4) was baked at 150°C for 30 minutes, but the other manufacturing steps are the same as in Example 3. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As shown in the "Permeable Toluene" and "Permeable IPA" items of Example 7 in Table 2, the permeability of the microfluidic chip in Example 8 was "○" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0080] (9. Example 9) The configuration of Example 9 differs from Example 4 in that the partition wall portion 11-4 is changed to acrylic with a swelling degree of 8% (material C), but the lid portion and substrate portion are the same as in Example 4. Furthermore, the manufacturing process for Example 9 differs in that the partition wall section (corresponding to step 6 in Figure 4) was baked at 150°C for 30 minutes, but the other manufacturing steps are the same as in Example 4. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As shown in the "Permeable Toluene" and "Permeable IPA" items for Example 9 in Table 2, the permeability of the microfluidic chip in Example 9 was "○" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0081] (10. Example 10) The configuration of Example 10 differs from Example 5 in that the partition wall portion 11-5 is changed to acrylic with a swelling degree of 8% (material C), but the lid portion and substrate portion are the same as in Example 5. Furthermore, the manufacturing process for Example 5 differs in that the partition wall section (corresponding to step 6 in Figure 4) was baked at 150°C for 30 minutes, but the other manufacturing steps are the same as in Example 5. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, as in Example 1. As shown in the "Permeable Toluene" and "Permeable IPA" items in Example 10 of Table 2, the permeability of Example 10 when toluene was used as the solvent was "△". The permeability of Example 10 when isopropyl alcohol was used as the solvent was "〇".
[0082] (11. Example 11) The configuration of Example 11 differs from Example 1 in that the partition wall portion 11-1 is changed to acrylic with a swelling degree of 10% (material D), but the lid portion and substrate portion are the same as in Example 1. Furthermore, the manufacturing process for Example 11 differs in that the partition wall section (corresponding to step 6 in Figure 4) was baked at 110°C for 30 minutes, but the other manufacturing steps are the same as in Example 1. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As shown in the "Permeable Toluene" and "Permeable IPA" items of Example 11 in Table 2, the permeability of the microfluidic chip in Example 11 was "◎" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0083] (12. Example 12) The configuration of Example 12 differs from Example 2 in that the partition wall portion 11-2 is changed to acrylic with a swelling degree of 10% (material D), but the lid portion and substrate portion are the same as in Example 2. Furthermore, the manufacturing process for Example 12 differs in that the partition wall section (corresponding to step 6 in Figure 4) was baked at 110°C for 30 minutes, but the other manufacturing steps are the same as in Example 2. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As shown in the "Permeable Toluene" and "Permeable IPA" items for Example 12 in Table 2, the permeability of the microfluidic chip in Example 12 was "○" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0084] (13. Example 13) The configuration of Example 13 differs from Example 3 in that the partition wall portion 11-3 is changed to acrylic with a swelling degree of 10% (material D), but the lid portion and substrate portion are the same as in Example 3. Furthermore, the manufacturing process for Example 13 differs in that the partition wall section (corresponding to step 6 in Figure 4) was baked at 110°C for 30 minutes, but the other manufacturing steps are the same as in Example 3. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As shown in the items "Permeable Toluene" and "Permeable IPA" for Example 13 in Table 2, the permeability of the microfluidic chip in Example 13 was "○" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0085] (14. Example 14) The configuration of Example 14 differs from Example 4 in that the partition wall portion 11-4 is changed to acrylic with a swelling degree of 10% (material D), but the lid portion and substrate portion are the same as in Example 4. Furthermore, the manufacturing process for Example 14 differs in that the partition wall section (corresponding to step 6 in Figure 4) was baked at 110°C for 30 minutes, but the other manufacturing steps are the same as in Example 4. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As shown in the "Permeable Toluene" and "Permeable IPA" items of Example 14 in Table 2, the permeability of the microfluidic chip in Example 14 was "○" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0086] (15. Example 15) The configuration of Example 15 differs from Example 5 in that the partition wall portion 11-5 is changed to acrylic with a swelling degree of 10% (material D), but the lid portion and substrate portion are the same as in Example 5. Furthermore, the manufacturing process for Example 15 differs in that the partition wall section (corresponding to step 6 in Figure 4) was baked at 110°C for 30 minutes, but the other manufacturing steps are the same as in Example 5. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, as in Example 1. As shown in the "Permeable Toluene" and "Permeable IPA" items for Example 15 in Table 2, the permeability of Example 15 was "△" when toluene was used as the solvent. When isopropyl alcohol was used as the solvent, the permeability of Example 15 was "〇".
