JP7732178B2 - Microfluidic chip - Google Patents

Description

The present invention relates to a microchannel chip used in the pharmaceutical industry, etc.

In fields such as the pharmaceutical industry, which manufactures pharmaceuticals and reagents, microchannel chips are sometimes used for the analysis, synthesis, and screening of nucleic acids, proteins, sugar chains, etc. These microchannel chips utilize microfabrication techniques to form minute flow channels (also called microchannels) in a substrate made of resin or other materials, and within the minute space containing these microchannels, chemical reactions, separation, detection, analysis, and other processes can be carried out on samples (see, for example, Patent Document 1).

Many microchannel chips used for such analyses include a substrate (resin substrate) made of resin with microchannels or the like formed on its surface, and a resin film bonded to the resin substrate. The resin substrate and resin film are primarily bonded together by heat fusion or by adhesion using an adhesive layer on the resin film.

Japanese Patent Application Laid-Open No. 2014-206512

However, when a resin substrate and a resin film are bonded together using an adhesive layer (bonding via an adhesive layer), areas where the adhesive layer does not sufficiently conform to the resin substrate (areas with low conformability) are likely to occur on the bonding surface. In other words, the film is likely to float slightly at the bonding surface. This causes the problem that gas can enter the flow channel from these slightly floating areas during or after liquid delivery to the flow channel, generating and remaining bubbles that can interfere with liquid delivery, chemical reactions, separation, and detection. In particular, there are cases where liquid is delivered to the flow channel of a microchannel chip that has been stored in a low temperature range (0-10°C) beforehand, or where the microchannel chip is stored at around 35-40°C (e.g., near body temperature) after liquid delivery to the flow channel. In such cases, the above-mentioned problem tends to occur more easily.

The present invention was made in consideration of the above-mentioned problems, and aims to provide a microchannel chip that minimizes the generation and residual bubbles during liquid transfer to the channel and during storage after liquid transfer.

The microchannel chip of the present invention comprises a resin substrate having a channel groove formed on at least one surface, and a resin film having a base layer and an adhesive layer, the base layer being bonded to the resin substrate so as to cover the channel groove. When the thickness of the base layer of the resin film is X (μm) and the thickness of the adhesive layer is Y (μm), the chip is characterized by satisfying the following relationship: Y≧0.4X-25; (2) 50≧Y≧3; and (3) X≧40.

The present invention makes it possible to obtain a microchannel chip in which the adhesive layer of the resin film has high conformability to the resin substrate at the bonding surface, and which generates and retains minimal air bubbles during liquid transfer to the channel and during storage after liquid transfer.

FIG. 2 is an enlarged cross-sectional view showing the vicinity of a channel groove of the microchannel chip according to the present embodiment. FIG. 1 is a front view of a micro-channel chip according to an embodiment of the present invention. 1 is a graph showing the state of bubble generation when water is pumped into the flow channel of the micro-channel chips of Samples 1 to 9 shown in the Examples (after refrigerated storage) and the chips are stored at 37°C for 1 hour, and the graph shows the relationship between the thickness of the base layer (X: μm) and the thickness of the adhesive layer (Y: μm) of the resin film in the micro-channel chip. 10 is a photograph (drawing substitute photograph) of a microchannel chip of Sample 1 shown in the Examples (after refrigerated storage) in which water was pumped into the channel grooves and stored at 37° C. for 1 hour. 10 is a photograph (drawing substitute photograph) of a microchannel chip of Sample 9 shown in the example (after refrigerated storage) in which water was pumped into the channel grooves and stored at 37° C. for 1 hour.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of a microchannel chip and a method for manufacturing the same according to the present invention will be described with reference to the drawings.
The embodiment described below is merely an example to facilitate understanding of the present invention, and is not intended to limit the present invention. In other words, the shapes, dimensions, arrangements, etc. of the components described below may be changed 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 where appropriate. Note that in all drawings, some parts are not given reference numerals (omitted) for convenience. Furthermore, the dimensional ratios of each component shown in the drawings may differ from the actual dimensional ratios in order to facilitate understanding of the invention.

<Overview>
First, an overview of the micro-channel chip according to this embodiment will be described with reference to Fig. 1 and Fig. 2. Fig. 1 is a schematic enlarged cross-sectional view of the vicinity of a channel groove 11 of a micro-channel chip 100 according to this embodiment. Fig. 2 is a front view of the micro-channel chip 100 according to this embodiment.

