Microfluidic device

Abstract

To provide a microfluidic device in which liquid easily enters a micro flow path when the liquid such as a cell culture solution is injected into the micro flow path.SOLUTION: A microfluidic device in which at least two or more plate-like members are joined includes a port for supplying or discharging liquid, and a flow path formed inside the microfluidic device and communicating with the port, where the flow path has a tubular shape constituted by three or more inner wall surfaces, and a cross section of the flow path includes at least three or more corner portions having an angle being an acute angle.SELECTED DRAWING: Figure 5

Description

[Technical Field]

[0001] The present invention relates to microfluidic devices. [Background technology]

[0002] Conventional microfluidic devices are provided with tiny flow channels (also called microchannels) used for cell culture, etc., and the cross section of the flow channel is rectangular with right-angled corners (for example, Patent Documents 1 and 2). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent No. 7081605 [Patent Document 2] Japanese Patent Application Publication No. 2023-54495 Summary of the Invention [Problem to be solved by the invention]

[0004] However, when a microchannel has a rectangular cross section with four right-angled corners, there is a problem that when a liquid such as a cell culture medium is injected into the microchannel, the liquid has difficulty entering the microchannel due to the influence of the surface energy of the channel and the surface tension of the liquid.In particular, when the microchannel is cut perpendicular to the flow direction, the length of the short side of the channel cross section is less than 1 mm, or even 0.5 mm or less, the problem of the liquid not being able to enter the microchannel is evident.

[0005] In view of the above-mentioned problems, an object of the present invention is to provide a microfluidic device that allows a liquid, such as a cell culture medium, to easily enter a microchannel when the liquid is injected into the microchannel. [Means for solving the problem]

[0006] The microfluidic device according to the present invention is a microfluidic device in which at least two or more plate-like members are joined together, a port for supplying or discharging a liquid; a channel formed inside the microfluidic device and communicating with the port; The flow path is tubular and has three or more inner wall surfaces, The cross section of the flow path has at least three or more acute corners.

[0007] According to this configuration, the acute angled corners induce a stronger capillary phenomenon in the liquid injected into the flow channel than an obtuse angle of 90° or more, so the liquid easily enters the flow channel.

[0008] Furthermore, in the microfluidic device according to the present invention, At least one of the inner wall surfaces of the flow path is curved or bent and protrudes toward the inside of the flow path, The angle formed between the protruding inner wall surface and another inner wall surface adjacent to the protruding inner wall surface is an acute angle.

[0009] With this configuration, the acute angle between the protruding inner wall surface and another inner wall surface adjacent to the protruding inner wall surface causes capillary action when liquid is injected into the flow path, making it easier for the liquid to enter the flow path.

[0010] Furthermore, in the microfluidic device according to the present invention, a contact angle between a liquid injected into the channel and the inner wall surface may be less than 90°.

[0011] If the contact angle between the liquid to be injected into the flow channel and the inner wall surface is less than 90°, it becomes easier to inject the liquid into the flow channel.

[0012] In addition, in the microfluidic device according to the present invention, the plate-like member may be made of at least one material selected from polymethyl methacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC), cycloolefin polymer (COP), polystyrene (PS), silicone, and acrylic.

[0013] According to this configuration, the holes and recesses that form the flow paths can be easily formed in the plate-like member by injection molding.

[0014] In the microfluidic device according to the present invention, the length of the shortest side of the cross section of the flow channel is set to be 1 μm or more and 1000 μm or less.

[0015] If the length of the shortest side of the cross section of the flow channel is less than 1 μm, it is difficult to manufacture and control the angle of the acute angle, and the flow channel itself may be crushed. If it is 1 μm or more, it is easy to form the flow channel by injection molding, post-processing using a mold to transfer, cutting, etching, etc. If it is 1000 μm or less, it is easy to inject liquid into the flow channel. [Brief explanation of the drawings]

[0016] [Figure 1] 1 is a perspective view of a microfluidic device according to an embodiment of the present invention; [Figure 2] 1 is a plan view of a microfluidic device according to an embodiment of the present invention; [Figure 3] Cross-sectional view of the microfluidic device shown in Figure 2, taken along line III-III [Figure 4] Cross-sectional view of the microfluidic device shown in Figure 2, taken along line IV-IV. [Figure 5] Enlarged view of the V region in Figure 4 [Figure 6] 1 is a perspective view showing the first substrate and the second substrate immediately before they are bonded to each other; [Figure 7] 1 is a cross-sectional view of a channel of a microfluidic device according to another embodiment. [Figure 8] 1 is a cross-sectional view of a channel of a microfluidic device according to another embodiment. [Figure 9] 1 is a cross-sectional view of a channel of a microfluidic device according to another embodiment. [Figure 10] 1 is a cross-sectional view of a channel of a microfluidic device according to another embodiment. [Figure 11] 1 is a cross-sectional view of a channel of a microfluidic device according to another embodiment. [Figure 12] 1 is a cross-sectional view of a channel of a microfluidic device according to another embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0017] The microfluidic device according to the present invention will be described with reference to the drawings. Note that the drawings disclosed in this specification are merely schematic illustrations. That is, the dimensional ratios in the drawings do not necessarily match the actual dimensional ratios, and the dimensional ratios between the drawings do not necessarily match.

