JP6627759B2 - Method for manufacturing molding die, method for manufacturing micromixer, and method for manufacturing microfluidic chip - Google Patents

Description

  The present invention relates to a molding die and a method of manufacturing the same, and more particularly to a technique capable of suppressing the generation of liquid residues in a micromixer or a microfluidic chip including the same, and the generation of scratches and dust due to mold release. .

BACKGROUND ART Conventionally, a microfluidic chip that supplies a liquid such as test blood to a fine channel and mixes and reacts the liquid has been known (see Patent Document 1).
In the technique of Patent Literature 1, the arrangement of the liquid injection port (30 in) of the mixing tank (30) and the shape of the bottom (30 bt) of the mixing tank are devised to mix and mix liquids in the mixing tank as a micromixer. Attempts have been made to reduce the residue of liquid in the tank (see FIGS. 5 to 8, FIGS. 11 to 16, and the like). Patent Literature 1 suggests that in order to promote these, it is better to apply a water-repellent treatment such as a fluorine coating to the surface of the inner wall of the mixing tank (see paragraph 0081 and the like).
Patent Document 2 also discloses a technique for reducing liquid residues. In Patent Document 2, a target portion (a portion near the extraction port 302b) is coated with a well-known water-repellent material, and a water contact angle and a surface roughness of an inner surface thereof are controlled within a certain range to reduce a liquid residue. (See paragraphs 0046, 0055 to 0056, etc.).
However, the use of the water-repellent coating technique as in Patent Documents 1 and 2 is not sufficient as a technique for reducing liquid residues because the coating film can be peeled off due to aging. .

On the other hand, as described in Patent Document 1, the shape of a mixing tank for mixing a liquid such as a test liquid is such that the liquid does not adhere to the inner wall surface and no liquid remains, that is, the inner wall surface is horizontal. When molding a mixing tank having a vertical surface perpendicular to the above, it is necessary to use a mold having a convex portion provided upright to a cavity (molding space). As the processing of the vertical surface, a method of processing using a lathe is generally used. However, in the case of a mixing tank shape as described in Patent Literature 1, the bottom of the mixing tank is not axially symmetric, so that such a die processing is performed. As a method, machining center processing using an R1 ball end cutter can be considered.
Although Patent Document 1 does not particularly mention the processing method, for example, when the processing pitch is set to 0.05 mm, the side of the mold is theoretically 0 at the intersection of the arc shapes of the cutters. Processing traces are formed at intervals of 0.05 mm, but intervals of 0.05 mm or more may be formed due to variations in processing accuracy. Also, depending on the shape of the cutting edge of the ball end cutter to be used, even if the height is the minimum, a “peak (concavity and convexity)” having a height of 0.0003 mm is formed. When an attempt is made to mold a mixing tank using a mold formed by such processing, the irregularities formed during the processing of the mold are transferred to the inner wall surface of the resin molded article, and the irregularities are formed when the mold is released. And the surface is scratched, and dust is likely to be generated. Further, even if the machining program of the machining center is the same, it is difficult to reproduce the above-mentioned theoretical unevenness due to the degree of wear of the cutter, and unevenness of the mold occurs.
Even if the technology described in Patent Document 2, that is, a technology in which a blasted mold surface is transferred and the surface roughness of a molded product is controlled within a certain range, Patent Document 2 discloses such a mold. Since the target portion to be transferred to the surface (the portion near the extraction opening 302b) has a tapered shape (see paragraph 0058 and the like), the inner wall surface of the target portion is inclined, and scratches and dust are generated when the mold is released. Is not assumed and such technology cannot be diverted as it is.

Japanese Patent No. 5029669 JP 2005-353030 A

  Accordingly, a main object of the present invention is a micromixer having a vertical surface or a microfluidic chip including the same, which can suppress generation of scratches and dust due to generation of liquid residue and release from the mold. An object of the present invention is to provide a mold capable of manufacturing a microfluidic chip including the same and a method for manufacturing the same.