As shown in Figures 1 and 2, the microchannel chip 100 according to this embodiment comprises a resin substrate 10 having a flow channel 11 formed on at least one surface thereof, and a resin film 20 having a base layer 21 and an adhesive layer 23, the resin film 20 being bonded to the resin substrate 10 with the adhesive layer 23 so as to cover the flow channel 11. Furthermore, when the thickness of the base layer 21 of the resin film 20 is X (μm) and the thickness of the adhesive layer 23 bonded to the resin substrate 10 is Y (μm), the microchannel chip 100 satisfies the following relationship: Y ≧ 0.4X-25; (2) 50 ≧ Y ≧ 3; and (3) X ≧ 40.

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 Figures 1 and 2. Alternatively, the microchannel chip 100 may have a configuration in which flow channel 11 is formed on both sides of the resin substrate 10 and resin films 20 having the above-described characteristics are bonded to both sides, or a configuration in which both surfaces of the base layer 21 of the resin film 20 are provided with adhesive layers 23 having thicknesses that satisfy the above-described relationship, and the surfaces of the resin substrate 10 on which the flow channel 11 is formed are bonded to both of these adhesive layers 23.

In addition, the microchannel chip 100 according to this embodiment may have one or more ports 13 formed on at least one surface of the resin substrate 10, which may serve as an inlet or outlet for a sample or the like, or a degassing port, as shown in FIG. 2. The port 13 may be cylindrical as shown in FIG. 2, or may have another shape such as a rectangular cylinder, and may even be formed to penetrate the resin substrate 10.

Furthermore, the overall shape (external shape) of the microchannel chip 100 according to this embodiment is preferably a rectangular plate shape from the viewpoint of ease of use in devices, 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.

The microchannel chip 100 according to this embodiment is characterized in that, even if the surface roughness (Rz: maximum height roughness) of the bonding surface 30, which is the surface where the surface of the resin substrate 10 on which the flow channel 11 is formed and the adhesive layer 23 of the resin film 20 are bonded, is, for example, 5 μm or more, or even 5.5 μm or more, or even 6 μm or more, or even more than 7 μm, or even 8 μm or more, or even 9 μm or more, or even 10 μm or more, the thickness (X) of the base layer 21 of the resin film 20 and the thickness (Y) of the adhesive layer 23 have the above-described configuration, the adhesive layer 23 of the resin film 20 has high conformability to the resin substrate 10 at this bonding surface 30. Therefore, in manufacturing the microchannel chip 100 according to this embodiment, adjustment to reduce the surface roughness (Rz) of the surface of the resin substrate 10 on which the flow channel 11 is formed (the surface bonded to the adhesive layer 23 of the resin film 20) may be omitted. However, in order to ensure that the effects of the present invention are fully realized, it is more preferable that the surface roughness (Rz) of this joining surface 30 be 20 μm or less, even more preferably 18 μm or less, and even more preferably 15 μm or less.

In conventional microchannel chips, if the surface roughness (Rz) of this bonding surface is above a certain level, there may be many areas on this bonding surface where the adhesive layer of the resin film does not sufficiently conform to the surface of the resin substrate to be bonded and floats slightly away (micro-floating of the film). However, in the microchannel chip 100 of this embodiment, even if the surface roughness (Rz) of the bonding surface 30 is above a certain level, the thickness (X) of the base layer 21 of the resin film 20 and the thickness (Y) of the adhesive layer 23 bonded to the resin substrate 10 satisfy all of the relationship equations (1) to (3) described above. This means that the adhesive layer 23 of the resin film 20 is bonded to the surface of the resin substrate 10 while sufficiently conforming to it, and there is extremely little micro-floating of the film on the bonding surface 30 (particularly the bonding surface 30 near the flow channel 11).
Micro-channel chip 100 according to the present embodiment, which is configured as described above, experiences extremely little gas intrusion into flow channel 11 from bonding surface 30 during liquid transfer to flow channel 11 and during storage of micro-channel chip 100 after this liquid transfer, resulting in very little generation or residual air bubbles in flow channel 11. Furthermore, there are cases where the micro-channel chip is stored in a refrigerator before liquid transfer to the flow channel, or where the micro-channel chip is stored (incubated, etc.) at about 35 to 40°C for several tens of minutes to several hours after liquid transfer to the flow channel. Even in such cases, micro-channel chip 100 according to the present embodiment is unlikely to experience minute floating of resin film 20 at bonding surface 30, and similarly, there are very few generation or residual air bubbles in flow channel 11.

