Microfluidic chip and method for manufacturing the same

Abstract

To provide a microfluidic chip that suppresses fluid contamination and flow path clogging. [Solution] The present invention relates to a microfluidic chip comprising a first resin substrate and a second resin substrate, wherein the first resin substrate has a surface A, and a flow channel portion is provided on surface A, the second resin substrate has a surface B opposite to surface A, and surface B covers the flow channel portion, surface A and surface B are directly joined by a joint portion formed along the flow channel portion, the flow channel portion and the joint portion are separated by a flow channel separation portion provided in the plane direction of surface A, and the flow channel separation portion and surface B are in contact or close proximity.

Description

[Technical Field]

[0001] The present invention relates to a microfluidic chip and a method for manufacturing the same. [Background technology]

[0002] Microfluidic chips, which utilize microfabrication technology to form microchannels and reaction vessels on a micrometer scale, are being used in a variety of fields, including DNA testing, biomaterial analysis, drug discovery and development, organic synthesis, and water quality analysis.

[0003] The above-described microfluidic chip can be obtained, for example, by joining a resin fluidic substrate having a fluid channel section to a resin cover substrate covering the fluid channel section. Here, as a method for joining the fluidic substrate and the cover substrate, for example, methods such as bonding using an organic adhesive, or bonding using vibration welding technology or ultrasonic bonding technology can be used (Patent Document 1, etc.). [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] Japanese Patent Publication No. 2002-139419 [Overview of the project] [Problems that the invention aims to solve]

[0005] However, microfluidic chips using organic adhesives may leach out of the adhesive and contaminate the fluid within the channel. Furthermore, since joining using vibration welding or ultrasonic bonding technology joins the entire surface of the channel substrate and the lid substrate, there is a risk that molten resin components may spill into the channel and clog it.

[0006] Therefore, the present invention aims to provide a microfluidic chip in which fluid contamination and clogging of the flow path are suppressed. Furthermore, the present invention aims to provide a method for manufacturing the microfluidic chip described above. [Means for solving the problem]

[0007] The inventors diligently conducted research with the aim of solving the above problems. The inventors found that the above problems can be solved if a microfluidic chip is provided in which a first resin substrate having a flow channel and a second resin substrate are directly joined by a predetermined joint, and the joint and the flow channel are separated by a predetermined flow channel separation portion, and thus the inventors completed the present invention.

[0008] In other words, the present invention aims to advantageously solve the above problems, [1] The present invention is a microfluidic chip comprising a first resin substrate and a second resin substrate, wherein the first resin substrate has a surface A, and a flow channel portion is provided on surface A, the second resin substrate has a surface B opposite to surface A, and surface B covers the flow channel portion, surface A and surface B are directly joined by a joint portion formed along the flow channel portion, the flow channel portion and the joint portion are separated by a flow channel separation portion provided in the plane direction of surface A, and the flow channel separation portion and surface B are in contact or close proximity, the microfluidic chip. With a microfluidic chip like the one described above, fluid contamination and blockage of the flow path can be suppressed. In this specification, "direct bonding" means that two resin substrates are joined without the use of an adhesive or other layer. For example, this can be achieved by joining the A-side of the first resin substrate and the B-side of the second resin substrate using laser light while they are in contact. In this specification, "proximity" means that the shortest distance between two opposing surfaces is greater than 0 μm and 20 μm or less. For example, "the channel separation portion and surface B are in proximity" means that the shortest distance between the channel separation portion and surface B is greater than 0 μm and 20 μm or less. In this specification, "contact" means that the shortest distance between two opposing surfaces is 0 μm, but the two opposing surfaces are not joined. For example, "the channel separation portion and surface B are in contact" means that the shortest distance between the channel separation portion and surface B is 0 μm, but the channel separation portion and surface B are not joined.

[0009] [2] In the microfluidic chip described in [1] above, the first resin substrate and the second resin substrate are preferably made of a cyclic olefin resin. If the first and second resin substrates are made of cyclic olefin resins, the decrease in bonding strength over time due to moisture absorption and the decrease in optical stability are minimized, resulting in a microfluidic chip with excellent durability.

[0010] [3] In the microfluidic chip described in [1] or [2] above, the shortest width of the joint formed along the fluid channel is preferably 0.1 mm or more and 8.0 mm or less. If the shortest width of the above-mentioned joint is greater than or equal to the lower limit, the pressure resistance of the microfluidic chip can be effectively improved. On the other hand, if the shortest width of the joint is less than or equal to the upper limit, the performance of the microfluidic chip can be effectively improved.

[0011] [4] In any of the microfluidic chips described in [1] to [3] above, it is preferable that the ratio of the planar area of ​​the joint formed along the fluid channel to the planar area of ​​the fluid channel separation portion is 200% or more. If the above ratio is above the above lower limit, the leakage resistance and pressure resistance of the microfluidic chip can be effectively improved.