In order to solve the above problems, according to one embodiment of the present invention,
A molding die for molding a micromixer having a vertical surface or a microfluidic chip including the same, comprising a convex portion for forming the micromixer, wherein the convex portion has a surface roughness of 0. In a method for producing a molding die having a size of from 01 to 5 μm,
A step of subjecting the base material to machining center processing using a ball end cutter, and forming a convex precursor for forming a micromixer,
A step of subjecting the surface of the projection precursor to a mirror polishing treatment, a YEPCO treatment or a blast treatment to make the surface roughness of the surface 0.01 to 5 μm,
Equipped with a,
In the step of forming the convex part precursor, the convex part precursor, with respect to its central axis, forming mold manufacturing method, wherein to Rukoto asymmetric shape is provided.

  ADVANTAGE OF THE INVENTION According to this invention, even if it does not perform a water-repellent coating, the micromixer which can suppress generation | occurrence | production of the residue of a liquid and generation | occurrence | production of the damage | wound and dust accompanying mold release, or the microfluidic chip which has this can be manufactured. .

FIG. 2 is a schematic cross-sectional view illustrating a schematic configuration of a microfluidic chip. FIG. 3 is a diagram illustrating the movement of a test solution in a microfluidic chip. FIG. 3 is a diagram illustrating the movement of a test solution in a microfluidic chip. FIG. 3 is a diagram illustrating the movement of a test solution in a microfluidic chip. It is a cross section showing the structure of a mixing tank. It is a plane schematic diagram which shows the structure of a mixing tank. It is a figure for explaining the structure of a mixing tank. It is a figure for explaining convection of a test liquid in a mixing tank. It is a figure for explaining the structure of the mixing vessel concerning a comparative example. It is a figure for explaining convection of a test liquid in a mixing vessel concerning a comparative example. It is a figure which shows the behavior of the test liquid in a mixing tank typically. It is a figure which shows the behavior of the test liquid in a mixing tank typically. It is a figure which shows the behavior of the test liquid in a mixing tank typically. It is a figure which shows the behavior of the test liquid in a mixing tank typically. It is a figure which shows the behavior of the test liquid in a mixing tank typically. It is a figure which shows the behavior of the test liquid in a mixing tank typically. It is a figure showing the schematic structure of an injection molding device. FIG. 3 is a diagram illustrating a state in which an ejector mechanism of the injection molding device is operated. It is a figure showing the schematic structure of the liquid sending device used for a liquid sending test.

  Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings.

<(1) Schematic configuration of microfluidic chip>
FIG. 1 is a schematic sectional view showing a schematic configuration of the microfluidic chip 1. In FIG. 1 and other figures subsequent to FIG. 1, three XYZ axes orthogonal to each other are given for the purpose of clarifying the azimuth relationship.

  The microfluidic chip 1 is, for example, a device that supplies a liquid to a fine channel having a width and a depth of several μm to several hundred μm and performs mixing and reaction of the liquid based on the behavior of molecules and particles constituting the liquid. is there. The microfluidic chip 1 includes a block-shaped main body 10, a fine flow path 20 extending linearly in the main body 10, and a mixing for promoting the mixing of the test liquid flowing through the fine flow path 20. A tank 30, an injection / discharge port 40 for injecting and discharging a test liquid and air into and from the fine flow path 20, and a reaction unit 50 provided in the fine flow path 20 so that its reaction surface is exposed.

The main body 10 is made of a low-cost disposable resin, and specifically, a thermoplastic resin is used. As the thermoplastic resin, for example, polycarbonate, polymethyl methacrylate, polystyrene, polyacrylonitrile, polyvinyl chloride, polyethylene terephthalate, nylon 6, nylon 66, polyvinyl acetate, polyvinylidene chloride, polypropylene, polypropylene, polyisoprene, polyethylene, poly It is preferable to use dimethylsiloxane, cyclic polyolefin and the like, and among these, it is particularly preferable to use polymethyl methacrylate and cyclic polyolefin.
The main body 10 has, for example, a size of about 50 mm in width, about 50 mm in depth, and about 10 mm in height. Further, a plurality of parts constituting the main body 10 are separately formed by cutting or injection molding, and the plurality of parts are joined with an adhesive or the like, whereby the main body 10 is completed.