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 mean line, and the sum of the maximum peak height Zp and the maximum valley depth Zv of the roughness curve in this extracted portion is expressed in μm.
The surface roughness (Rz) is measured using a non-contact measuring device (such as a laser microscope VK-9710 manufactured by Keyence Corporation) on the measurement surface (such as the joining surface 30 in the present invention).

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

The resin substrate 10 of the microchannel chip 100 according to this embodiment is a plate-shaped substrate made of resin with a channel groove 11 formed on at least one surface. Its dimensions, for example, if rectangular, are approximately 10 mm to 100 mm x 10 mm to 200 mm, and a thickness of 0.5 mm to 3.0 mm.

Furthermore, the flow channel 11 formed in the resin substrate 10 is a fine channel with an opening width and depth that allow the passage of a liquid sample. For example, the opening width (opening length in the short direction of the flow channel 11: the length of the portion indicated by W in the embodiments of Figures 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 (by cutting or adding components).

Furthermore, the shape of the flow channel 11 is not particularly limited, and the cross-sectional shape may be rectangular, polygonal, or semicircular. However, a trapezoidal or semicircular cross-sectional shape is preferred, as this facilitates stable liquid transfer. Furthermore, the number of flow channel 11 formed in the resin substrate 10 is not limited to one; multiple channels may be formed in series or parallel. Furthermore, the flow channel 11 may branch or intersect, and the cross-sectional shape, number, opening width, depth, and other factors can be designed as appropriate depending on the intended use.

Here, the depth of the flow channel 11 formed in the resin substrate 10 of the microchannel chip 100 according to this embodiment refers to the length of the flow channel 11 in the thickness direction of the resin substrate 10. In other words, it is the longest distance between the point where 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 was formed, and the point where the perpendicular line intersects with the surface that constitutes the flow channel 11. For example, in the embodiment shown in FIG. 1, the depth of the flow channel 11 is the longest distance between the two points where a perpendicular line is drawn from the upper side of the flow channel 11 (the imaginary outer surface on the resin film 20 side) to the lower side of the resin substrate 10 before the resin film 20 is bonded, and the point where the perpendicular line intersects with the lower side of the flow channel 11 (the bottom surface that constitutes the flow channel 11, which has an inverted trapezoidal cross section) (D in FIG. 1).

Furthermore, the surface of the flow channel 11 of the resin substrate 10 (the surface that constitutes the flow channel 11) may be subjected to a surface treatment such as hydrophilization or the formation of surface-treated functional groups. Examples of such surface treatments include the introduction of oxygen-containing functional groups. The introduction of these oxygen-containing functional groups improves the hydrophilicity of the surface, allowing for smoother passage of samples (including water or hydrophilic solvents). Examples of oxygen-containing functional groups include polar functional groups such as carbonyl groups (e.g., aldehyde groups and ketone groups), carboxyl groups, hydroxyl groups, ether groups, peroxide groups, and epoxy groups. Examples of the introduction process include plasma treatment, corona discharge treatment, excimer laser treatment, and flame treatment. This surface treatment may also be applied to the surface of the resin film 20 (the surface of the adhesive layer 23) that covers the flow channel 11, as described below.

The resin substrate 10 is made of a resin material. Here, "made of a resin material" means that the resin material is the primary material (the resin material accounts for 60% by mass or more of the total mass of the resin substrate 10, more preferably 70% by mass or more, even more preferably 80% by mass or more, and even more preferably 90% by mass or more). While the resin substrate 10 may have a layer made of a material other than a resin material (such as glass) on a portion of the side not bonded to the resin film 20, it is preferable that the entire resin substrate 10 be made of a resin material (especially the same resin material). This is because this makes it easier to mold the resin substrate 10 itself. Furthermore, the flow channel 11 may be formed on both surfaces of the resin substrate 10.

Resin materials used to fabricate this 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 resin materials may be used alone or in combination. Resin substrate 10 can be constructed primarily from such resin materials.

In particular, because it is easier to ensure 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).