[0087] (16. Comparative Example 1) The configuration of Comparative Example 1 differs from that of Example 1 in that the partition wall portion 11-1 shown in Figure 6 is changed to silicone (material E) with a swelling degree of 12%, but the lid portion and substrate portion are the same as in Example 1. Furthermore, regarding the manufacturing of Example 1, the method of forming the partition wall portion on the substrate portion (corresponding to steps S1 to S6 in Figure 4) is different, but the other processes are the same as in Example 1.
[0088] Figure 13 is a flowchart illustrating an example of a method for forming a partition wall on the substrate. The method for forming a partition wall on the substrate will now be explained. (Mold making) (1) Template substrate (step S30) A 4-inch silicon wafer was used as the template substrate. (2) Washing and drying (Step S31) The silicon wafer, which served as the template substrate, was cleaned using acetone and ethanol. The cleaned silicon wafer was then dried on a hot plate at 100°C for 10 minutes. (3) Application (Step S32) A dry silicon wafer was placed in a spin coater by suction. 5 mL of negative-type photoresist was dropped onto the silicon wafer. After removing air bubbles from the photoresist dropped onto the silicon wafer, the silicon wafer was rotated. The rotation speed was adjusted so that the dry thickness, which is the thickness of the photoresist when it dries into a film on the silicon wafer, was 100 μm. (4) Drying and pre-baking (Step S33) A silicon wafer covered with a thin film of photoresist was pre-baked at 65°C for 5 minutes and then at 95°C for 40 minutes, after which the silicon wafer was cooled to room temperature. (5) Exposure (Step S34) A chromium thin film of a photomask is brought into contact with a thin film of photoresist formed on a silicon wafer, and 8.0 mW / cm² of power is applied to the photoresist thin film. 2 The sample was irradiated with ultraviolet light (wavelength: 365nm) for 25 seconds. (6) Primary curing (Step S35) The silicon wafer was baked at 65°C for 1 minute and then at 95°C for 15 minutes, after which it was cooled to room temperature. (7) Development (Step S36) A silicon wafer and 10 mL of developer were placed in a 120 mm diameter glass petri dish, and then developed for 10 minutes using a shaker. (8) Cleaning (Step S37) The photoresist and developer remaining on the silicon wafer were washed with isopropyl alcohol. (9) Secondary curing (Step S38) A silicon wafer was hard baked at 150°C for 20 minutes using a hot plate. A mold was created using the above procedure. The shape formed on the mold is an inverted version of the pattern shown in Figure 4.
[0089] (Formation of flow channel patterns) (1) Silicone composition (Step S39) A silicone composition was prepared. The main component and curing agent of the silicone elastomer were mixed in a 10:1 (mass ratio). (2) Application (Step S40) A silicone composition was placed on a mold set up in a glass petri dish. (3) Glass substrate (step S41) A glass substrate (100 x 100 mm, 0.5 mm thick) was used. (4) Arrangement of glass substrate (Step S42) The layers were stacked to form a mold, a silicone composition, and a glass substrate. (5) Curing (Step S43) After degassing, the laminate of the mold / silicone composition / glass substrate (hereinafter also simply referred to as "laminated product") was heated at 90°C for 1 hour using a hot plate to cure the silicone composition. (6) Peeling off (Step S44) By peeling off the cured silicone composition from the mold, a partition wall portion and a substrate portion containing polydimethylsiloxane (PDMS) were obtained. Grooves were formed on the surface of the substrate portion exposed by peeling. The shape of the grooves corresponds to the shape of the pattern in the mold. (7) Measurement The groove depth, measured using a laser optical microscope (VK8550, Keyence Corporation), was 100 μm.