[0018] Fig. 1 is a perspective view of a microfluidic device 1 according to this embodiment, and Fig. 2 is a plan view of the microfluidic device 1 according to this embodiment. Fig. 3 is a cross-sectional view of the microfluidic device 1 shown in Fig. 2 taken along line III-III, and Fig. 4 is a cross-sectional view of the microfluidic device 1 shown in Fig. 2 taken along line IV-IV. Fig. 5 is an enlarged view of region V in Fig. 4.

[0019] The microfluidic device 1 is manufactured by bonding at least two or more plate-like members. For example, the microfluidic device 1 is manufactured by bonding two plate-like members, a first substrate 10 and a second substrate 20.

[0020] 3, the microfluidic device 1 is formed by stacking and bonding one main surface 20a of a second substrate 20 onto one main surface 10a of a first substrate 10 so that they are in partial contact with each other. The main surface refers to a surface that is much larger in area than the other surfaces constituting the substrates 10 and 20. The substrates 10 and 20 each have two main surfaces that are arranged opposite each other.

[0021] The main surface 20a of the second substrate 20, which is in partial contact with the first substrate 10, has a recess 20c (described later). The other main surface 20b of the second substrate 20 is located on the opposite side to the first substrate 10 and has openings for ports 3 and 4 (described later).

[0022] In the following description, when the first substrate 10 and the second substrate 20 are bonded together, the XYZ coordinate system will be referred to as appropriate, in which a plane parallel to the main surfaces 10a, 10b of the first substrate 10 and the main surfaces 20a, 20b of the second substrate 20 is defined as the XY plane, and the direction perpendicular to this XY plane is defined as the Z direction.

[0023] Furthermore, in this specification, when expressing a direction, if a distinction is made between positive and negative directions, the direction is described with a positive or negative sign, such as "+X direction" and "-X direction." Furthermore, when a direction is expressed without distinguishing between positive and negative directions, it is simply described as "X direction." In other words, in this specification, when simply referring to "X direction," both the "+X direction" and the "-X direction" are included. The same applies to the Y direction and the Z direction. Note that the microfluidic device 1 is usually used with the Z direction as the up-down direction, and the -Z direction corresponds to the upward direction.

[0024] The first substrate 10 and the second substrate 20 each have a main surface of the same shape. In the microfluidic device 1 of this embodiment, the first substrate 10 and the second substrate 20 are rectangular when viewed in the Z direction. The second substrate 20 is thicker than the first substrate 10. The thickness of the first substrate 10 is, for example, 0.1 to 3 mm, and the thickness of the second substrate 20 is, for example, 1 to 10 mm.

[0025] 1, the microfluidic device 1 includes a device body 2 having a substantially rectangular parallelepiped shape. The microfluidic device 1 includes a first port 3 and a second port 4 that open on the upper surface (main surface 20b) of the device body 2. The first port 3 and the second port 4 are arranged side by side in the X direction. The first port 3 and the second port 4 are also arranged spaced apart from each other.

[0026] The first port 3 and the second port 4 are both cylindrical cavities extending in the Z direction. The diameters of the first port 3 and the second port 4 are the same, for example, 0.5 mm to 5 mm. However, the diameters of the first port 3 and the second port 4 do not have to be the same.

[0027] The first port 3 and the second port 4 are used to supply or discharge a liquid to or from the microfluidic device 1. For example, a liquid can be supplied from the first port 3 and discharged from the second port 4.

[0028] The microfluidic device 1 is provided with a flow channel 5 formed inside the device body 2 and communicating with a first port 3 and a second port 4. The flow channel 5 is formed by the main surface 10a of the first substrate 10 and the recess 20c of the second substrate 20 when the first substrate 10 and the second substrate 20 are bonded together.

[0029] Both ends of the flow channel 5 are connected to the bottoms of the first port 3 and the second port 4, respectively. The first port 3 is connected to the end of the flow channel 5 on the −X direction side, and extends from the main surface 20a toward the main surface 20b of the second substrate 20, penetrating the second substrate 20. The second port 4 is connected to the end of the flow channel 5 on the +X direction side, and extends from the main surface 20a toward the main surface 20b of the second substrate 20, penetrating the second substrate 20.