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

The resin film 20 of the microchannel chip 100 according to this embodiment has a base layer 21, which serves as the base material (the film's basic material), and an adhesive layer 23 containing an adhesive component, and is configured such that the base layer 21 and the adhesive layer 23 are laminated together. 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 layer 21 may be a single layer (single layer), or may be configured such that multiple base layers are laminated together. The adhesive layer 23 is provided on at least one surface of the base layer 21, but the base layer 21 may also be configured such that the adhesive layer 23 is provided on both surfaces of the base layer 21, or such that the adhesive layer 23 is formed in a specific pattern (pattern coating) on one surface of the base layer 21. Furthermore, other layers (such as coating layers or adhesive layers (laminate adhesive layers)) may be included between the base material layer 21 and the adhesive layer 23, on the surface of the base material layer 21 facing (opposite) the surface that is bonded to the resin substrate 10, or between layers of the base material layer 21 that are made up of multiple laminated base material layers.

The size of this resin film 20, if it is rectangular, can be, for example, the same as that of the resin substrate 10 described above, that is, 10 mm to 100 mm x 10 mm to 200 mm. From the viewpoint of ease of bonding to the resin substrate 10, the overall thickness of the resin film 20 is preferably such that the lower limit is 0.01 mm or more, more preferably 0.02 mm or more, and even more preferably 0.03 mm or more, while the thickness (X) of the base material layer 21 and the thickness (Y) of the adhesive layer 23 bonded to the resin substrate 10 satisfy all of the relational expressions (1) to (3) described below. Furthermore, since the upper limit is unlikely to affect the conformability of the resin film 20 to the resin substrate 10 at the bonding surface 30, 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, while the thickness (X) of the base material layer 21 and the thickness (Y) of the adhesive layer 23 bonded to the resin substrate 10 satisfy all of the relational expressions (1) to (3) described below.
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 10 locations in the direction of the normal vector of the main surfaces of the resin film 20 and calculating the average.

The resin film 20 of the microchannel chip 100 according to this embodiment is configured so that the thickness (X: μm) of the base layer 21 and the thickness (Y: μm) of the adhesive layer 23 bonded to the resin substrate 10 satisfy the following relations: (1) Y≧0.4X-25, (2) 50≧Y≧3, and (3) X≧40 (see FIG. 3). This configuration allows the adhesive layer 23 of the resin film 20 to adequately conform to the surface of the resin substrate 10 on which the flow channel 11 is formed (the surface to be bonded) at the bonding surface 30, resulting in very little film lift at the bonding surface 30. In a resin film 20 having adhesive layers 23 on both surfaces of the base layer 21, it is sufficient that the thickness (X) of the base layer 21 and the thickness (Y) of one of the adhesive layers 23 bonded to the resin substrate 10 satisfy the above-mentioned relationship formulas (1) to (3). However, in a case where both adhesive layers 23 are bonded to the resin substrate 10, the thickness (X) of the base layer 21 and the thickness (Y) of each adhesive layer 23 must individually (independently) satisfy the above-mentioned relationship formulas (1) to (3). In other words, the above-mentioned relationship formulas (1) to (3) are the relationship formulas between the thickness (X) of the base layer 21 of the resin film 20 and the thickness (Y) of the adhesive layer 23 bonded to the resin substrate 10 on one side of the base layer 21.

In addition, from the viewpoint of further improving the conformability of the bonding surface 30 of the resin film 20 of the microchannel chip 100 according to this embodiment to the surface of the resin substrate 10 on which the channel grooves 11 are formed, it is more preferable that the thickness (X) of the base layer 21 and the thickness (Y) of the adhesive layer 23 further satisfy the relationship (4) Y ≥ 0.4X - 22, and even more preferable that the relationship (5) Y ≥ 0.4X - 20.

