Manufacturing method of microfluidic chip

Abstract

To provide a micro flow channel chip which causes less air bubbles and has less residual air bubbles during liquid feeding to a flow channel groove and storage after the liquid feeding, and a method for manufacturing the same.SOLUTION: A micro flow channel chip comprises: a resin substrate having a flow channel groove formed on at least one surface; and a resin film having a base material layer and an adhesive layer and joined to the resin substrate via the adhesive layer so as to cover the flow channel groove. When a square of surface roughness (Rz) of a joined surface where the resin substrate and the adhesive layer of the resin film are joined to each other is represented by X(μm2), and the total area of film lifting of the resin film per 100 μm2 of a joined surface is represented by Y (μm2), X and y satisfy all of the following relational expressions (1) to (3) of Y≤0.64X-12.2 (1), X≥23.0 (2) and Y≤20.0 (3).SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a microchannel chip for use in the pharmaceutical industry and the like, and a method for producing the same. [Background technology]

[0002] In fields such as the pharmaceutical industry, which is involved in the manufacture of medicines and reagents, microchannel chips are sometimes used for the analysis, synthesis, screening, etc. of nucleic acids, proteins, sugar chains, etc. These microchannel chips have minute flow channels (also called microchannels) formed in a substrate made of resin or the like using microfabrication technology, and within the minute space containing the microchannels, chemical reactions, separation, detection, analysis, etc. of samples can be carried out (for example, Patent Document 1, etc.).

[0003] Many microchannel chips used for such analyses include a substrate (resin substrate) made of resin and having a microchannel formed on its surface, and a resin film bonded to the resin substrate. The resin substrate and the resin film are bonded mainly by thermal fusion or by adhesion using an adhesive layer provided on the resin film. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2014-206512 A Summary of the Invention [Problem to be solved by the invention]

[0005] However, when a resin substrate and a resin film are bonded by adhesion with an adhesive layer (lamination via an adhesive layer), there are likely to be areas on the bonding surface where the adhesive layer does not sufficiently conform to the resin substrate (areas with low conformity), meaning that the film is likely to float slightly on the bonding surface, and there is a problem that gas can enter the flow channel from this slightly floating area during or after liquid transfer to the flow channel, generating and remaining air bubbles that can hinder liquid transfer, chemical reactions, separation, detection, etc. In particular, as the surface roughness (Rz) of the bonding surface of the microfluidic chip increases, there is a tendency for this slightly floating film to cause air bubbles to be generated and remain in the flow channel.

[0006] The present invention has been made in consideration of the above-mentioned problems, and aims to provide a microchannel chip that reduces the generation and residual air bubbles when liquid is delivered to a channel and during storage after liquid delivery, and a method for manufacturing the same. [Means for solving the problem]

[0007] The microchannel chip according to the present invention comprises a resin substrate having a flow channel formed on at least one surface thereof, and a resin film having a base layer and an adhesive layer and bonded to the resin substrate by the adhesive layer so as to cover the flow channel, and the square of the surface roughness (Rz) of the bonding surface where the resin substrate and the adhesive layer of the resin film are bonded is defined as X (μm 2 ), bonding surface 100μm 2 The total floating area of ​​the resin film per unit area is expressed as Y (μm 2 ) the present invention is characterized in that it satisfies all of the following relational expressions (1) to (3). (1) Y≦0.64X-12.2 (2) X≧23.0 (3) Y≦20.0 Effect of the Invention

[0008] According to the present invention, a microchannel chip can be obtained in which the adhesive layer of the resin film has high conformability to the resin substrate at the bonding surface, and in which there is little generation of air bubbles or residual air bubbles during liquid delivery to the flow channel and during storage after liquid delivery. [Brief description of the drawings]

[0009] [Figure 1] FIG. 2 is an enlarged cross-sectional view showing the vicinity of a flow channel of the micro-flow channel chip according to the present embodiment. [Diagram 2] FIG. 2 is a front view of the micro-channel chip according to the present embodiment. [Diagram 3] 3A to 3C are enlarged cross-sectional views of the resin film or the micro-channel chip in a peeling step (I), a pre-bonding heating step (II), and a bonding step (III) in the manufacturing method of the micro-channel chip according to the present embodiment. [Figure 4] 13 is an enlarged cross-sectional view of a resin film in a modified example of a pre-bonding heating step in the manufacturing method of the micro-channel chip according to the embodiment. FIG. [Diagram 5] 1 is a graph showing the relationship between the square (X: μm2) of the surface roughness (Rz) of the bonding surface of the micro-channel chip and the total film floating area (Y: μm2) of the resin film per 100 μm2 of this bonding surface. [Figure 6] 1 shows images (drawing substitute photographs) taken with a laser microscope of the bonding surfaces of the microchannel chips of Samples 1 and 2 shown in the Examples. (a) is an image of the bonding surface of Sample 1, and (b) is an image of the bonding surface of Sample 2. [Figure 7] 1 shows images (drawing substitute photographs) taken by a laser microscope of the bonding surfaces of the micro-channel chips of Samples 3 and 4 shown in the Examples. (c) is an image of the bonding surface of Sample 3, and (d) is an image of the bonding surface of Sample 4. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of a micro-channel chip and a method for producing the same according to the present invention will be described with reference to the drawings. The embodiment described below is merely an example for facilitating understanding of the present invention, and is not intended to limit the present invention. In other words, the shapes, dimensions, arrangements, and other aspects of the components described below may be modified or improved without departing from the spirit of the present invention, and the present invention naturally includes equivalents thereof. In addition, in all drawings, similar components are given the same reference numerals, and duplicate explanations are omitted as appropriate. Note that in all drawings, some parts are not given reference numerals (omitted) for convenience. Furthermore, the dimensional ratios of each member shown in the drawings may differ from the actual dimensional ratios in order to facilitate understanding of the invention.