[0090] The partition wall and substrate formed as described above were subjected to substrate cutting (step S7 in Figure 4) followed by heat pressing of the lid (step S9 in Figure 4) to produce the microfluidic chip of Comparative Example 1. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As shown in the "Permeable Toluene" and "Permeable IPA" items of Comparative Example 1 in Table 2, the permeability of the microfluidic chip of Comparative Example 1 was "×" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0091] (17. Comparative Example 2) (Configuration of Comparative Example 2) The configuration of Comparative Example 2 differs from that of Example 2 in that the partition wall portion 11-2 shown in Figure 7 is changed to silicone (material E) with a swelling degree of 12%, but the lid portion and substrate portion are the same as in Example 2.
[0092] (Manufacturing of Comparative Example 2) Furthermore, the manufacturing process for Comparative Example 2 differs in the step of forming the partition wall portion on the substrate (corresponding to steps S1 to S6 in Figure 4). In Comparative Example 2, first, a laminate 14 of the glass substrate 13 of Example 2 and acrylic (material B) with a swelling degree of 6% is prepared as shown in Figure 7. Next, steps S30 to S41 in Figure 13 are omitted, and in step S42 of Figure 13, the mold / silicone composition / laminated product 14 is formed. Subsequently, steps S43 and S44 of Figure 13 are performed to form a silicone (material E) partition in the laminate 14.
[0093] The partition wall and substrate formed as described above were subjected to substrate cutting (step S7 in Figure 4) followed by hot pressing of the lid (step S9 in Figure 4) to produce the microfluidic chip of Comparative Example 2. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As indicated in the "Permeable Toluene" and "Permeable IPA" items in Comparative Example 2 of Table 2, the permeability of the microfluidic chip in Comparative Example 2 was "×" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0094] (18. Comparative Example 3) (Configuration of Comparative Example 3) Comparative Example 3 differs from Example 3 in that the partition wall portion 11-3 shown in Figure 9 is made of silicone (material E) with a swelling degree of 12%, but the lid portion and substrate portion are the same as in Example 3.
[0095] (Manufacturing of Comparative Example 3) Furthermore, the manufacturing process for Comparative Example 3 differs in that it involves forming a partition wall on the substrate (corresponding to steps S1 to S6 in Figure 4). In Comparative Example 3, first, a laminate 14-3 of the glass substrate 13 and acrylic (material) with a swelling degree of 8% as shown in Figure 9 of Example 3 is prepared. Next, steps S30 to S41 in Figure 13 are omitted, and in step S42 of Figure 13, the mold / silicone composition / laminated product 14-3 is formed. Subsequently, steps S43 and S44 of Figure 13 are performed to form a silicone (material E) partition wall in the laminate 14-3.
[0096] The partition wall and substrate formed as described above were subjected to substrate cutting (step S7 in Figure 4) followed by hot pressing of the lid (step S9 in Figure 4) to produce the microfluidic chip of Comparative Example 3. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As shown in the "Permeable Toluene" and "Permeable IPA" items of Comparative Example 3 in Table 2, the permeability of the microfluidic chip in Comparative Example 3 was "×" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0097] (19. Comparative Example 4) (Composition of Comparative Example 4) Comparative Example 4 differs from Example 4 in that the partition wall portion 11-4 shown in Figure 10 is made of silicone (material E) with a swelling degree of 12%, but the lid portion and substrate portion are the same as in Example 3.