The thickness (X) of the base layer 21 of the resin film 20 preferably has a lower limit of 45 μm or more (X≧45), more preferably 50 μm or more (X≧50), and even more preferably 70 μm or more (X≧70). The upper limit is preferably 130 μm or less (130≧X), more preferably 125 μm or less (125≧X), even more preferably 110 μm or less (110≧X), even more preferably less than 100 μm (100>X), even more preferably less than 90 μm (90>X), and even more preferably 85 μm or less (85≧X). For example, a preferred range for X is 50 μm or more and 130 μm or less (130≧X≧50). In manufacturing the microchannel chip 100 according to this embodiment, the resin film 20 has a suitable hardness, making it easy to bond to the resin substrate 10, and the resin film 20 maintains a high degree of conformability to the resin substrate 10 at the bonding surface 30 of the obtained microchannel chip 100.
Here, the thickness (X) 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 locations in the direction of the normal vector of the main surfaces of the base material layer 21 and calculating the average (X in FIG. 1 is shown to facilitate understanding of the thickness of the base material layer 21). Note that, when the base material layer 21 has a configuration in which a plurality of base material layers are stacked, the thickness (X) of the base material layer 21 is the sum of the thicknesses of the stacked base material layers calculated in the same manner as above.

Furthermore, the thickness (Y) of the adhesive layer 23 of the resin film 20 preferably has a lower limit of 5 μm or more (Y≧5), more preferably greater than 10 μm (Y>10), even more preferably 15 μm or more (Y≧15), and even more preferably 20 μm or more (Y≧20). The upper limit is preferably 45 μm or less (45≧Y), more preferably 40 μm or less (40≧Y), even more preferably 35 μm or less (35≧Y), and even more preferably 30 μm or less (30≧Y). For example, a preferred range for Y is 5 μm or more and 40 μm or less (40≧Y≧5). This is because even if the surface roughness (Rz) of the surface of the resin substrate 10 on which the flow channel 11 is formed before bonding is equal to or greater than a certain level, the resin film 20 at the bonding surface 30 of the resulting micro-channel chip 100 will have high conformability to the resin substrate 10, and the bonded adhesive layer 23 will be less likely to bulge into the flow channel 11, making it less likely that the internal volume of the flow channel 11 will decrease (leading to a flow channel 11 with more stable liquid delivery speeds, etc.).
Here, the thickness (Y) of the adhesive layer 23 is determined 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 10 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 (Y in FIG. 1 is shown to make it easier to understand the thickness of the adhesive layer 23). Therefore, in the case of a resin film 20 in which adhesive layers 23 are provided on both surfaces of the base layer 21, the thickness (Y) of the adhesive layer 23 is the thickness of the adhesive layer 23 on one surface (one side) bonded to the resin substrate 10, and is not the sum of the thicknesses of the adhesive layer 23 on both surfaces.

Resin materials used for the base layer 21 of this resin film 20 include, for example, the same resin materials used for the resin substrate 10, such as 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 resins may be used alone or in combination. When using two or more resins in combination, two or more resin materials may be mixed, or two or more layers formed from a single resin material may be laminated together. 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 comprises 60% by mass or more of the total mass of the base material layer 21, more preferably 70% by mass or more, even more preferably 80% by mass or more, and even more preferably 90% by mass or more).

In addition, since this makes it easier to achieve the effects of the present invention and ensures the transparency of the resin film 20, similar to the resin substrate 10 described above, it is preferable that the base layer 21 be made of (used as the main material 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 it be made of any one selected from the group consisting of polystyrene (PS), polycarbonate (PC), polymethyl methacrylate (PMMA), and cycloolefin copolymer (COC).

Furthermore, if the aforementioned resin substrate 10 and the 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 more preferable from the standpoint of ensuring the transparency of the resulting microchannel chip 100 (ease of observation, etc.).

The adhesive component used in the adhesive layer 23 of the resin film 20 can be one or more selected from, for example, 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 can be formed using such an adhesive component as the main component (for example, comprising 60% by weight or more of the total weight of the adhesive layer 23, more preferably 70% by weight or more, even more preferably 80% by weight or more, and even more preferably 90% by weight or more).

It is highly preferable that the adhesive component constituting the adhesive layer 23 is a polyacrylic resin (acrylic adhesive), because the properties of the acrylic adhesive make it easier for the resin film 20 to conform to the surface of the resin substrate 10 on which the flow channel 11 is formed, in an adhesive layer 23 with a thickness that satisfies the aforementioned relationship. In this case, it is even more preferable that the resin substrate 10 is also made of the same type of resin material, a polyacrylic resin.

The resin film 20 of the microchannel chip 100 according to this embodiment may further contain additives such as plasticizers, antioxidants, flame retardants, antistatic agents, pigments, and dyes, as long as the effects of the present invention are not impaired. The same applies to the resin substrate 10 described above.