[0012] [5] In any of the microfluidic chips described in [1] to [4] above, the minimum width of the channel separation portion is preferably 100 μm or more and 400 μm or less. If the shortest width of the channel separation section is greater than or equal to the lower limit mentioned above, clogging of the channel in the microfluidic chip can be effectively suppressed. On the other hand, if the shortest width of the flow path separation part is below the above upper limit, the leak resistance and pressure resistance of the micro flow path chip can be effectively improved.

[0013] Moreover, this invention aims to advantageously solve the above problems, and [6] This invention is a method for manufacturing a micro flow path chip according to any one of the above [1] to [5], which includes a bonding process of forming the bonding part using laser light, and is a method for manufacturing a micro flow path chip. With the method for manufacturing a micro flow path chip as described above, a micro flow path chip with suppressed fluid contamination and clogged flow paths can be obtained.

[0014] [7] In the method for manufacturing a micro flow path chip according to [6] above, the wavelength of the laser light is preferably 1.8 μm or more and 40.0 μm or less. If the wavelength of the laser light is within the above range, the appearance of the obtained micro flow path chip can be maintained well.

[0015] [8] In the method for manufacturing a micro flow path chip according to [6] or [7] above, the spot diameter of the laser light is preferably 0.1 mm or more and 8.0 mm or less. If the spot diameter of the laser light is above the above lower limit, the pressure resistance of the obtained micro flow path chip can be effectively improved. On the other hand, if the spot diameter of the laser light is below the above upper limit, clogging of the obtained micro flow path chip can be effectively suppressed. Also, since clogging of the flow path of the obtained micro flow path chip can be effectively suppressed, the leak resistance and pressure resistance of the micro flow path chip can be effectively improved.

Effects of the Invention

[0016] According to the present invention, a micro flow path chip with suppressed fluid contamination and clogged flow paths can be provided. Also, according to the present invention, a method for manufacturing the above-described micro flow path chip can be provided.,

Brief Description of the Drawings

[0017] [Figure 1] A schematic perspective view showing an example of the microfluidic chip of the present invention. [Figure 2] Figure 1 is a schematic cross-sectional view showing the XX cross-section of the microfluidic chip. [Figure 3] Figure 2 is a schematic cross-sectional view showing the YY cross-section of the microfluidic chip. [Figure 4] This is a schematic cross-sectional view showing an example of a channel section and a connecting section when the microfluidic chip of the present invention has multiple channel sections. [Figure 5] This is a schematic cross-sectional view showing an example of a channel section and a connecting section when the microfluidic chip of the present invention has multiple channel sections. [Figure 6] This is a schematic cross-sectional view showing an example of a channel section and a joint section when the microfluidic chip of the present invention has a branched channel section. [Figure 7] This is a schematic cross-sectional view showing an example of a channel section and a joint section when the microfluidic chip of the present invention has a branched channel section. [Modes for carrying out the invention]

[0018] Embodiments of the present invention will be described in detail below. Here, the microfluidic chip of the present invention is a microfluidic chip made of resin. Furthermore, the microfluidic chip of the present invention is not particularly limited and can be used in various fields such as DNA testing, biomaterial analysis, drug discovery and development, organic synthesis, and water quality analysis. The microfluidic chip of the present invention can be obtained by the method for manufacturing a microfluidic chip described later.

[0019] (Microfluidic chip) The microfluidic chip of the present invention comprises a first resin substrate and a second resin substrate. In the microfluidic chip of the present invention, the first resin substrate has a surface A, on which a flow channel is provided, and the second resin substrate has a surface B opposite to surface A, on which surface B covers the flow channel. Surfaces A and B are directly joined by a joint formed along the flow channel, and the flow channel and the joint are separated by a flow channel separation portion provided in the plane direction of surface A, and the flow channel separation portion and surface B are in contact or close proximity. With a microfluidic chip like the one described above, fluid contamination and blockage of the flow path can be suppressed. Furthermore, the microfluidic chip of the present invention may have an end portion at the end of the fluid channel portion of the first resin substrate. A joint portion may also be formed along the end portion, and the end portion and the joint portion may be separated by an end separation portion provided in the plane direction of surface A.

[0020] The microfluidic chip of the present invention will now be described in detail with reference to Figures 1-3, however, the microfluidic chip of the present invention is not limited to those shown in Figures 1-3. Figure 1 is a schematic perspective view showing an example of the microfluidic chip of the present invention, Figure 2 is a schematic cross-sectional view showing the XX cross-section of the microfluidic chip shown in Figure 1, and Figure 3 is a schematic cross-sectional view showing the YY cross-section of the microfluidic chip shown in Figure 2.