[0011] <Summary> First, an overview of the micro-channel chip according to this embodiment will be described with reference to Figs. 1, 2, 5, etc. Fig. 1 is a schematic enlarged cross-sectional view of the vicinity of flow channel 11 of micro-channel chip 100 according to this embodiment. Fig. 2 is a front view of micro-channel chip 100 according to this embodiment. Furthermore, Fig. 5 is a graph showing the square of the surface roughness (Rz) (X: μm 2 ) and 100μm of the joint surface 30 2 The total film floating area of ​​the resin film 20 per 2 ) is a graph showing the relationship between

[0012] 1 and 2, the micro-channel chip 100 according to this embodiment includes a resin substrate 10 having a channel groove 11 formed on at least one surface thereof, and a resin film 20 having a base layer 21 and an adhesive layer 23 and bonded to the resin substrate 10 by the adhesive layer 23 so as to cover the channel groove 11. The square of the surface roughness (maximum height roughness: Rz) of a bonding surface 30 where the resin substrate 10 and the adhesive layer 23 of the resin film 20 are bonded is defined as X (μm 2 ), 100μm of the joint surface 30 2 The total film floating area of ​​the resin film 20 per unit area is expressed as Y (μm 2), the micro-channel chip 100 satisfies all of the following relations: Y≦0.64X-12.2, X≧23.0, and Y≦20.0. This is because, as shown in the data of the examples (FIG. 5, etc.) described later, when the surface roughness (Rz) of the bonding surface 30 of the micro-channel chip 100 is a certain level or more, the resin film 20 before bonding is heated under a predetermined condition and then bonded to the resin substrate 10, the total area of ​​the film floating on the bonding surface 30 can be made to be a certain level or less in relation to the square of the surface roughness (Rz) of the bonding surface 30, and the generation or remaining of air bubbles in the flow channel 11 is less likely to occur. Therefore, the micro-channel chip 100 according to this embodiment can be obtained by the manufacturing method of the micro-channel chip 100 according to this embodiment, which includes a pre-bonding heating step described later. Note that these numerical values ​​are significant figures up to the indicated digits (the same applies below). Here, the "film floating" in the micro-channel chip 100 of this embodiment refers to a portion (micro-floating of the film) in which the adhesive layer 23 of the resin film 20 does not sufficiently follow the surface of the resin substrate 10 to be bonded on the bonding surface 30 and floats slightly away from the surface (micro-floating of the film). Note that in Fig. 1 and the like, the film floating on the bonding surface 30 may not be clearly shown.

[0013] The microchannel chip 100 according to this embodiment may have a configuration in which one resin substrate 10 and one resin film 20 are bonded together as shown in FIGS. 1 and 2, but may also have a configuration in which flow channel 11 is formed on both sides of the resin substrate 10 and a resin film 20 is bonded to each of these sides, or a configuration in which an adhesive layer 23 is provided on each of both surfaces of the base material layer 21 of the resin film 20 and the surfaces of the resin substrate 10 on which the flow channel 11 is formed are bonded to each of these adhesive layers 23.

[0014] Furthermore, in the micro-channel chip 100 according to this embodiment, one or more ports 13 that can serve as an inlet or outlet for a sample or a degassing port, for example, as shown in Fig. 2, may be formed on at least one surface of the resin substrate 10. The port 13 may be cylindrical as shown in Fig. 2, or may have another shape such as a square tube, and may even be formed penetrating the resin substrate 10.

[0015] Furthermore, the overall shape (external shape) of the microchannel chip 100 according to this embodiment is preferably a square plate shape from the standpoint of ease of use in equipment, etc., and ease of handling, but it may also be a circular plate shape, and is not particularly limited as long as it is a plate shape.

[0016] As described above, the micro-channel chip 100 according to this embodiment has a surface roughness (Rz) of the bonding surface 30 squared (X: μm 2 ) and 100μm of the joint surface 30 2 The total film floating area of ​​the resin film 20 per 2 ) satisfy the relational formula (1) Y≦0.64X−12.2, the relational formula (2) X≧23.0, and the relational formula (3) Y≦20.0 (the ratio of the total film floating area at the bonding surface 30 is 20.0% or less) (FIG. 5, etc.). In the case of the above-mentioned configuration in which the resin film 20 is bonded to both sides of the resin substrate 10, or the configuration in which the resin substrate 10 is bonded to both surfaces of the resin film 20, it is sufficient that X and Y at least at any of the bonding surfaces 30 satisfy all of the relational formulas (1) to (3), and more preferably, X and Y at any of the bonding surfaces 30 satisfy all of the relational formulas (1) to (3).

[0017] Regarding the above relational expression (1), this has been derived based on the data of the examples described later (FIG. 5, etc.), but in the micro-channel chip 100 according to this embodiment, it may further satisfy Y≦0.64X−12.5 (relational expression (4)), or may further satisfy Y≦0.64X−12.8 (relational expression (5)).

[0018] In addition, with respect to the above relational expression (2), the lower limit of X is more preferably 25.0 or more (X≧25.0, Rz is 5 μm or more), more preferably 30.25 or more (X≧30.25, Rz is 5.5 μm or more), more preferably 31.6 or more (X≧31.6), more preferably 33.0 or more (X≧33.0), and even more preferably 34.3 or more (X≧34.3). This is because, in the manufacture of the micro-channel chip 100 according to this embodiment, the effect of the pre-bonding heating step (heating of the resin film 20 before bonding under predetermined conditions) described later is more likely to be exhibited. In addition, the lower limit of X may be 35.0 or more (X≧35.0), or may be 36.0 or more (X≧36.0, Rz is 6 μm or more).