[0030] The flow path 5 is tubular and is made up of three or more inner wall surfaces. As shown in Fig. 5, the flow path 5 of this embodiment is tubular and is made up of four inner wall surfaces 51 to 54. The cross section of the flow path 5 is substantially rectangular.

[0031] At least one of the four inner wall surfaces 51 to 54 is a protruding surface that is curved or bent and protrudes toward the inside of the flow channel 5. As shown in FIG. 5, all of the four inner wall surfaces 51 to 54 of this embodiment are curved and protrude toward the inside of the flow channel 5.

[0032] The flow path 5 has four corners 55-58 formed by the four inner wall surfaces 51-54. The angle formed by a protruding inner wall surface 51-54 and another inner wall surface 51-54 adjacent to the protruding inner wall surface 51-54 is an acute angle. In this embodiment, since all the inner wall surfaces 51-54 are protruding surfaces, the angles of the corners 55-58 are all acute angles, as shown in FIG. 5.

[0033] Although the angles of the four corners 55 to 58 in this embodiment are all acute angles, the cross section of the flow path 5 may have at least three or more corners 55 to 58 that are acute angles.

[0034] Since the cross section of the flow channel 5 has at least three or more acute corners 55-58, the acute corners 55-58 induce a stronger capillary phenomenon in the liquid injected into the flow channel 5 than obtuse angles of 90° or more, making it easier for the liquid to enter the flow channel 5.

[0035] Furthermore, the contact angle between the liquid (e.g., culture solution) injected into the flow channel 5 and the inner wall surfaces 51 to 54 is preferably less than 90°. If the contact angle is less than 90°, it becomes easier to inject the liquid into the flow channel 5. The contact angle between the liquid injected into the flow channel 5 and the inner wall surfaces 51 to 54 is more preferably less than 80°, and particularly preferably less than 60°.

[0036] Furthermore, the length of the shortest side of the cross section of the flow channel 5 is preferably 1 μm or more and 1000 μm or less. In this embodiment, the length of the cross section of the inner wall surface 51 and the inner wall surface 53 is the shortest, and the length of the cross section of the inner wall surface 51 and the inner wall surface 53 is preferably 1 μm or more and 1000 μm or less. If the length of the shortest side of the cross section of the flow channel 5 is less than 1 μm, it is difficult to manufacture an acute angle and control the angle, and the flow channel itself may be crushed. If it is 1 μm or more, it is easy to form the flow channel by injection molding, post-processing by transferring using a mold, cutting, etching, or the like. If it is 1000 μm or less, it is easy to inject liquid into the flow channel.

[0037] Furthermore, the deflection of the inner wall surfaces 51 to 54 is preferably 0.9% or more and 9% or less. If the deflection of the inner wall surfaces 51 to 54 is less than 0.9%, the capillary force becomes less effective (smaller), making it difficult for liquid to enter the flow path. If the deflection is greater than 9%, the desired flow path shape cannot be obtained, resulting in poor cell culture and cell observation.

[0038] Furthermore, the bending angle of the inner wall surfaces 51 to 54 is preferably 1° or more and 10° or less. If the bending angle of the inner wall surfaces 51 to 54 is smaller than 1°, the capillary force becomes less effective (smaller), making it difficult for liquid to enter the flow path. If the bending angle is larger than 10°, the flow path shape cannot be obtained, and cell culture and cell observation become difficult.

[0039] Next, the following describes an example of a method for manufacturing the microfluidic device 1. Figure 6 is a perspective view showing the first substrate 10 and the second substrate 20 immediately before bonding the two substrates 10 and 20 to each other.

[0040] (Substrate preparation process) First, a first substrate 10 and a second substrate 20 are prepared, which constitute the microfluidic device 1. At this stage, the first substrate 10 and the second substrate 20 are, for example, rectangular plate-shaped members.

[0041] The first substrate 10 and the second substrate 20 are preferably made of a substantially non-porous material. Here, "substantially non-porous" refers to a state in which the apparent surface area of ​​the substrate is close to its actual surface area. Examples of materials that form such non-porous bodies include inorganic materials such as glass and silicon, and resin materials such as polymethyl methacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC), cycloolefin polymer (COP), polystyrene (PS), silicone, and acrylic. Two or more of these resin materials may be combined. The materials used for the first substrate 10 and the second substrate 20 may also be different.