[0021] The microfluidic chip 10 shown in Figure 1 comprises a first resin substrate 11 and a second resin substrate 12 located on the first resin substrate 11. The second resin substrate 12 has a through-hole 13 that serves as an injection port for fluids such as samples into the flow channel portion (not shown in Figure 1) of the first resin substrate 11. Here, as shown in Figure 2, the first resin substrate 11 has a surface A 111, on which a flow channel 14 is provided. The second resin substrate 12 has a surface B 121 facing surface A 111, and surface B 121 covers the flow channel 14. Surface A 111 and surface B 121 are directly joined by a joint 15, and the flow channel 14 and the joint 15 are separated by a flow channel separation portion 16 provided in the plane direction of surface A 111, with the flow channel separation portion 16 and surface B 121 in contact. In Figure 2, the flow channel separation portion 16 and surface B 121 are in contact, but they may be close to each other. More specifically, as shown in Figure 3, the joint portion 15 is formed to follow the flow channel portion 14, and the flow channel portion 14 and the joint portion 15 are separated by a flow channel separation portion 16 provided in the plane direction of surface A 111. Here, the first resin substrate 11 has an end portion 17 at the end of the flow channel portion 14. The joint portion 15 is also formed to follow the end portion 17, and the end portion 17 and the joint portion 15 are separated by an end separation portion 18 provided in the plane direction of surface A 111. That is, the joint portion 15 is formed in an annular shape to follow the flow channel portion 14 and the end portion 17, the flow channel portion 14 and the joint portion 15 are separated by a flow channel separation portion 16 provided in the plane direction of surface A 111, and the end portion 17 and the joint portion 15 are separated by an end separation portion 18 provided in the plane direction of surface A 111. Although not shown in the diagram, the end separation portion 18 and surface B 121 may be in contact or in close proximity. Furthermore, although not shown in the diagram, the position of the through-hole 13 in the second resin substrate 12 may correspond to the position of the end 17 of the first resin substrate 11. That is, the through-hole 13 in the second resin substrate may communicate with the corresponding end 17 of the first resin substrate.

[0022] Here, the shortest width of the joint formed along the flow channel (i.e., the joint in contact with the flow channel separation portion, which corresponds to the area between the two dashed lines in Figure 3) is preferably 0.1 mm or more, more preferably 0.5 mm or more, preferably 8.0 mm or less, more preferably 4.0 mm or less, and even more preferably 1.5 mm or less. If the shortest width of the above-mentioned joint is greater than or equal to the lower limit, the pressure resistance of the microfluidic chip can be effectively improved. On the other hand, if the shortest width of the joint is less than or equal to the upper limit, the performance of the microfluidic chip can be effectively improved.

[0023] The minimum width of the channel separation portion is preferably 100 μm or more, more preferably 150 μm or more, preferably 400 μm or less, and more preferably 300 μm or less. If the shortest width of the channel separation section is greater than or equal to the lower limit mentioned above, clogging of the channel in the microfluidic chip can be effectively suppressed. On the other hand, if the shortest width of the channel separation is less than or equal to the above upper limit, the pressure resistance of the microfluidic chip can be effectively improved.

[0024] The ratio of the planar area of ​​the joint formed along the flow path to the planar area of ​​the non-flow path on surface A (planar area of ​​the joint formed along the flow path / planar area of ​​the non-flow path on surface A) is preferably 2.5% or more. If the above ratio is above the above lower limit, the leakage resistance and pressure resistance of the microfluidic chip can be effectively improved. On the other hand, the above ratio may be, for example, 30.0% or less, or 20.0% or less. In this specification, "non-flow channel" means any part other than the flow channel and any end.

[0025] The ratio of the planar area of ​​the joint formed along the flow path to the planar area of ​​the flow path separation portion (planar area of ​​the joint formed along the flow path / planar area of ​​the flow path separation portion) is preferably 100% or more, and more preferably 200% or more. If the above ratio is above the above lower limit, the leakage resistance and pressure resistance of the microfluidic chip can be effectively improved. On the other hand, the above ratio may be, for example, 1500% or less, or even 1000% or less.

[0026] <First resin substrate> The first resin substrate has a surface A, and a channel section is provided on surface A. That is, the first resin substrate can function as a channel substrate for a microfluidic chip. The first resin substrate is typically provided with multiple ends located at the end of the flow channel, which can communicate with the through-holes of the second resin substrate when it is in the state of a microfluidic chip.

[0027] Here, the width, depth, and shape of the channel can be appropriately changed depending on the application of the microfluidic chip, but are usually on the order of millimeters or less, and may be on the order of nanometers, but are preferably on the order of micrometers. The width of the channel is not particularly limited and can be, for example, 10 μm or more and 800 μm or less. The shape of the channel is not particularly limited and may be, for example, a straight shape, a bent shape, etc.

[0028] In one embodiment of the present invention, surface A may be provided with a plurality of flow channels. When a plurality of flow channels exist on surface A, the joint portion only needs to be formed on the outside of the flow channels so as to be in line with the flow channels located on the outside in the surface direction of surface A. However, from the viewpoint of leak resistance, it is preferable that the joint portion is formed along all of the flow channels.

[0029] Here, specific examples of microfluidic chips with multiple flow channels on side A will be explained using Figures 4 and 5, but the microfluidic chips of the present invention are not limited to these. Figures 4 and 5 are schematic cross-sectional views showing examples of flow channels and junctions when the microfluidic chip of the present invention has multiple flow channels.