  The fine channel 20 has a size of, for example, a width of about 1 to 3 mm and a height of about several tens of μm to 1 mm, but is not limited thereto. The flow path length is not particularly limited. However, when the flow of the test liquid in the fine flow path 20 becomes laminar depending on the flow path conditions (size and the like), the present invention works more effectively, Bring effect.

  The mixing tank 30 is provided so as to communicate with one end of the fine channel 20, and functions as a minute mixer (micromixer) for mixing and stirring the test solution injected into the mixing tank 30. Further, the mixing tank 30 has a volume equal to or more than a specified amount of the test liquid. The mixing tank 30 has a structure that facilitates mixing and stirring of the test liquid, as described later.

  The injection / discharge port 40 is provided so as to communicate with the other end of the fine channel 20. Further, a supply source of the test liquid and a pump for injecting and discharging the test liquid are connected to the injection / discharge port 40. In addition, a pump for injecting the test liquid from the injection / discharge port 40 and discharging the test liquid from the injection / discharge port 40 may be connected to the mixing tank 30.

  The reaction unit 50 is provided at a lower position of the fine flow channel 20 at an intermediate position between portions of the fine flow channel 20 where the mixing tank 30 and the injection / exhaust port 40 communicate with each other. Then, in the reaction section 50, the biochemical substance diffused into the test liquid passing near the reaction section 50 reacts. Examples of the test solution include plasma obtained by centrifuging blood collected from a living body, and biochemical substances contained in the test solution include various antigens and the like present in blood. Is mentioned. In addition, examples of the reactant constituting the reaction section 50 include an antibody capable of specifically reacting with the antigen.

<(2) Rough flow of test liquid in microfluidic chip>
FIG. 2 to FIG. 4 are diagrams for explaining a rough flow of the test solution Ex in the microfluidic chip 1.

  In the test, first, as shown in FIG. 2, the test liquid Ex is injected into the microchannel 20 from the outside of the microfluidic chip 1 via the injection port 40, and the test liquid Ex is injected into the microchannel 20. It is injected into the mixing tank 30 through 20. Then, as shown in FIG. 3, the test liquid Ex is temporarily stored in the mixing tank 30. Next, as shown in FIG. 4, the test liquid Ex stored in the mixing tank 30 is discharged from the injection / discharge port 40 to the outside of the microfluidic chip 1 through the fine flow path 20.

  The test liquid Ex reacts in the reaction section 50 during a period from the injection of the test liquid Ex to the microfluidic chip 1 to the discharge thereof. Specifically, the test liquid Ex reacts in the reaction unit 50 when the test liquid Ex moves from the injection / discharge port 40 to the mixing tank 30 and when the test liquid Ex moves from the mixing tank 30 to the injection / discharge port 40. .

  Here, when the flow of the test liquid Ex in the fine flow path 20 is a laminar flow, the concentration of the biochemical substance in the vicinity of the reaction part 50 in the test liquid Ex decreases due to the reaction with the reaction part 50. For this reason, when the test liquid Ex moves from the injection / exhaust port 40 to the mixing tank 30, the test liquid Ex reacts with the reaction unit 50 so that the concentration of the biochemical substance flowing in the upper part of the fine channel 20 becomes relatively high. (High-concentration test solution) and a test solution (low-concentration test solution) in which the concentration of the biochemical substance flowing in the lower part of the microchannel 20 is relatively low.

  Since the flow of the test liquid Ex in the fine flow path 20 is laminar, unless the mixing and stirring of the high-concentration test liquid and the low-concentration test liquid is performed in portions other than the fine flow path 20, the fine flow path When the test liquid Ex is discharged from the inlet / outlet 40 through the inlet 20, the reaction between the test liquid Ex and the reaction unit 50 hardly progresses. However, in the microfluidic chip 1 according to the present embodiment, the mixing tank 30 has a structure in which the test liquid Ex is easily mixed and stirred, as described later.