[0019] The upper limit of X is more preferably less than 64.0 (X<64.0, Rz is less than 8 μm), and even more preferably 56.25 or less (X≦56.25, Rz is 7.5 μm or less). This is because it is easier to adjust the conditions of the pre-bonding heating step described below in the manufacture of micro-channel chip 100 of this embodiment. However, even if X is larger, by adjusting the conditions of the pre-bonding heating step described below (for example, by setting the heating temperature and / or heating time close to the upper limit within a predetermined range), micro-channel chip 100 of this embodiment that also satisfies the above relational expressions (1) and (3) can be manufactured. Moreover, the upper limit of X is more preferably 52.0 or less (X≦52.0), more preferably 51.4 or less (X≦51.4), more preferably 50.3 or less (X≦50.3), more preferably 49.0 or less (X≦49.0, Rz is 7 μm or less), more preferably 48.7 or less (X≦48.7), more preferably 45.6 or less (X≦45.6), and more preferably 42.5 or less (X≦42.5). This is because the value of Y is easily smaller (for example, less than 19.0, further less than 17.0, and further less than 15.0) in the micro-channel chip 100.

[0020] Since the number and pattern of flow grooves in a micro-channel chip must be designed according to the purpose, the surface roughness (Rz) of the bonding surface between the resin substrate and the adhesive layer of the resin film may exceed a certain level due to problems in processing and difficulty in polishing. In such a case, there is a possibility that a lot of film lifting occurs on this bonding surface, but in the micro-channel chip 100 according to the present embodiment, even if the surface roughness (Rz) of the bonding surface 30 is relatively large, the resin film 20 is heated under predetermined conditions in the pre-bonding heating step described below, and then bonded. Therefore, X and Y satisfy all of the above-mentioned relational expressions (1) to (3), and the bonding surface 30 (particularly the bonding surface 30 near the flow groove 11) has a very small amount of film lifting. In the micro-channel chip 100 of this embodiment having such a configuration, when liquid is delivered to the flow channel 11 or when the micro-channel chip 100 is stored after this liquid delivery (e.g., when stored at room temperature (25°C)), there is extremely little gas intrusion into the flow channel 11 from the bonding surface 30, and there is extremely little generation or residual air bubbles in the flow channel 11.

[0021] Here, in the present invention, "surface roughness (Rz)" means the maximum height roughness defined in JIS B 0601 (2013). In other words, a reference length is extracted from the roughness curve of a surface (such as the joining surface 30 in the present invention) in the direction of the average line, and the sum of the maximum peak height Zp and maximum valley depth Zv of the roughness curve in this extracted portion is expressed in μm. The surface roughness (Rz) is measured by using a non-contact measuring device (such as a laser microscope VK-9710 manufactured by Keyence Corporation) on the measurement surface (such as the bonding surface 30 in the present invention).

[0022] <Resin substrate> Next, the resin substrate 10 of the micro-channel chip 100 according to this embodiment will be described in detail.

[0023] The resin substrate 10 of the microchannel chip 100 according to this embodiment is a plate-like substrate made of resin with a channel groove 11 formed on at least one surface thereof, and its size, for example, if rectangular, is approximately 10 mm to 100 mm x 10 mm to 200 mm, with a thickness of 0.5 mm to 3.0 mm.

[0024] Furthermore, the flow channel 11 formed in the resin substrate 10 is a fine groove, and it is sufficient that it has an opening width and depth that allow the passage of a liquid sample, and for example, the opening width (opening length in the short direction of the flow channel 11: the length of the part indicated by W in the embodiment of Figs. 1 and 2) is 1 mm or less, preferably 20 µm to 500 µm, and the depth is 10 µm to 500 µm, preferably 20 µm to 100 µm. The flow channel 11 can be formed by using a mold that can also form the flow channel 11 when molding the resin substrate 10 by resin injection molding, or by micro-machining the molded resin substrate 10 (cutting or adding members).

[0025] Furthermore, the shape of the flow channel 11 is not particularly limited, and may be rectangular, polygonal, semicircular, or the like in cross section, but is preferably trapezoidal or semicircular in cross section because this facilitates stable liquid transfer. The number of flow channel 11 formed in the resin substrate 10 is also not limited to one, and multiple flow channel 11 may be formed in series or parallel. The flow channel 11 may branch or intersect, and may be appropriately designed according to the above-mentioned cross-sectional shape, number, opening width, depth, and the like, depending on the intended use.

[0026] Here, the depth of the flow channel 11 formed in the resin substrate 10 of the micro-channel chip 100 according to this embodiment is the length of the flow channel 11 in the thickness direction of the resin substrate 10. In other words, in the flow channel 11 formed in the resin substrate 10, when a perpendicular line (a line parallel to the thickness direction of the resin substrate 10) is drawn from the imaginary outer surface of the resin substrate 10 that existed before the flow channel 11 is formed, the depth is the longest distance among the distances between the points at which the perpendicular line intersects with the surface constituting the flow channel 11. For example, in the embodiment shown in FIG. 1, the depth of the flow channel 11 is the longest distance among the distances between two points at which the perpendicular line intersects with the line on the lower side of the flow channel 11 (the bottom surface constituting the flow channel 11, which has an inverted trapezoidal cross section) when a perpendicular line is drawn from the line on the upper side of the flow channel 11 formed in the resin substrate 10 before the resin film 20 is bonded (D in FIG. 1).

[0027] Furthermore, the surface of the flow channel 11 of the resin substrate 10 (the surface constituting the flow channel 11) may be subjected to a surface treatment such as hydrophilization treatment or surface treatment functional group formation treatment. For example, such a surface treatment is a treatment for introducing an oxygen-containing functional group. By introducing the oxygen-containing functional group, the hydrophilicity of the surface is improved, and the sample (water or a sample containing a hydrophilic solvent) can be passed more smoothly. Examples of the oxygen-containing functional group include a group of polar functional groups such as carbonyl groups such as aldehyde groups and ketone groups, carboxyl groups, hydroxyl groups, ether groups, peroxy groups, and epoxy groups. For example, a plasma treatment, a corona discharge treatment, an excimer laser treatment, and a flame treatment can be used as the introduction treatment. This surface treatment may also be performed on the surface of the part of the resin film 20 (the surface of the adhesive layer 23) covering the flow channel 11 described later.