[0030] In Figure 4, the A-side 111 of the first resin substrate 11 is provided with a first flow channel 141, a second flow channel 142, a third flow channel 143, and a fourth flow channel 144. In Figure 4, the joint 15 is formed outside the first flow channel 141 and the fourth flow channel 144, respectively, so as to be aligned with the first flow channel 141 and the fourth flow channel 144, which are located on the outside in the planar direction of the A-side 111. The first flow channel 141 and the joint 15 are separated by a first flow channel separation portion 161 provided in the planar direction of the A-side 111, and the fourth flow channel 144 and the joint 15 are separated by a fourth flow channel separation portion 164 provided in the planar direction of the A-side 111. Furthermore, the joint portion 15 is formed to partially follow the first end portion 171 to the fourth end portion 174, and the first end portion 171 to the fourth end portion 174 and the joint portion 15 are separated by the first end separation portion 181 to the fourth end separation portion 184, which are provided in the plane direction of surface A 111.

[0031] In Figure 5, the A-side 111 of the first resin substrate 11 is provided with a first flow channel 141, a second flow channel 142, a third flow channel 143, and a fourth flow channel 144. In Figure 5, the first joint 151 to the fourth joint 154 are formed to align with the first to fourth flow channel 141 to the fourth flow channel 144, respectively. That is, the joints are formed to align with all the flow channels. The first to fourth flow channel 141 to the fourth flow channel 144 and the first to fourth joint 151 to the fourth joint 154 are separated by the first to fourth flow channel separation sections 161 to the fourth flow channel separation sections 164, respectively, which are provided in the plane direction of the A-side 111. Furthermore, the first joint portion 151 to the fourth joint portion 154 are formed to follow the first end portion 171 to the fourth end portion 174, and the first end portion 171 to the fourth terminal 174 and the first joint portion 151 to the fourth joint portion 154 are separated by the first end separation portion 181 to the fourth end separation portion 184, which are provided in the plane direction of surface A 111.

[0032] In one embodiment of the present invention, the flow path may be branched. If the flow path is branched, the joint may be formed on the outside of the flow path so as to be along the outermost of the branched flow path sections. However, from the viewpoint of leak resistance, it is preferable that the joint be formed so as to be along all of the branched flow path sections.

[0033] Here, specific examples of microfluidic chips with branched flow channels will be explained using Figures 6 and 7, but the microfluidic chips of the present invention are not limited to these. Figures 6 and 7 are schematic cross-sectional views showing an example of a flow channel and a junction when the microfluidic chip of the present invention has branched flow channels.

[0034] In Figure 6, a branched flow channel 14 is provided on surface A 111 of the first resin substrate 11. In Figure 6, the joint 15 is formed on the outside of each of the two flow channel sections 14, which are located on the outside in the planar direction of surface A 111. The two outer flow channel sections 14 and the joint 15 are separated by flow channel separation sections 16 provided in the planar direction of surface A 111. The joint 15 is also formed along the end 17, and the end 17 and the joint 15 are separated by an end separation section 18 provided in the planar direction of surface A 111.

[0035] In Figure 7, branched flow channels 14 are provided on surface A 111 of the first resin substrate 11. In Figure 7, the joint 15 is formed to follow all of the flow channels 14, and the flow channels 14 and the joint 15 are separated by flow channel separation portions 16 provided in the plane direction of surface A 111. The joint 15 is also formed to follow the end 17, and the end 17 and the joint 15 are separated by an end separation portion 18 provided in the plane direction of surface A 111.

[0036] Optionally, one or more columnar micropillars extending toward the second resin substrate may be joined to the bottom of the flow channel section of the first resin substrate. A micropillar is a device that changes the flow of particles depending on the size of the particles that may be contained in the fluid. Furthermore, in the microfluidic chip, the micropillars may or may not be bonded to the second resin substrate.

[0037] Examples of the shape of the cross-section of the micropillar (the plane perpendicular to the direction extending from the bottom of the flow channel toward the second resin substrate) include round, square, hexagonal, and flattened shapes. In this case, if the cross-sectional shape of the micropillar is circular, the outermost diameter of the cross-section is, for example, 10 μm or more and less than 100 μm. Furthermore, if the cross-sectional shape of the micropillar is flattened, the length in the short-side direction of the cross-section (usually the width direction of the flow channel) is, for example, 10 μm or more and less than 100 μm, and the length in the long-side direction of the cross-section (usually the direction in which the fluid flows) is, for example, 100 μm or more and 1000 μm or less.

[0038] The flow channels on the first resin substrate can be formed using, for example, microfabrication techniques such as photolithography and thermal imprinting, cutting, injection molding, etc.

[0039] The surface condition of the non-flow channel portion of surface A is not particularly limited, but it is preferably substantially flat in order to improve the leak resistance of the microfluidic chip. In this specification, "approximately flat" refers not only to a perfectly flat surface, but preferably to a surface with an arithmetic mean surface roughness Ra of 100 nm or less. The arithmetic mean surface roughness Ra is determined based on JIS B0633, for example, using Tokyo Seimitsu's "SURFCOM NEX231 SD2-13" It can be measured by methods such as "".