[0098] (Manufacturing of Comparative Example 4) Furthermore, the manufacturing process for Comparative Example 4 differs in that it involves forming a partition wall on the substrate (corresponding to steps S1 to S6 in Figure 4). In Comparative Example 4, first, a laminate 14-4 of the glass substrate 13 and acrylic (material D) with a swelling degree of 10% as shown in Figure 10 of Example 4 is prepared. Next, steps S30 to S41 in Figure 13 are omitted, and in step S42 of Figure 13, the mold / silicone composition / laminated product 14-4 is formed. Subsequently, steps S43 and S44 of Figure 13 are performed to form a silicone (material E) partition wall in the laminate 14-4.
[0099] The partition wall and substrate formed as described above were subjected to substrate cutting (step S7 in Figure 4) followed by hot pressing of the lid (step S9 in Figure 4) to produce the microfluidic chip of Comparative Example 4. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As shown in the items "Permeable Toluene" and "Permeable IPA" in Comparative Example 4 of Table 2, the permeability of the microfluidic chip in Comparative Example 4 was "×" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0100] (20. Comparative Example 5) (Composition of Comparative Example 5) Comparative Example 5 differs from Example 5 in that the partition wall portion 11-5 shown in Figure 11 is made of silicone (material E) with a swelling degree of 12%, but the lid portion and substrate portion are the same as in Example 5.
[0101] (Manufacturing of Comparative Example 5) Furthermore, the manufacturing process for Comparative Example 5 differs in that it involves forming a partition wall on the substrate (corresponding to steps S1 to S6 in Figure 4). In Comparative Example 5, first, a laminate 14-5 of the glass substrate 13 and silicone (material E) with a swelling degree of 12% as shown in Figure 11 of Example 5 is prepared. The preparation method is the same as the method shown in the flowchart in Figure 12. Next, steps S30 to S41 in Figure 13 are omitted, and in step S42 of Figure 13, the mold / silicone composition / laminated product 14-5 is formed. Subsequently, steps S43 and S44 of Figure 13 are performed to form a partition wall of silicone (material E) in the laminate 14-5.
[0102] The partition wall and substrate formed as described above were subjected to substrate cutting (step S7 in Figure 4) followed by heat pressing of the lid (step S9 in Figure 4) to produce the microfluidic chip of Comparative Example 5. Furthermore, the degree of swelling was evaluated using test solution 1 containing toluene and test solution 2 containing isopropyl alcohol, similar to Example 1. As shown in the items "Permeable Toluene" and "Permeable IPA" for Comparative Example 5 in Table 2, the permeability of the microfluidic chip in Comparative Example 5 was "×" regardless of whether toluene or isopropyl alcohol was used as the solvent.
[0103] In this disclosure, we have shown cases where hydrocarbon compounds and alcohol compounds were used as organic solvents. However, when ketone compounds were used as organic solvents, the liquid permeability was good and liquid flow was possible without any problems in all of the microfluidic chips of Examples 1 to 15.
[0104] (Effects / Actions) As described above, this disclosure makes it possible to improve the organic solvent resistance of microfluidic chips.
[0105] Although embodiments of the present invention have been described above, the present invention is not limited to the embodiments described above, and various modifications are possible without departing from the spirit of the invention.