[0028] The resin substrate 10 is made of a resin material. Here, being made of a resin material means that the resin material is the main material (the resin material is contained in the total mass of the resin substrate 10 at 60 mass% or more, more preferably at 70 mass% or more, even more preferably at 80 mass% or more, and even more preferably at 90 mass% or more). The resin substrate 10 may have a layer made of a material other than the resin material (e.g., glass, etc.) on a part of the surface side that is not joined to the resin film 20, for example, but it is preferable that the entire resin substrate 10 is made of a resin material (especially the same resin material). This is because the resin substrate 10 itself can be easily molded. The flow channel 11 may be formed on both surfaces of the resin substrate 10.

[0029] Examples of resin materials used to manufacture the resin substrate 10 include, but are not limited to, polyolefin resins such as polyethylene (PE), polypropylene (PP), and polymethylpentene (PMP), cyclic olefin resins such as cycloolefin polymer (COP) and cycloolefin copolymer (COC), polystyrene resins such as polystyrene (PS), polycarbonate resins such as polycarbonate (PC), polyacrylic resins such as polymethyl methacrylate (PMMA), and polyester resins such as polyethylene terephthalate (PET), polybutylene terephthalate (PBT), and polyethylene naphthalate (PEN). These may be used alone or in combination of two or more. The resin substrate 10 can be constructed using such resin materials as the main material.

[0030] In particular, because of the ease of bonding to the adhesive layer 23 of the resin film 20 described above and the ease of ensuring the transparency of the resin substrate 10, it is more preferable that the resin substrate 10 be made of any one selected from the group consisting of polystyrene-based resins, polycarbonate-based resins, polyacrylic-based resins, and cyclic olefin-based resins, and it is even more preferable that the resin substrate 10 be made of any one selected from the group consisting of polystyrene (PS), polycarbonate (PC), polymethyl methacrylate (PMMA), and cycloolefin copolymer (COC).

[0031] <Resin film> Next, resin film 20 of micro-channel chip 100 according to this embodiment will be described in detail.

[0032] The resin film 20 of the microchannel chip 100 according to this embodiment has a base material layer 21 that is the base material (basic material of the film) and an adhesive layer 23 that contains an adhesive component, and is configured by laminating the base material layer 21 and the adhesive layer 23. The adhesive layer 23 of the resin film 20 is bonded to the surface of the resin substrate 10 on which the flow channel 11 is formed. The base material layer 21 may be a single layer (single layer), or may be configured by laminating a plurality of layers that are base materials. The adhesive layer 23 is provided on at least one surface of the base material layer 21, but may be configured to have the adhesive layer 23 on both surfaces of the base material layer 21, or may be configured to have the adhesive layer 23 formed in a specific pattern (pattern coating) on ​​one surface of the base material layer 21. Furthermore, other layers (e.g., a coating layer or an adhesive layer (laminate adhesive layer)) may be included between the base material layer 21 and the adhesive layer 23, on the surface side of the base material layer 21 opposite to the surface side that is bonded to the resin substrate 10, or between layers of the base material layer 21 in which multiple base material layers are laminated.

[0033] The size of the resin film 20, if it is rectangular, is, for example, the same as that of the resin substrate 10 described above, that is, 10 mm to 100 mm × 10 mm to 200 mm. From the viewpoint of ease of bonding to the resin substrate 10, the lower limit of the total thickness of the resin film 20 is preferably 0.01 mm or more, more preferably 0.02 mm or more, and even more preferably 0.03 mm or more. The upper limit is preferably 1.0 mm or less, more preferably 0.5 mm or less, and even more preferably 0.2 mm or less, since this does not affect the conformability of the resin film 20 to the resin substrate 10 at the bonding surface 30. Here, the total thickness of the resin film 20 is determined by measuring the length between the main surfaces (between the front and back outer surfaces) of the resin film 20 at any ten points in the normal vector direction of the main surfaces of the resin film 20 and calculating the average.

[0034] The thickness of the base layer 21 of the resin film 20 is preferably at least 50 μm, more preferably at least 70 μm, even more preferably at least 80 μm, even more preferably more than 85 μm, even more preferably at least 90 μm, and even more preferably at least 100 μm. The upper limit is preferably at most 130 μm, and more preferably at most 125 μm. This is because the hardness of the resin film 20 is easily brought to a desired state by heating in the pre-bonding heating step described later, and the resin film 20 is easily bonded to the resin substrate 10. Here, the thickness of the base material layer 21 is determined by measuring the length between the main surfaces (between both surfaces) of the base material layer 21 at any 10 points in the normal vector direction of the main surfaces of the base material layer 21 and calculating the average. When the base material layer 21 is configured by laminating a plurality of layers that become base materials, the thickness of the base material layer 21 is the sum of the thicknesses of the laminated layers that become base materials calculated in the same manner as above.