[0040] The first resin substrate is not particularly limited, and any substrate made of any resin can be used, for example, cyclic olefin resin (cycloolefin polymer), polycarbonate resin, aromatic polyetherketone resin, (meth)acrylic resin, vinyl alicyclic hydrocarbon resin, aromatic vinyl resin, etc. In particular, it is preferable to use a substrate made of cyclic olefin resin as the resin constituting the first resin substrate because it can be made into a microfluidic chip with excellent durability, as it exhibits less decrease in bonding strength over time due to moisture absorption and less decrease in optical stability due to heat. Furthermore, since substrates made of cyclic olefin resin have excellent moisture resistance and heat resistance, they can be suitably used in fields that require processing under high temperature and high humidity, such as autoclave sterilization. Furthermore, as monomers that can form cyclic olefin resins, norbornene monomers are preferred. Norbornene monomers are monomers containing a norbornene ring. Examples of norbornene monomers include bicyclic monomers such as bicyclo[2.2.1]hept-2-ene (common name: norbornene), 5-ethylidene-bicyclo[2.2.1]hept-2-ene (common name: ethylidenenorbornene), and their derivatives (those having substituents on the ring); tricyclo[5.2.1.0 2,6 Deca-3,8-diene (common name: dicyclopentadiene), and its derivatives, etc., as tricyclic monomers; tetracyclo[7.4.0.0 2,7 .1 10,13 ] Tetradeca-2,4,6,11-tetraene (common name: methanotetrahydrofluorene), tetracyclo[6.2.1.1 3,6 .0 2,7 ] Dodeca-4-ene (common name: tetracyclododecene), 9-ethylidenetetracyclo[6.2.1.1 3,6 .0 2,7 Examples include tetracyclic monomers such as dodeca-4-ene and their derivatives; these monomers may have substituents at arbitrary positions. The cyclic olefin resin may be an addition polymer, a ring-opening polymer, or a hydride thereof, but a ring-opening polymer or a hydride of a ring-opening polymer is preferred. In this specification, "(meth)acrylic" means acrylic and / or methacrylic.

[0041] In one embodiment of the present invention, it is preferable to use a resin with a light transmittance of 90% or more at 940 nm as the resin constituting the first resin substrate, in order to improve the productivity of the microfluidic chip. For example, the above-mentioned cyclic olefin resin can be used as such a resin. In this specification, the transmittance of a resin can be calculated by first preparing a 3 mm thick sample using the resin, measuring the absorbance of the sample, and using the obtained absorbance. For measuring the absorbance, an instrument such as the V-770 UV-Vis-Near-Infrared Spectrophotometer manufactured by JASCO Corporation can be used.

[0042] The first resin substrate may optionally contain additives other than the resin described above, such as light absorbers. However, from the viewpoint of preventing fluid contamination and maintaining the productivity, transparency, and moisture resistance of the microfluidic chip, the content of additives in the first resin substrate is preferably 10% by mass or less, more preferably 5% by mass or less, and particularly preferably 0% by mass. In other words, it is particularly preferable that the first resin substrate does not contain any additives.

[0043] <Second resin substrate> The second resin substrate has a B surface opposite to the A surface, and the B surface covers the flow channel portion of the first resin substrate. In other words, the second resin substrate can function as a cover substrate for a microfluidic chip. The second resin substrate may typically have through holes that serve as injection ports for fluids such as samples into the flow channel of the first resin substrate. Furthermore, as the second resin substrate, a substrate in which fine channels are formed on the side opposite to side B may be used.

[0044] The formation of through-holes in the second resin substrate can be carried out using, for example, microfabrication techniques such as photolithography and thermal imprinting, cutting, injection molding, etc.

[0045] The surface state of the B side (excluding the through-hole portion when the second resin substrate has through-holes) is not particularly limited, but is preferably substantially flat because it can improve the leak resistance of the microchannel chip.

[0046] The second resin substrate is not particularly limited, and for example, a substrate made of any resin such as a cyclic olefin resin (cycloolefin polymer), a polycarbonate resin, an aromatic polyether ketone resin, a (meth)acrylic resin, a vinyl alicyclic hydrocarbon resin, an aromatic vinyl resin, etc. can be used. Among them, since it can be made into a microchannel chip with less decrease in bonding strength over time due to moisture absorption and less decrease in optical stability due to heat, and excellent durability, as the resin constituting the second resin substrate, it is preferable to use a substrate made of a cyclic olefin resin. In addition, since the substrate made of a cyclic olefin resin is excellent in moisture resistance and heat resistance, it can be suitably used in fields where processing under high temperature and high humidity such as autoclave sterilization is required. Note that the monomers that can form a cyclic olefin resin preferably include norbornene-based monomers. Norbornene-based monomers are monomers containing a norbornene ring. Examples of norbornene-based monomers include bicyclo[2.2.1]hept-2-ene (common name: norbornene), 5-ethylidene-bicyclo[2.2.1]hept-2-ene (common name: ethylidene norbornene), and their derivatives (those having substituents on the ring), etc., which are bicyclic monomers; tricyclo[5.2.1.0 2,6 dec-3,8-diene (common name: dicyclopentadiene), and their derivatives, etc., which are tricyclic monomers; tetracyclo[7.4.0.0 2,7 .1 10,13 tetradeca-2,4,6,11-tetraene (common name: methanotetrahydrofluorene), tetracyclo[6.2.1.1 3,6 .0 2,7 dodeca-4-ene (common name: tetracyclododecene), 9-ethylidene tetracyclo[6.2.1.1 3,6 .0 2,7Examples include tetracyclic monomers such as dodeca-4-ene and their derivatives; these monomers may have substituents at arbitrary positions. The cyclic olefin resin may be an addition polymer, a ring-opening polymer, or a hydride thereof, but a ring-opening polymer or a hydride of a ring-opening polymer is preferred. Furthermore, from the viewpoint of ensuring good bonding between the channel substrate and the lid substrate, it is preferable that the channel substrate and the lid substrate be made of the same resin.