  For this reason, when the test liquid Ex as a mixed liquid generated by mixing the high-concentration test liquid and the low-concentration test liquid in the mixing tank 30 is discharged from the mixing tank 30, It reacts with the reaction part 50 provided near the lower inner wall surface.

  After the test solution Ex is discharged from the microfluidic chip 1, for example, by detecting externally a change in the optical characteristics of the solid-phased surface of the reaction unit 50, the immune reaction between the antigen and the antibody is measured. You. For this detection, an optical device may be used, or visual observation by the naked eye may be used. If the material of the main body 10 is made of a transparent resin or the like, observation from the outside is easy.

<(3) Structure of mixing tank>
FIG. 5 is a schematic cross-sectional view showing the structure of the mixing tank 30, and FIG. 6 is a schematic top view showing the structure of the mixing tank 30. FIG. 5 shows a cross section (XZ cross section) of the mixing tank 30 parallel to the XZ plane, and FIG. 6 shows a view of the mixing tank 30 as viewed from the + Z direction.

  As shown in FIG. 5 and FIG. 6, the mixing tank 30 is a tank part whose upper part (+ Z direction) is open and in which a liquid inlet 30in is provided in a bottom part 30bt.

  The space (internal space area) 30sp surrounded by the inner wall of the mixing tank 30 is formed such that the shape of a cross section (XY cross section) parallel to a plane perpendicular to the Z axis except for the vicinity of the liquid injection port 30in is substantially circular. It is formed. From another viewpoint, the internal space region 30sp has a shape that is rotationally symmetric in all directions around an axis L1 parallel to the Z axis except for the vicinity of the liquid inlet 30in. In other words, the axis L1 is a straight line that passes through the position of the center of gravity of each XY cross section of the internal space region 30sp in the vertical direction (the direction of the Z axis) except for the vicinity of the liquid inlet 30in. Hereinafter, the axis L1 is also referred to as a line (center line) indicating the center of the mixing tank 30.

  When the positions of the centers of gravity of the plurality of XY sections in the internal space area 30sp do not lie on one straight line, the positions of the centers of gravity of the plurality of XY sections are approximated from the positions of the centers of gravity of the plurality of XY sections. A straight line may be obtained as the center line L1.

  Further, a side surface (side wall portion) 30sw of the inner wall of the mixing tank 30 forming the internal space region 30sp forms a wall surface substantially parallel to the Z axis.

  The liquid injection port 30in is provided in the bottom 30bt of the mixing tank 30 at a position shifted in the -X direction from the axis L1. The liquid inlet 30in communicates with the fine channel 20. Therefore, the test liquid Ex is injected from the fine channel 20 into the internal space region 30sp via the liquid injection port 30in. Since the flow path connecting the liquid injection port 30in and the fine flow path 20 extends in the direction along the Z axis, the flow of the test liquid Ex injected from the liquid injection port 30in into the internal space region 30sp. The direction is the + Z direction. The liquid inlet 30 in also plays a role of discharging the test liquid Ex stored in the mixing tank 30 toward the fine flow path 20.

  The bottom portion 30bt is a portion where the XY cross section of the internal space region 30sp becomes narrower as going downward (-Z direction). Specifically, the closer to the liquid inlet 30in, the narrower the XY cross section of the internal space region 30sp of the bottom 30bt. The liquid inlet 30in is provided at a position shifted from the center of the bottom 30bt.

  Here, the center of the bottom portion 30bt refers to a portion of the bottom portion 30bt through which a straight line passes vertically through the center of gravity of the plane area where the bottom portion 30bt is projected on the XY plane (in the direction of the Z axis). In addition, the center of the bottom 30bt may be a portion through which an approximate straight line that passes through the center of gravity of a plurality of XY cross sections of the space region formed by the bottom 30bt in the vertical direction (Z-axis direction) in the internal space region 30sp. . Further, here, the center of the bottom portion 30bt is substantially the same as the portion through which the axis L1 passes.

  The bottom 30bt has a liquid inlet 30in, a liquid reservoir 30ph, and an inclined portion 30tp. The liquid reservoir 30ph is a portion that forms a substantially semi-spherical space that is convex downward. Further, the inclined portion 30tp has a substantially constant inclination from a portion near the point where the axis L1 passes through toward the liquid inlet 30in.