[0035] Furthermore, the upper limit of the thickness of the adhesive layer 23 of the resin film 20 is preferably less than 20 μm, more preferably less than 15 μm, and even more preferably 10 μm or less. This is because the viscosity can be easily reduced by heating in the pre-bonding heating step described later, and the manufacturing cost can be further reduced by reducing the thickness of the adhesive layer 23. Furthermore, when the adhesive layer 23 is bonded to the resin substrate 10, the expansion of the adhesive layer 23 into the flow channel 11 is further suppressed, and the internal volume of the flow channel 11 is more easily secured (the flow channel 11 is more likely to have a more stable liquid delivery speed, etc.). From the viewpoint of maintaining the function of the adhesive layer 23, the lower limit of the thickness of the adhesive layer 23 is preferably 3 μm or more, and even more preferably 5 μm or more. Here, the thickness of the adhesive layer 23 is found by measuring the length between the main surfaces of the adhesive layer 23 (between both surfaces (one of which is the bonding surface 30)) at any ten locations in the normal vector direction of the main surface of the adhesive layer 23 bonded to one resin substrate 10, and calculating the average. Therefore, in the case of a resin film 20 in which the adhesive layer 23 is provided on both surfaces of the base layer 21, the thickness of the adhesive layer 23 is the thickness of the adhesive layer 23 on one surface (one side surface) bonded to the resin substrate 10, and is not the sum of the thicknesses of the adhesive layer 23 on both surfaces.

[0036] Examples of the resin material used for the base layer 21 of the resin film 20 include polyolefin resins such as polyethylene (PE), polypropylene (PP), and polymethylpentene (PMP), cyclic olefin resins such as cycloolefin polymer (COP) and cycloolefin copolymer (COC), polystyrene resins such as polystyrene (PS), polycarbonate resins such as polycarbonate (PC), polyacrylic resins such as polymethyl methacrylate (PMMA), and polyester resins such as polyethylene terephthalate (PET), polybutylene terephthalate (PBT), and polyethylene naphthalate (PEN). These may be used alone or in combination of two or more. In the case of using two or more in combination, two or more resin materials may be mixed and used, or two or more layers formed of a single resin material may be laminated and used. The base material layer 21 of the resin film 20 can be constructed using such a resin material as the main material (for example, so that it contains 60 mass % or more of the total mass of the base material layer 21, more preferably 70 mass % or more, even more preferably 80 mass % or more, and even more preferably 90 mass % or more).

[0037] In addition, since this makes it easier to achieve the effect of heating in the pre-bonding heating process described below and also makes it easier to ensure the transparency of the resin film 20, it is more preferable that the base material layer 21 of the resin film 20 is composed of (used as the main material for) any one selected from the group consisting of polystyrene-based resins, polycarbonate-based resins, polyacrylic-based resins, and cyclic olefin-based resins, and it is even more preferable that this base material layer 21 is composed of any one selected from the group consisting of polystyrene (PS), polycarbonate (PC), polymethyl methacrylate (PMMA), and cycloolefin copolymer (COC).

[0038] Furthermore, if the aforementioned resin substrate 10 and base layer 21 of this resin film 20 are made of the same resin material, and this resin material is any one selected from the group consisting of polystyrene (PS), polycarbonate (PC), polymethyl methacrylate (PMMA), and cycloolefin copolymer (COC), this is even more preferable from the standpoint of ensuring the transparency of the obtained microchannel chip 100 (ease of observation work, etc.).

[0039] The adhesive component used in the adhesive layer 23 of the resin film 20 may be, for example, one or more selected from polyacrylic resins such as acrylic esters (acrylic adhesives), silicone resins such as polydimethylsiloxane (silicone adhesives), and polyurethane resins such as polyurethane (urethane adhesives). The adhesive layer 23 of the resin film 20 may be formed using such an adhesive component as a main component (for example, so as to be contained in an amount of 60 mass % or more, more preferably 70 mass % or more, even more preferably 80 mass % or more, and even more preferably 90 mass % or more of the total mass of the adhesive layer 23).

[0040] It is very preferable that the adhesive component constituting the adhesive layer 23 is a polyacrylic resin (acrylic adhesive), since the heating effect in the pre-bonding heating step described below is more likely to be exhibited, and the properties of the acrylic adhesive make it easier for the resin film 20 to conform more closely to the surface of the resin substrate 10 on which the flow channel 11 is formed. In this case, it is even more preferable that the resin substrate 10 is also made of the same type of resin material, that is, a polyacrylic resin.

[0041] Furthermore, the resin film 20 of the micro-channel chip 100 according to this embodiment may further contain additives such as plasticizers, antioxidants, flame retardants, antistatic agents, pigments, dyes, etc., within the scope that does not impair the effects of the present invention. This also applies to the resin substrate 10 described above.

[0042] Furthermore, the resin film 20 may have electrode portions formed by metal deposition or a thin metal film, for example, so as to correspond to the flow channel 11 and the port 13 formed in the resin substrate 10.

[0043] In addition, the resin film 20 may have a release film 25 attached to its adhesive layer 23 before bonding to the resin substrate 10. The release film 25 is not particularly limited as long as it is a film that can be peeled off from the adhesive layer 23, but it is preferable that the release film 25 is made of a material (for example, a resin material (polyethylene terephthalate (PET) or the like) or a paper material) that does not affect the properties of the adhesive layer 23 of the resin film 20 when the release film 25 is peeled off, and has a strength and thickness that are not easily affected. In addition, the size of the release film 25 is not particularly limited as long as it is a size that can be attached to the adhesive layer 23 of the resin film 20, but it is more preferable that at least a part of the release film 25 protrudes from the outer shape of the resin film 20 when attached to the adhesive layer 23 of the resin film 20, or is larger than the size of the resin film 20 to which it is attached, in order to make it easier to peel off the resin film 20 from the adhesive layer 23.

[0044] <Method of manufacturing the microfluidic chip> Next, a method for manufacturing micro-channel chip 100 according to this embodiment will be described with reference to Fig. 3 and Fig. 4. Fig. 3 is a schematic enlarged cross-sectional view of resin film 20 or micro-channel chip 100 in each of the peeling step, pre-bonding heating step, and bonding step of the method for manufacturing micro-channel chip 100 according to this embodiment, and Fig. 4 is a schematic enlarged cross-sectional view of resin film 20 in the pre-bonding heating step of a modified example of the method for manufacturing micro-channel chip 100 according to this embodiment.