[0047] In one embodiment of the present invention, it is preferable to use a resin with a light transmittance of 90% or more at 940 nm as the resin constituting the second resin substrate, in order to improve the productivity of the microfluidic chip. For example, the cyclic olefin resin described above can be used as such a resin.

[0048] The second resin substrate may optionally contain additives such as light absorbers in addition to the resin described above. However, from the viewpoint of preventing fluid contamination and maintaining the productivity, transparency, and moisture resistance of the microfluidic chip, the content of additives in the second resin substrate is preferably 10% by mass or less, more preferably 5% by mass or less, and particularly preferably 0% by mass. In other words, it is particularly preferable that the second resin substrate does not contain any additives.

[0049] (Manufacturing method for microfluidic chips) The method for manufacturing a microfluidic chip of the present invention (hereinafter sometimes simply referred to as the "manufacturing method") is the method for manufacturing a microfluidic chip of the present invention as described above, and includes a bonding step of forming a bonding portion of the microfluidic chip using laser light. Using the above-described method for manufacturing microfluidic chips, it is possible to obtain microfluidic chips in which fluid contamination and clogging of the channels are suppressed. Furthermore, the manufacturing method of the present invention may optionally include other steps, such as a laminate manufacturing step, before the bonding step, in which a second resin substrate is placed on top of the A surface of the first resin substrate so that the B surface faces the A surface to obtain a laminate.

[0050] <Joining process> In the bonding process, a laser beam is used to form the joint of the microfluidic chip. Specifically, in the bonding process, a laser beam is used to directly bond surfaces A and B at a predetermined distance from the channel, along the channel, thereby forming the joint. By going through the bonding process, the desired microfluidic chip can be obtained.

[0051] The wavelength of the laser light is preferably 1.8 μm or more, more preferably 2.0 μm or more, preferably 40.0 μm or less, and more preferably 30.0 μm or less. If the wavelength of the laser light is within the above range, the appearance of the resulting microfluidic chip can be maintained in good condition.

[0052] The spot diameter of the laser beam is preferably 0.1 mm or larger, more preferably 0.5 mm or larger, preferably 8.0 mm or smaller, more preferably 4.0 mm or smaller, and even more preferably 1.5 mm or smaller. If the spot diameter of the laser beam is above the lower limit mentioned above, the pressure resistance of the resulting microfluidic chip can be effectively improved. On the other hand, if the spot diameter of the laser beam is below the above upper limit, clogging of the resulting microfluidic chip can be effectively suppressed. Furthermore, since clogging of the channels in the resulting microfluidic chip can be effectively suppressed, the leak resistance and pressure resistance of the microfluidic chip can be effectively improved.

[0053] The laser scanning speed can be adjusted as appropriate depending on the wavelength and spot diameter of the laser light, but for example, it can be 1 mm / sec or more, and may also be 5 mm / sec, or for example, 50 mm / sec or less, and may also be 20 mm / sec. [Examples]

[0054] The present invention will be described in detail below based on examples, but the present invention is not limited to these examples. The performance of the microfluidic chips in the examples and comparative examples was evaluated using the following methods, respectively.

[0055] <Dissolution of components> Water and 50% by mass ethanol were respectively filled into the channel sections of microfluidic chips and left at 40°C for 24 hours. Then, the amount of eluted components in the water and 50% by mass ethanol after standing was measured using GC / MS (Shimadzu Corporation, GCMS-QP2020) and LC / MS (LC system: Thermo Fisher Scientific, Ultimate 3000; mass spectrometer: Thermo Fisher Scientific, Orbitrap Fusion), and the elution of components was evaluated according to the following criteria. A: The amount of eluted component is 0 ppm (below the detection limit). B: Amount of eluted component is greater than 0 ppm

[0056] <blockage> The flow channels of the microfluidic chips obtained in the examples and comparative examples were examined, and the blockage of the flow channels was evaluated according to the following criteria. A: There are no narrow sections or foreign objects in the flow path. B: There is a narrow section or a foreign object in the flow path. C: There are two or more narrow sections or foreign objects in the flow path. D: The flow path is blocked, and the liquid cannot flow.