Furthermore, this resin film 20 may have electrode portions formed by metal vapor deposition or thin metal films, for example, to correspond to the flow channel grooves 11 and ports 13 formed in the resin substrate 10.

<Method of manufacturing the microfluidic chip>
Next, a method for manufacturing the micro-channel chip 100 according to this embodiment will be described.

The microchannel chip 100 according to this embodiment is manufactured by bonding the above-described resin substrate 10 and resin film 20 together by pressure bonding so that the adhesive layer 23 of the resin film 20 covers the surface of the resin substrate 10 on which the flow channel 11 is formed. This bonding process by pressure bonding the resin substrate 10 and resin film 20 can be carried out using a press or the like, but unlike a bonding process by heat fusion, bonding is achieved by the adhesiveness of the adhesive layer 23, so no heating that would melt the resin is performed during the bonding process.

As described above, the resin film 20 before bonding used in manufacturing the microchannel chip 100 according to this embodiment may be one in which the thickness (X) of the base material layer 21 and the thickness (Y) of the adhesive layer 23 bonded to the resin substrate 10 are adjusted in advance so that, after bonding to the resin substrate 10, i.e., in the state of a microchannel chip, the thickness (X) of the base material layer 21 and the thickness (Y) of the adhesive layer 23 bonded to the resin substrate 10 satisfy the relationship (1) Y ≧ 0.4X − 25, the relationship (2) 50 ≧ Y ≧ 3, and the relationship (3) X ≧ 40. In particular, a resin film 20 that is configured such that the thickness (X) of the base material layer 21 and the thickness (Y) of the adhesive layer 23 satisfy the relationship (1) Y ≧ 0.4X − 25, the relationship (2) 50 ≧ Y ≧ 3, and the relationship (3) X ≧ 40 even before bonding to the resin substrate 10 is preferred. Alternatively, the bonding conditions (pressure, etc.) for bonding the resin substrate 10 and the adhesive layer 23 of the resin film 20 may be adjusted so that the thickness (X) of the base layer 21 of the resin film 20 in the resulting microchannel chip 100 and the thickness (Y) of the adhesive layer 23 bonded to the resin substrate 10 both satisfy the above-mentioned relationship.

In addition, when manufacturing the microchannel chip 100 according to this embodiment, it is also possible to combine and integrate membranes, pumps, valves, sensors, motors, mixers, gears, clutches, microlenses, electrical circuits, etc.

The microchannel chip according to the present invention, including the embodiments described above, can be used for sample separation, detection, analysis, and the like, and can also bring two or more types of samples into contact with each other to carry out chemical reactions. Furthermore, the generation and persistence of air bubbles during liquid transfer to the channel and during storage after this liquid transfer are extremely low, making it extremely suitable for use. In particular, even when the microchannel chip is stored in a low-temperature range (0-10°C) beforehand, or when the microchannel chip is stored at a temperature near the body temperature range of a living body (35-40°C) after liquid transfer to the channel, slight lifting of the resin film at the bonding surface is unlikely to occur, and the above-mentioned effects are similarly achieved.

The above embodiment encompasses the following technical ideas.
<1> A microchannel 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 base layer and adhesive layer being bonded to the resin substrate so as to cover the flow channel, wherein when the thickness of the base layer of the resin film is X (μm) and the thickness of the adhesive layer is Y (μm), the chip satisfies all of the following relational expressions (1) to (3):
(1) Y≧0.4X-25
(2) 50 ≧ Y ≧ 3
(3) X≧40
<2> The micro-channel chip according to <1>, wherein the thickness X (μm) of the base layer of the resin film and the thickness Y (μm) of the adhesive layer further satisfy the following relational expression (4):
(4) Y≧0.4X-22
<3> The micro-channel chip according to <1> or <2>, wherein the thickness Y (μm) of the adhesive layer of the resin film is 40 μm or less (40≧Y).
<4> The micro-channel chip according to any one of <1> to <3>, wherein the thickness X (μm) of the base layer of the resin film is 50 μm or more and 130 μm or less (130≧X≧50).
<5> The micro-channel chip according to any one of <1> to <4>, wherein the adhesive layer of the resin film is made of a polyacrylic resin.
<6> The micro-channel chip according to any one of <1> to <5>, wherein 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.

The following describes examples of the present invention, but the present invention is not limited to these examples, and various modifications are possible within the technical concept of the present invention.