[0045] The manufacturing method of the microchannel chip 100 according to this embodiment is characterized by including a pre-bonding heating step in which the resin film 20 before being bonded to the resin substrate 10 is heated for 1 to 300 seconds at a temperature within a range of ±20°C around the glass transition point (Tg) of the resin material constituting the base layer 21 of the resin film 20, and a bonding step in which the adhesive layer 23 of the heated resin film 20 after the pre-bonding heating step is bonded by pressure bonding to the surface of the resin substrate 10 on which the flow channel 11 is formed.

[0046] The manufacturing method of the microchannel chip 100 according to this embodiment may include any step other than the pre-bonding heating step and the bonding step described above, as long as the steps do not affect the effects of the present invention. For example, the manufacturing method may include a step of cleaning the resin substrate 10 before bonding, and a combination step of combining and composing a membrane, a pump, a valve, a sensor, a motor, a mixer, a gear, a clutch, a microlens, an electric circuit, and the like.

[0047] In addition, in the method for manufacturing the micro-channel chip 100 according to this embodiment, the resin film 20 and the resin substrate 10 of the above-described embodiment can be used. Here, the resin substrate 10 used in the manufacturing method of the micro-channel chip 100 according to this embodiment may have its surface roughness (Rz) adjusted by polishing or the like on the surface on which the channel groove 11 is formed (the surface to be joined to the adhesive layer 23 of the resin film 20) so that the square of the surface roughness (Rz) of the joining surface 30 of the resulting micro-channel chip 100 falls within a predetermined range.

[0048] <Pre-bonding heating process> Next, the pre-bonding heating step in the manufacturing method for the micro-channel chip 100 according to this embodiment will be described in detail.

[0049] In this pre-bonding heating step, as shown in (II) of Fig. 3, the resin film 20 before being bonded to the resin substrate 10 is heated for 1 to 300 seconds at a temperature within a range of ±20°C (a temperature of Tg-20°C or more and Tg+20°C or less) centered on the glass transition point (Tg) of the resin material constituting the base layer 21 of the resin film 20. This allows the hardness of the base layer 21 to be appropriately reduced (softened) and the viscosity of the adhesive component of the adhesive layer 23 to be appropriately reduced, resulting in a resin film 20 that sufficiently follows the resin substrate 10 in the bonding step described below. The resin film 20 can be heated by directly contacting the resin film 20 with a heat source such as a heater 300 (for example, (II) of Fig. 3) or by heating the resin film 20 through the atmosphere or medium of the resin film 20 with a heat source (for example, Fig. 4).

[0050] Here, the heating temperature is the temperature of the heat source when the resin film 20 to be heated is in direct contact with the heat source, and is the temperature of the atmosphere or medium in contact with the resin film 20 when the resin film 20 to be heated is not in direct contact with the heat source. Since the resin film 20 is more easily brought into a state suitable for bonding, the heating temperature is more preferably within a range of ±15°C, and even more preferably within a range of ±10°C, centered on the glass transition point (Tg) of the resin material constituting the base layer 21 of the resin film 20. For the same reason, the lower limit of the heating time is more preferably 2 seconds or more, more preferably 3 seconds or more, and even more preferably 5 seconds or more. The upper limit of the heating time is also more preferably 270 seconds or less, more preferably 240 seconds or less, and even more preferably 210 seconds or less. When the surface roughness (Rz) of the surface of the resin substrate 10 to be bonded to the resin film 20 is relatively large, it is preferable to adjust the heating temperature and heating time in a region close to the upper limit within the above range.

[0051] In particular, in this pre-bonding heating step, it is more preferable to heat the resin film 20 in which the surface of the adhesive layer 23 to be bonded to the resin substrate 10 is exposed. Since there is no need to peel off the release film 25 after heating, the state of the heated adhesive layer 23 is easily maintained until the bonding step described later, and the resin substrate 10 can be bonded while maintaining the state of the heated adhesive layer 23, and the conformity of the resin film 20 to the resin substrate 10 is further improved. For example, it is preferable to heat the resin film 20 in this pre-bonding heating step, in which the release film 25 attached to the adhesive layer 23 is peeled off in the peeling step ((I) of FIG. 3). In addition, this peeling step and the pre-bonding heating step may be performed consecutively. However, in the manufacturing method of the micro-channel chip 100 according to this embodiment, the resin film 20 with the release film 25 is heated in the pre-bonding heating step, and then the release film 25 is peeled off. Here, in this embodiment, "the surface of the adhesive layer 23 is exposed" means that of the surface of the adhesive layer 23 to be joined to the surface of the resin substrate 10 on which the flow path groove 11 is formed, 70% or more of the surface area is exposed (not in contact with or stacked on other layers, etc.), it is more preferable that 80% or more of the surface area is exposed, even more preferable that 90% or more of the surface area is exposed, and even more preferable that 100% of the surface area is exposed.

[0052] In addition, in this pre-bonding heating step, it is more preferable to heat the resin film 20 by a heat source provided on the side opposite to the side of the adhesive layer 23 to be bonded to the resin substrate 10. For example, in the case of a resin film 20 having an adhesive layer 23 on one surface of the base material layer 21 and not having an adhesive layer 23 on the other surface, heating is performed by a heat source provided on the side of the base material layer 21 (opposite to the side of the adhesive layer 23). This is because in this pre-bonding heating step, the base material layer 21 of the resin film 20 becomes more flexible and is easily brought into a state suitable for bonding, and the viscosity of the adhesive layer 23 to be bonded to the resin substrate 10 is appropriately reduced, and the resin film 20 is more easily able to follow the resin substrate 10 in the bonding step described later. Specifically, examples of such a process include a process in which a resin film 20 has an adhesive layer 23 on one surface of the base material layer 21 and has no layers other than the base material layer 21, such as the adhesive layer 23, on the other surface, and heats the surface of the base material layer 21 (the other surface mentioned above) by directly contacting it with a heater (e.g., (II) in Figure 3), and a process in which the resin film 20 is not in contact with the surface of the base material layer 21 but is heated via the atmosphere by a heater that is installed approximately parallel to this surface on the surface side (e.g., Figure 4).