[0106] The following describes, but is not limited to, embodiments that may constitute the present invention. (Aspect 1) The circuit board section, A partition wall portion that forms a flow channel on the substrate portion, The partition wall portion is positioned on the side opposite to the portion in contact with the substrate portion, and includes a cover portion that covers the flow path, The partition wall portion is formed of a photosensitive resin having radical crosslinking properties. Microfluidic chip. (Aspect 2) A microfluidic chip according to Embodiment 1, The partition wall and the lid are joined at an interface that has been treated to be hydrophilic. Microfluidic chip. (Aspect 3) A microfluidic chip according to Embodiment 1 or Embodiment 2, The degree of swelling of at least one of the substrate portion, the partition portion, and the lid portion in relation to an organic solvent is less than 10%. Microfluidic chip. (Aspect 4) A microfluidic chip according to any one of embodiments 1 to 3, The aforementioned organic solvent is one of the following: a hydrocarbon compound, an alcohol compound, or a ketone compound. Microfluidic chip. (Appendix 5) A microfluidic chip according to any one of embodiments 1 to 4, The aforementioned photosensitive resin is a liquid resist. The partition wall portion is formed using photolithography. Microfluidic chip. (Aspect 6) A microfluidic chip according to any one of embodiments 1 to 5, The aforementioned hydrophilization treatment is a treatment in which the partition wall portion is exposed to ultraviolet light. Microfluidic chip. (Aspect 7) A microfluidic chip according to any one of embodiments 1 to 6, The aforementioned flow path includes a winding path, Microfluidic chip. (Pattern 8) The circuit board section, A partition wall portion that forms a flow channel on the substrate portion, A method for manufacturing a microfluidic chip comprising a lid portion disposed on the side of the partition wall portion opposite to the substrate portion and covering the flow path, The partition wall and the lid are subjected to a hydrophilic treatment. The hydrophilic treated partition wall and the lid are superimposed and integrated. A method for manufacturing a microfluidic chip that includes steps. (Aspect 9) A method for manufacturing a microfluidic chip according to embodiment 8, A liquid resist is applied to the substrate portion. The partition wall is formed using photolithography. The partition wall portion is exposed to ultraviolet light to perform the hydrophilization treatment. A method for manufacturing a microfluidic chip, further including steps. (Aspect 10) A method for manufacturing a microfluidic chip according to embodiment 8 or embodiment 9, The aforementioned flow path includes a winding path, A method for manufacturing microfluidic chips. [Explanation of Symbols]
[0107] 1, 1a, 1a-1~1a-5: Microfluidic chips 2, 2a: Input section 3, 3a: Flow channel section 4, 4a: Output section 10, 10-1~10-5: Circuit board section 11, 11-1~11-5: Partition wall part 12, 12-1~12-5: Lid part 13: Glass substrate 14, 14-3~14-5: Laminates 100: Route
Claims
1. The circuit board section, A partition wall portion that forms a flow channel on the substrate portion, The partition wall portion is positioned on the side opposite to the portion in contact with the substrate portion, and includes a cover portion that covers the flow path, The partition wall portion is formed of a photosensitive resin having radical crosslinking properties. Microfluidic chip.
2. A microfluidic chip according to claim 1, The partition wall and the lid are joined at an interface that has been treated to be hydrophilic. Microfluidic chip.
3. A microfluidic chip according to claim 1, The degree of swelling of at least one of the substrate portion, the partition portion, and the lid portion in relation to the organic solvent is less than 10%. Microfluidic chip.
4. A microfluidic chip according to claim 3, The aforementioned organic solvent is one of the following: a hydrocarbon compound, an alcohol compound, or a ketone compound. Microfluidic chip.
5. A microfluidic chip according to claim 2, The aforementioned photosensitive resin is a liquid resist. The partition wall portion is formed using photolithography. Microfluidic chip.
6. A microfluidic chip according to claim 2, The aforementioned hydrophilization treatment is a treatment in which the partition wall portion is exposed to ultraviolet light. Microfluidic chip.
7. The microfluidic chip according to claim 1, The aforementioned flow path includes a winding path, Microfluidic chip.
8. The circuit board section, A partition wall portion that forms a flow channel on the substrate portion, A method for manufacturing a microfluidic chip comprising a lid portion disposed on the side of the partition wall portion opposite to the substrate portion and covering the flow path, The partition wall and the lid are subjected to a hydrophilic treatment. The hydrophilic treated partition wall and the lid are superimposed and integrated. A method for manufacturing a microfluidic chip that includes steps.
9. A method for manufacturing a microfluidic chip according to claim 8, A liquid resist is applied to the substrate portion. The partition wall is formed using photolithography. The partition wall portion is exposed to ultraviolet light to perform the hydrophilization treatment. A method for manufacturing a microfluidic chip, further including steps.
10. A method for manufacturing a microfluidic chip according to claim 8, The aforementioned flow path includes a winding path, A method for manufacturing microfluidic chips.