A 60 mm x 100 mm rectangular resin substrate was prepared, made of polyacrylic resin and having a flow channel formed on one surface (including a region with a flow channel opening width (W) of 200 μm and a flow channel depth (D) of 30 μm, the length of which was 10 mm or more). Various resin films of the same rectangular size as the resin substrate were also prepared, each with a base layer made of polyacrylic resin and an adhesive layer on one surface. These resin films were then pressure-bonded to the flow channel-formed surface of the resin substrate via the adhesive layer to produce nine microchannel chip samples (Samples 1-9) with different resin film base layer thicknesses (X) or adhesive layer thicknesses (Y). The surface roughness (Rz) of the bonded surface between the resin substrate and resin film for all samples was 12.476 μm. The surface roughness (Rz) of these bonded surfaces was measured non-contact using a Keyence VK-9710 laser microscope. The thickness of the base layer (X: μm) and adhesive layer (Y: μm) of the resin film for each sample are also shown in Table 1 below.

A liquid transport test was carried out to transport water into the channel using the microchannel chips of Samples 1 to 9. In this liquid transport test, each sample was stored in advance in a refrigerator (4°C) overnight (approximately 10 hours) and used at room temperature (25°C).
Then, for each microchannel chip sample, immediately after water delivery and after storage at 37°C for 1 hour after water delivery (after 1 hour at 37°C), the state of bubble generation in the region of the channel where the channel groove opening width (W) was 200 μm and the channel groove depth (D) was 30 μm was evaluated according to the following evaluation criteria. The results are also shown in Table 1 below. The results after 1 hour at 37°C are also shown in Figure 3.

The maximum number of bubbles generated per 10 mm of flow channel length is 1 or less: ○
The maximum number of bubbles generated per 10 mm of flow channel length is 2 or more: ×

In addition, the conditions of Sample 1 and Sample 9 in Table 1 above after 1 hour at 37°C were observed near the flow channel using a microscope (Olympus SZ61 stereomicroscope), and photographs were taken. These photographed images are shown in Figures 4 and 5. Figure 4 shows the photographed image of Sample 1, and Figure 5 shows the photographed image of Sample 9.

These results (particularly the graph in Figure 3) demonstrate that in microchannel chips obtained by bonding a resin substrate and a resin film together using an adhesive layer, when the thickness (X) of the base layer of the resin film and the thickness (Y) of the adhesive layer bonded to the resin substrate satisfy the relationship (1) Y ≥ 0.4X - 25, very little air bubbles are generated or remain in the channel, even when stored at 37°C after liquid delivery to the channel. For example, in the microchannel chips of Samples 1 and 2, up to two or more air bubbles were generated or remain per 10 mm in the channel region after 1 hour at 37°C (arrows in Table 1 and Figure 4), whereas in the microchannel chips of Samples 3 to 9, no air bubbles were generated or remain per 10 mm in the channel region, even under these conditions (Table 1 and Figure 5). Furthermore, with regard to the respective thicknesses of the base layer and adhesive layer of the resin film, it was found that the closer (smaller) the base layer thickness (X) of the resin film is to 50 μm, or the closer (larger) the adhesive layer thickness (Y) of the resin film is to 30 μm, the better the conformability between the adhesive layer of the resin film and the resin substrate, which is more preferable in terms of suppressing the generation and retention of air bubbles (Table 1, Figure 3).

10 Resin substrate 11 Flow channel 13 Port 20 Resin film 21 Base layer 23 Adhesive layer 30 Bonding surface 100 Micro-channel chip X Base layer thickness Y Adhesive layer thickness D Flow channel depth W Flow channel width

Claims (4)

a resin substrate having a flow channel formed on at least one surface thereof;
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 flow path groove;
A microchannel chip, wherein when the thickness of the base layer of the resin film is X (μm) and the thickness of the adhesive layer is Y (μm), the following relational expressions (2), (3), and (5) are all satisfied:
(2) 50 ≧ Y ≧ 30
(3) X≧50
(5) Y≧0.4X-20 2. The micro-channel chip according to claim 1 , wherein the adhesive layer of the resin film has a thickness Y (μm) of 40 μm or less (40≧Y). 3. The micro-channel chip according to claim 1 , wherein the adhesive layer of the resin film is made of a polyacrylic resin. The microchannel chip according to any one of claims 1 to 3 , wherein 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.