[0053] Furthermore, in this pre-bonding heating step, it is more preferable to heat the resin film 20 at a temperature higher than the glass transition point (Tg) of the adhesive component constituting the adhesive layer 23 to be bonded to the resin substrate 10. In the case of the adhesive layer 23 constituted by an adhesive component having a Tg close to the Tg of the resin material constituting the base layer 21, it is easier to reduce the viscosity of the adhesive layer 23 to be bonded to the resin substrate 10 in this pre-bonding heating step, and the ability of the resin film 20 to follow the resin substrate 10 in the subsequent bonding step is improved.

[0054] <Joining process> Next, the bonding step in the manufacturing method for the micro-channel chip 100 according to this embodiment will be described in detail.

[0055] In this bonding step, as shown in FIG. 3 (III), the adhesive layer 23 of the resin film 20 heated in the pre-bonding heating step is bonded to the surface of the resin substrate 10 on which the flow channel 11 is formed. Specifically, the resin substrate 10 and the heated resin film 20 are bonded to the surface of the resin substrate 10 on which the flow channel 11 is formed so as to cover the adhesive layer 23 of the resin film 20, thereby obtaining the micro-channel chip 100. The resin substrate 10 and the resin film 20 can be bonded to each other using a press machine or the like, but unlike bonding by thermal fusion, bonding is performed by the adhesiveness of the adhesive layer 23, so heating to melt the resin is not performed during bonding. However, this bonding step is started before the effect of heating the resin film 20 in the pre-bonding heating step described above is lost, that is, as soon as possible after the pre-bonding heating step. In particular, it is preferable to start the bonding step while the temperature of the resin film 20 is within a range of ±20°C around the glass transition point (Tg) of the resin material constituting the base layer 21.

[0056] In this bonding process, not only one resin substrate 10 and one resin film 20 as shown in FIG. 1 can be bonded to a resin substrate 10 having flow path grooves 11 formed on both sides thereof, but also a resin film 20 can be bonded to each of the two sides thereof, or a resin film 20 having adhesive layers 23 on both surfaces of a base layer 21 can be bonded to the adhesive layers 23 of two different resin substrates 10 on which flow path grooves 11 are formed.

[0057] As described above, in micro-channel chip 100 obtained by the method for producing a micro-channel chip according to the embodiment described above, the square of the surface roughness (Rz) of bonding surface 30, which is the surface where resin substrate 10 and adhesive layer 23 of resin film 20 are bonded, is X (μm 2 ), 100μm of the joint surface 30 2 The total film floating area of ​​the resin film 20 per unit area is expressed as Y (μm 2), the relationship (1) Y≦0.64X-12.2, the relationship (2) X≧23.0, and the relationship (3) Y≦20.0 are all satisfied. Furthermore, this micro-channel chip 100 is less susceptible to air bubble generation and residual air bubbles during liquid delivery to flow channel 11 and during storage after liquid delivery.

[0058] The above embodiment encompasses the following technical ideas. <1> The present invention comprises a resin substrate having a flow channel formed on at least one surface thereof, and a resin film having a base layer and an adhesive layer, the resin film being bonded to the resin substrate so as to cover the flow channel with the adhesive layer, and the square of the surface roughness (Rz) of the bonding surface where the resin substrate and the adhesive layer of the resin film are bonded is defined as X (μm 2 ), the bonding surface is 100 μm 2 The total film floating area of ​​the resin film per unit area is expressed as Y (μm 2 ) the microchannel chip satisfies all of the following relational expressions (1) to (3). (1) Y≦0.64X-12.2 (2) X≧23.0 (3) Y≦20.0 <2> The square of the surface roughness (Rz) of the joining surface is 30.25 or more (X≧30.25), <1> The microchannel chip according to claim 1 . <3> The square of the surface roughness (Rz) of the joining surface is 56.25 or less (X≦56.25), <1> or <2> The microchannel chip according to claim 1 . <4> The base layer of the resin film is made of any one selected from the group consisting of polystyrene-based resins, polycarbonate-based resins, polyacrylic-based resins, and cyclic olefin-based resins. <1> ~ <3> 13. The microchannel chip according to claim 12, <5> A method for manufacturing a micro-channel chip comprising: a resin substrate having a flow channel formed on at least one surface thereof; and a resin film having a base layer and an adhesive layer, the resin film being bonded to the resin substrate so as to cover the flow channel with the adhesive layer, the method comprising: a pre-bonding heating step of heating the resin film before being bonded to the resin substrate at a temperature within a range of ±20°C around the glass transition point (Tg) of a resin material constituting the base layer of the resin film for 1 to 300 seconds; and a bonding step of bonding the adhesive layer of the heated resin film after the pre-bonding heating step to the surface of the resin substrate on which the flow channel is formed by pressure bonding. <6> In the pre-bonding heating step, the resin film with the surface of the adhesive layer exposed is heated. <5> A method for producing the microchannel chip according to claim 1. <7> In the pre-bonding heating step, the resin film is heated by a heat source provided on the side opposite to the adhesive layer. <5> or <6> A method for producing the microchannel chip according to claim 1. <8> In the pre-bonding heating step, the resin film is heated at a temperature higher than the glass transition point (Tg) of the adhesive component constituting the adhesive layer. <5> ~ <7> 13. A method for producing a microchannel chip according to any one of the above items. <9> The base layer of the resin film to be heated in the pre-bonding heating step is made of any one selected from the group consisting of polystyrene-based resins, polycarbonate-based resins, polyacrylic-based resins, and cyclic olefin-based resins. <5> ~ <8> 13. A method for producing a microchannel chip according to any one of the above items. EXAMPLES

[0059] Hereinafter, examples of the present invention will be described, however, the present invention is not limited to the following examples, and various modifications are possible within the technical concept of the present invention.