[0042] (Shape processing of second substrate 20) The first through-hole 20d, the second through-hole 20e, and the recess 20c are formed in the second substrate 20 in regions where the first port 3, the second port 4, and the flow path 5 are to be formed, respectively, by injection molding, cutting, or other methods. The first through-hole 20d, the second through-hole 20e, and the recess 20c can be formed in the second substrate 20 by, for example, injection molding, cutting, or other methods, and the most appropriate method may be selected depending on the material constituting the substrate. For example, by forming the second substrate 20 from a resin material such as polymethyl methacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC), cycloolefin polymer (COP), polystyrene (PS), silicone, or acrylic, as described above, the first through-hole 20d, the second through-hole 20e, and the recess 20c can be easily formed by injection molding.

[0043] The recess 20c is formed on the main surface 20a so as to extend in the X direction. When the first substrate 10 and the second substrate 20 are bonded together, the recess 20c forms a hollow flow path 5 between the first substrate 10 and the recess 20c.

[0044] The recess 20c is, for example, a slit-like shape that has a constant width and depth and extends in the X direction. The cross section of the recess 20c is rectangular.

[0045] The width of the recess 20c in the Y direction is, for example, 10 μm to 1000 μm, the depth of the recess 20c in the Z direction is, for example, 1 μm to 1000 μm, and the length of the recess 20c in the X direction is, for example, 1 mm to 30 mm.

[0046] The first through hole 20d is connected to the end of the recess 20c on the -X direction side, extends from the main surface 20a toward the main surface 20b of the second substrate 20, and is formed to penetrate the second substrate 20. The second through hole 20e is connected to the end of the recess 20c on the +X direction side, extends from the main surface 20a toward the main surface 20b of the second substrate 20, and is formed to penetrate the second substrate 20. The first through hole 20d and the second through hole 20e have the same diameter, for example, not less than 0.5 mm and not more than 5 mm.

[0047] (Joining process) The first substrate 10 and second substrate 20 thus shaped are bonded together to obtain the microfluidic device 1 shown in Fig. 1. Bonding methods that can be used include bonding using surface modification using light or plasma, thermal bonding, adhesion using an adhesive, and bonding using a solvent. An example of a bonding method is as follows.

[0048] First, a surface activation process is performed on the bonding surfaces of the first substrate 10 and the second substrate 20. As a method for the surface activation process, a method of irradiating ultraviolet light can be used. Specifically, this is performed by irradiating vacuum ultraviolet light (VUV) with a wavelength of 200 nm or less from an ultraviolet light source. Suitable ultraviolet light sources include a Xe excimer lamp with a peak wavelength of around 172 nm, a low-pressure mercury lamp with an emission line at 185 nm, and a deuterium lamp with an emission line in the wavelength range of 120 to 200 nm. The illuminance of the vacuum ultraviolet light is, for example, 10 to 500 mW / cm. 2 The irradiation time is set appropriately depending on the materials from which the first substrate 10 and the second substrate 20 are made, but is, for example, 0.1 to 60 seconds.

[0049] Next, the bonding surfaces of the first substrate 10 and the second substrate 20 that have been subjected to the surface activation treatment are brought into contact with each other and pressed together using a press or the like. This process is carried out in a heated environment as necessary to strengthen the bond. In the bonding process, bonding conditions such as the heating temperature and pressing force are set depending on the constituent materials of the first substrate 10 and the second substrate 20. Specific conditions include a temperature during pressing of, for example, 40 to 150°C, and a pressing force for bonding of, for example, 0.1 to 10 MPa. This bonding process is preferably carried out in a state where the surface activation state of the bonding surfaces of the first substrate 10 and the second substrate 20 is maintained. From this perspective, it is recommended to carry out the bonding process within, for example, 10 minutes after completion of ultraviolet irradiation.

[0050] After the first substrate 10 and the second substrate 20 are pressed, they may be heated for a further predetermined time as necessary. As a specific example, after the first substrate 10 and the second substrate 20 are kept pressed for a predetermined time, the pressed state may be released and the temperature may be raised to a predetermined temperature, and the temperature may be maintained until the desired bonding state is achieved.

[0051] As described above, the cross section of the recess 20c formed in the second substrate 20 is rectangular. When the first substrate 10 and the second substrate 20 are heated and pressed together under predetermined conditions to form the recess 20c having such a rectangular cross section, the side walls and bottom wall of the recess 20c deform toward the inside of the recess 20c. At the same time, the main surface 10a of the first substrate 10 facing the recess 20c deforms toward the recess 20c. As a result, the flow channel 5 is formed such that the four inner wall surfaces 51 to 54 are curved to form protruding surfaces that protrude toward the inside of the flow channel 5, as shown in FIG.