[0057] <Leak resistance> The leakage resistance of the microfluidic chips obtained in the examples and comparative examples was evaluated by flowing liquid through the fluid channels according to the following criteria. In Comparative Example 3, the fluid channel was blocked and no liquid flowed, so leakage resistance was not evaluated. A: There is no liquid seepage from the edges of the flow channel. B: Liquid seepage from the edge of the flow channel is 1 mm or less. C: Liquid seepage from the edge of the flow channel exceeds 1 mm. D: Liquid seeps from the edge of the channel section and leaks out of the microfluidic chip.

[0058] <Exterior condition> The microfluidic chips obtained in the examples and comparative examples were visually inspected for any clouding or surface deformation at the joints, and their appearance was evaluated according to the following criteria. A: There is no clouding or surface deformation at the joint. B: The joint is slightly cloudy. C: The joint is cloudy and the surface is slightly uneven. D: The joint is whitened and the surface is uneven.

[0059] <Pressure resistance> A liquid delivery pump was connected to one of the through-holes in the lid substrate of the microfluidic chip obtained in the examples and comparative examples using a tube, and deionized water with a coloring agent added was flowed through the flow channel pattern. Next, after confirming that liquid was coming out of the other through-hole in the lid substrate, this through-hole was sealed with a rubber stopper, and the liquid delivery pressure was started at 100 kPa (gauge pressure) and held for 3 minutes. After 3 minutes, if there was no leakage around the flow channel, the liquid delivery pressure was increased by another 100 kPa and held for 3 minutes in the same manner. The increase and holding of the liquid delivery pressure was repeated, and leakage was checked until the liquid delivery pressure reached 500 kPa, and the pressure resistance was evaluated according to the following criteria. A: No liquid leaks even at a liquid delivery pressure of 500kPa. B: The liquid leaked before the pumping pressure reached 500kPa.

[0060] (Example 1) <Laminate manufacturing process> First, as the first resin substrate, a channel substrate (thickness: 1 mm, outer dimensions: 76 mm × 26 mm) was prepared using cycloolefin polymer (manufactured by Zeon Corporation, ZEONEX® 690R, glass transition temperature: 136°C, light transmittance at a wavelength of 0.940 μm: 90.6%) as the raw material. A channel pattern (channel section and end) was formed on one side (side A) of the channel substrate, and the surface condition of the non-channel section was approximately flat. Next, a lid substrate with through holes and made of the same material and dimensions as the flow channel substrate was prepared as a second resin substrate. The lid substrate was then placed on top of surface A of the flow channel substrate to obtain a laminate (the surface of the lid substrate opposite surface A of the flow channel substrate corresponds to surface B). The position of the through holes in the lid substrate was set to correspond to the edges of the flow channel substrate. Furthermore, the surface of surface B, excluding the through-hole area, is substantially flat.

[0061] <Joining process> The laminate was placed on the stage of a semiconductor laser welding machine (manufactured by Seidensha Electronics Industry Co., Ltd.), and then a 10 mm thick glass plate was placed on top of the laminate to fix it in place. Then, using a laser beam wavelength of 2.0 μm, a laser spot diameter of 0.5 mm, an output of 30 W, and a laser scanning speed of 20 mm / sec, the laminate was fused in an annular shape along the flow channel pattern (flow channel section and end section) at a position 200 μm away from the flow channel pattern, joining sides A and B to obtain the desired microfluidic chip. The obtained microfluidic chips were used to evaluate component elution, clogging, leak resistance, appearance, and pressure resistance. The results are shown in Table 1.

[0062] (Example 2) In the bonding process, the bonding conditions were changed to a laser wavelength of 10.0 μm, a laser spot diameter of 1.0 mm, an output of 30 W, and a laser scanning speed of 10 mm / sec. Except for these changes, the various operations and evaluations were carried out in the same manner as in Example 1. The results are shown in Table 1.

[0063] (Example 3) In the bonding process, various operations and evaluations were carried out in the same manner as in Example 1, except that the bonding conditions were changed to a laser wavelength of 25.0 μm, a laser spot diameter of 3.0 mm, an output of 30 W, and a laser scanning speed of 5 mm / sec. The results are shown in Table 1.

[0064] (Example 4) In the bonding process, the bonding conditions were changed to a laser wavelength of 50.0 μm, a laser spot diameter of 1.0 mm, an output of 30 W, and a laser scanning speed of 10 mm / sec. Except for these changes, the various operations and evaluations were carried out in the same manner as in Example 1. The results are shown in Table 1.

[0065] (Example 5) In the bonding process, the bonding conditions were changed to a laser wavelength of 10.0 μm, a laser spot diameter of 10.0 mm, an output of 30 W, and a laser scanning speed of 10 mm / sec. Except for these changes, the various operations and evaluations were carried out in the same manner as in Example 1. The results are shown in Table 1.

[0066] (Example 6) In the bonding process, various operations and evaluations were carried out in the same manner as in Example 1, except that the bonding conditions were changed to a laser wavelength of 10.0 μm, a laser spot diameter of 1.0 mm, an output of 30 W, and a laser scanning speed of 5 mm / sec. The results are shown in Table 1.