[0060] Two kinds of rectangular resin substrates made of polyacrylic resin and having flow channel formed on one surface, with different surface roughness (Rz) of the surface on which the flow channel was formed, and a resin film having a base layer made of polyacrylic resin and an adhesive layer on one surface thereof (base layer: thickness 125 μm, Tg of constituent resin material (PMMA) 100°C, adhesive layer: thickness 10 μm, Tg of constituent adhesive component (polyacrylic adhesive) 10°C) were prepared. Then, before bonding with the resin substrate, the resin film was placed so that the base layer side was in contact with a stainless steel shelf of an oven (Tokyo Rikakikai Co., Ltd., constant temperature blower dryer WFO-520) with the adhesive layer exposed, and heated at a temperature of 100°C for 2 minutes (120 seconds). Then, the heated resin film was pressure-bonded to the surface on which the flow channel was formed of the resin substrate through the adhesive layer, and two kinds of microchannel chips according to the embodiment were manufactured (samples 2 and 4). Two types of microchannel chips according to comparative examples were also manufactured in the same manner as in the above-mentioned examples, except that the resin film was not heated (pre-bonding heating step was not included). The surface roughness (Rz) of the bonding surfaces was measured non-contact using a Keyence VK-9710 laser microscope, and as shown in Table 1 below, the surface roughness (Rz) of the bonding surfaces of Samples 1 and 2 was 6.346 μm, and the surface roughness (Rz) of the bonding surfaces of Samples 3 and 4 was 5.007 μm.

[0061] The bonding surface between the resin substrate and the resin film of the four types of micro-channel chips according to the examples and comparative examples was observed and photographed using a laser microscope (Keyence Corp., VK-9710, magnification 50 times), and the total area of ​​the film lifting was calculated using analysis software (Keyence Corp., VK-Analyzer). The results are shown in Table 1 and FIG. 5 (black circles), and the photographed images are shown in FIGS. 6 to 7. The photographed images of the micro-channel chip with a bonding surface roughness (Rz) of 6.346 μm are shown in FIG. 6 ((a) of FIG. 6 is sample 1, and (b) of FIG. 6 is sample 2), and the photographed images of the micro-channel chip with a bonding surface roughness (Rz) of 5.007 μm are shown in FIG. 7 ((c) of FIG. 7 is sample 3, and (d) of FIG. 7 is sample 4). In both the photographed images in FIG. 6 and FIG. 7, the side on which the flow channel is formed (flow channel side) is shown as a reference, and the light-colored parts in both images are the film lifting parts.

[0062] As a result, by heating the resin film under predetermined conditions before bonding, the total area of ​​film floating on the bonding surface was significantly reduced in all of the micro-channel chips of the Examples (Samples 2 and 4) compared to the micro-channel chips of the Comparative Examples (Samples 1 and 3) (Table 1, Figures 5 to 7). In particular, in the micro-channel chip with a larger surface roughness (Rz) of 6.346 μm on the bonding surface, Sample 1, which was manufactured without heating the resin film before bonding, had a film floating area of ​​100 μm on the bonding surface. 2 The total area of ​​the film floating per unit is 27.68μm 2 When liquid was pumped into the flow channel and stored at room temperature (25°C), air bubbles were generated and remained. However, in sample 2, which was manufactured by heating the resin film before bonding and then bonding, the air bubbles were generated and remained in the 100 μm bonded area. 2 The total area of ​​the film floating per unit is 12.65μm 2 (The percentage was 12.65%) (Table 1, FIG. 6(b), etc.), and even when liquid was pumped into the flow channel and stored at room temperature (25°C), there was almost no generation or residual bubbles.

[0063] [Table 1] [Explanation of symbols]

[0064] 10 Resin substrate 11 Flow channel 13 Ports 20 Resin film 21 Base material layer 23 Adhesive layer 25 Release film 30 Joint surface 100 Microfluidic Chip 300 Heater D Channel depth W Channel width

Claims

1. A resin substrate having a flow channel formed on at least one surface thereof; A method for manufacturing a microchannel chip comprising: a resin film having a base layer and an adhesive layer, the resin film being bonded to the resin substrate by the adhesive layer so as to cover the channel groove, the method comprising: a pre-bonding heating step of heating the resin film before being bonded to the resin substrate at a temperature within a range of ±20° C. centered on the glass transition point (Tg) of the resin material constituting the base layer of the resin film for 1 to 300 seconds; a bonding process of bonding the adhesive layer of the resin film, which has been heated after the pre-bonding heating process, to a surface of the resin substrate on which the flow channel is formed by pressure bonding; A method for producing a microchannel chip comprising the steps of:

2. The method for producing a micro-channel chip according to claim 1 , wherein the resin film with the surface of the adhesive layer exposed is heated in the pre-bonding heating step.

3. 3. The method for producing a micro-channel chip according to claim 1, wherein in the pre-bonding heating step, the resin film is heated by a heat source provided on a side opposite to the adhesive layer.

4. The method for manufacturing a microchannel chip according to any one of claims 1 to 3, wherein in the pre-bonding heating step, the resin film is heated at a temperature higher than the glass transition point (Tg) of an adhesive component constituting the adhesive layer.

5. The method for manufacturing a microchannel chip according to any one of claims 1 to 4, wherein the base material layer of the resin film heated in the pre-bonding heating step is composed of any one selected from the group consisting of polystyrene-based resins, polycarbonate-based resins, polyacrylic-based resins, and cyclic olefin-based resins.

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