[0052] After that, a cooling step is performed, and the microfluidic device 1 in which the second substrate 20 is in partial contact with the upper surface of the first substrate 10 is obtained.

[0053] Although the embodiments of the present invention have been described above with reference to the drawings, the specific configurations should not be considered to be limited to these embodiments. The scope of the present invention is defined not only by the description of the above embodiments but also by the claims, and further includes all modifications within the meaning and scope of the claims.

[0054] The structures employed in the above-described embodiments can be employed in any other embodiment. The specific configurations of the components are not limited to the above-described embodiments, and various modifications are possible within the scope of the present invention.

[0055] (1) In the above embodiment, the cross section of the flow channel 5 has a substantially rectangular shape, but is not limited to this. For example, the cross section of the flow channel 5 may have a substantially trapezoidal shape as shown in FIG.

[0056] (2) In the above embodiment, all four inner wall surfaces 51 to 54 are curved and protrude toward the inside of the flow channel 5, but this is not limiting. For example, as shown in FIG. 8, two inner wall surfaces 51 and 53 may be curved and protrude toward the inside of the flow channel 5, and two inner wall surfaces 52 and 54 may be flat. Such inner wall surfaces 51 to 54 are formed by appropriately adjusting the pressure and time applied when bonding the first substrate 10 and the second substrate 20, the heating time, and the like. Making the upper and lower inner wall surfaces 52 and 54 parallel and flat surfaces makes it easier to observe the inside of the flow channel 5 with a microscope after cell culture.

[0057] (3) Furthermore, as shown in Fig. 9, all four inner wall surfaces 51 to 54 may be bent and protrude toward the inside of the flow path 5. Such inner wall surfaces 51 to 54 may be formed by cutting work in addition to injection molding.

[0058] (4) In the above embodiment, the microfluidic device 1 is manufactured by bonding two plate-like members, the first substrate 10 and the second substrate 20, but this is not limiting. The microfluidic device 1 may also be manufactured by bonding three or more plate-like members, as shown in FIG.

[0059] (5) In the above embodiment, the first substrate 10 and the second substrate 20 are heated and pressed together to form the flow path 5 having the inner wall surfaces 51-54 that are curved and protrude toward the inside of the flow path 5, but this is not limiting. For example, as shown in Fig. 11, when the flow path 5 is formed by injection molding, the first substrate 10 and the second substrate 20 each having a convex curved surface and the third substrate 30 having a through hole formed in a portion corresponding to the side surface of the flow path 5 may be prepared, and these three plate-like members may be joined together to form the flow path 5 having the inner wall surfaces 52, 54 that are curved and protrude toward the inside of the flow path 5.

[0060] (6) Also, for example, a flat first substrate 10 and a flat second substrate 20, and a third substrate 30 having a through hole formed in a portion corresponding to the side of the flow channel 5 are prepared. As shown in Fig. 12, by providing an inclined portion such as a C-surface or an R-surface by cutting the upper and lower opening edges of the through hole in the third substrate 30, it is possible to form an acute corner when the third substrate 30 is joined to the first substrate 10 and the second substrate 20. [Explanation of symbols]

[0061] 1: Microfluidic device 2: Device itself 3: First port 4: Second port 5: Flow path 10: First board 10a: Main surface 10b: Main surface 20: Second board 20a: Main surface 20b: Main surface 20c: Recess 20d: 1st through hole 20e: 2nd through hole 30: Third board 51: Inner wall surface 52: Inner wall surface 53: Inner wall surface 54: Inner wall surface 55: Corner 56: Corner 57: Corner 58: Corner

Claims

1. A microfluidic device in which at least two or more plate-like members are joined, a port for supplying or discharging a liquid; a channel formed inside the microfluidic device and communicating with the port; The flow path is tubular and has three or more inner wall surfaces, A microfluidic device, wherein a cross section of the flow channel has at least three or more corners that are acute angles.

2. At least one of the inner wall surfaces of the flow path is curved or bent and protrudes toward the inside of the flow path, The microfluidic device according to claim 1 , wherein an angle formed between the protruding inner wall surface and another inner wall surface adjacent to the protruding inner wall surface is an acute angle.

3. The microfluidic device according to claim 1 , wherein a contact angle between a liquid injected into the channel and the inner wall surface is less than 90°.

4. 3. The microfluidic device according to claim 1, wherein the plate-like member is made of at least one material selected from polymethyl methacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC), cycloolefin polymer (COP), polystyrene (PS), silicone, and acrylic.

5. 3. The microfluidic device according to claim 1, wherein the length of the shortest side of the cross section of the flow channel is 1 μm or more and 1000 μm or less.

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