[0067] (Example 7) In the joining process, the A and B sides of the flow channel substrate were joined such that the ratio of the planar area of ​​the joint to the planar area of ​​the non-flow channel side A was 1.3%. Except for this, various operations and evaluations were carried out in the same manner as in Example 1. The results are shown in Table 1.

[0068] (Example 8) In the joining process, the A and B surfaces were joined so that the shortest width of the channel separation was 500 μm. Except for this, various operations and evaluations were carried out in the same manner as in Example 1. The results are shown in Table 1.

[0069] (Comparative Example 1) <Laminate manufacturing process> First, as the first resin substrate, a channel substrate (thickness: 1 mm, outer dimensions: 76 mm × 26 mm) was prepared using cycloolefin polymer (manufactured by Zeon Corporation, ZEONEX® 690R, glass transition temperature: 136°C, light transmittance at a wavelength of 0.940 μm: 90.6%) as the raw material. A channel pattern (channel section and end) was formed on one side (side A) of the channel substrate, and the surface condition of the non-channel section was approximately flat. Next, a lid substrate with through holes and made of the same material and dimensions as the channel substrate was prepared as a second resin substrate. UV adhesive (Henkel Japan LOCTITE AA3105) was applied to the side (B side) facing side A of the channel substrate using a wire bar #2. The channel substrate and the lid substrate were then stacked so that the side with the UV adhesive applied faced side A of the channel substrate, thereby obtaining a laminate. The position of the through holes in the lid substrate was positioned to correspond to the edge of the channel substrate. The surface of side B, excluding the through holes, was approximately flat.

[0070] <Joining process> Next, the laminate obtained above is subjected to ultraviolet irradiation at 3600 mJ / cm² using an ultraviolet irradiation device. 2 By irradiating with 360nm ultraviolet light, the UV adhesive was cured to bond side A and side B, thereby obtaining a microfluidic chip. The obtained microfluidic chips were used to evaluate component elution, clogging, leak resistance, appearance, and pressure resistance. The results are shown in Table 1.

[0071] (Comparative Example 2) Except for joining surfaces A and B in the joining process so that the shortest width of the channel separation was 0 μm, various operations and evaluations were carried out in the same manner as in Example 1. The results are shown in Table 1.

[0072] In Table 1, "Joint area" refers to the planar area of ​​the joint formed along the flow channel. "Non-flow area" refers to the planar area of ​​the non-flow portion. "Area of ​​channel separation" refers to the area of ​​the channel separation in a plan view.

[0073] [Table 1]

[0074] As is clear from Table 1, the microfluidic chips in the examples demonstrate suppressed fluid contamination and clogging of the flow channels. [Industrial applicability]

[0075] According to the present invention, it is possible to provide a microfluidic chip in which fluid contamination and clogging of the flow path are suppressed. Furthermore, the present invention provides a method for manufacturing the above-described microfluidic chip. [Explanation of symbols]

[0076] 10 Microfluidic Chips 11. First resin substrate 111 Side A 12. Second resin substrate 121 B side 13 Through hole 14 Flow channel section 141 First flow channel 142 Second flow channel 143 Third flow channel 144 Fourth channel section 15 Joint 151 First joint 152 Second joint 153 Third joint 154 Fourth joint 16. Channel separation section 161 First channel separation section 162 Second channel separation section 163 Third channel separation section 164 Fourth channel separation section 17 End 171 First end 172 Second end 173 Third end 174 The fourth end 18 End separation 181 First end separation 182 Second end separation 183 Third end separation 184 Fourth end separation

Claims

1. A microfluidic chip comprising a first resin substrate and a second resin substrate, The first resin substrate has a surface A, and a flow channel is provided on surface A. The second resin substrate has a B surface facing the A surface, and the B surface covers the flow channel portion. Surface A and surface B are directly joined by a joint formed along the flow path portion. The flow channel portion and the joint portion are separated by a flow channel separation portion provided in the plane direction of surface A. A microfluidic chip in which the channel separation portion and the B surface are in contact or in close proximity.

2. The microfluidic chip according to claim 1, wherein the first resin substrate and the second resin substrate are made of a cyclic olefin resin.

3. The microfluidic chip according to claim 1, wherein the shortest width of the joint formed along the flow channel is 0.1 mm or more and 8.0 mm or less.

4. The microfluidic chip according to claim 1, wherein the ratio of the planar area of ​​the joint formed along the flow channel to the planar area of ​​the flow channel separation portion is 200% or more.

5. The microfluidic chip according to claim 1, wherein the shortest width of the channel separation portion is 100 μm or more and 400 μm or less.

6. A method for manufacturing a microfluidic chip according to any one of claims 1 to 5, A method for manufacturing a microfluidic chip, including a bonding step of forming the bonding portion using laser light.

7. The method for manufacturing a microfluidic chip according to claim 6, wherein the wavelength of the laser light is 1.8 μm or more and 40.0 μm or less.

8. The method for manufacturing a microfluidic chip according to claim 6, wherein the spot diameter of the laser beam is 0.1 mm or more and 8.0 mm or less.

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