  As shown in FIG. 6, when viewed from above (+ Z direction), the inclined portion 30tp has a fan-shaped surface (shaded portion in FIG. 6) that requires the liquid inlet 30in. It is composed. That is, the inclined portion 30tp tapers toward the liquid inlet 30in. Further, the inclined portion 30tp has a form in which a constant inclination is maintained in any direction with respect to the liquid injection port 30in. Due to the presence of the inclined portion 30tp, the discharge of the test liquid Ex from the liquid inlet 30in is promoted, so that the residual test liquid Ex in the mixing tank 30 is suppressed. If the liquid does not easily remain in the mixing tank 30, waste of the test liquid Ex is also suppressed.

  Also, regardless of the direction from the liquid inlet 30in to the inclined portion 30tp, the angle formed by the inclined portion 30tp with the horizontal plane at the portion approaching the liquid reservoir 30ph changes rapidly. For this reason, any of the curved surfaces of the inclined portion 30tp and the liquid reservoir 30ph is discontinuous at the boundary between the inclined portion 30tp and the liquid reservoir 30ph, and a portion corresponding to a gently protruding convex portion is formed near the boundary. You.

  FIG. 7 is a view for explaining the structure of the mixing tank 30 from another viewpoint. FIG. 7 shows a cross section (XZ cross section) of the mixing tank 30 parallel to the XZ plane, as in FIG. A line (virtual line) L2 extending virtually through the center of the liquid inlet 30in and upward (in the + Z direction) is provided.

  As shown in FIG. 7, for the same Z coordinate, the distance D1 from the imaginary line L2 to the inner wall surface of the mixing tank 30 in the −X direction and the distance from the imaginary line L2 to the inner wall surface of the mixing tank 30 in the + X direction. Is different from D2. In other words, in the XY cross section along the horizontal direction of the internal space region 30sp, the distance D1 from the position where the virtual line L2 passes to the inner wall in one direction (for example, the −X direction) and the position where the virtual line L2 passes The distance D2 to the inner wall in a direction opposite to the one direction (for example, the + X direction) is different.

  Furthermore, paying attention to the change in the inclination of the inner wall of the mixing vessel 30, as shown in FIG. 7, the direction of the inner wall of the mixing vessel 30 in the −X direction with respect to the liquid As a result, the side wall portion 30sw extending in the vertical direction is responsive to a change in the X coordinate relatively shorter than in the case of going in the + X direction.

  In other words, focusing on the amount of change in the angle between the inner wall of the mixing tank 30 and the horizontal plane (XY plane) (the amount of change in the inner wall angle), when the position of the liquid injection port 30in is used as a reference, the predetermined amount in the + X direction The change amount of the inner wall angle with respect to the movement of the distance is different from the change amount of the inner wall angle with respect to the movement of the predetermined distance in the −X direction.

  In other words, the first change amount and the second change amount defined below are different. Here, the first change amount is a predetermined distance from the liquid inlet 30in in the first direction (for example, the −X direction) from the bottom 30bt to the side wall 30sw on the inner wall surface of the mixing tank 30. This corresponds to the amount by which the angle formed between the inner wall surface and the horizontal plane (here, the XY plane) changes in the traveling path. In addition, the second amount of change is in a second direction opposite to the first direction from the liquid injection port 30in (for example, from the bottom 30bt to the side wall 30sw) on the inner wall surface of the mixing tank 30 (for example, This corresponds to the amount by which the angle formed between the inner wall surface and the horizontal plane (here, the XY plane) changes in a path traveling a predetermined distance in the + X direction.

  In the present embodiment, the liquid inlet 30in is provided at a position deviated in the first direction from the center of the bottom 30bt, and in the second direction based on the liquid inlet 30in of the bottom 30bt of the mixing tank 30. An inclined portion 30tp is provided. Thereby, the first change amount is relatively larger than the second change amount.

<(4) Convection of test liquid generated in mixing tank>
FIG. 8 is a diagram for explaining the convection of the test liquid Ex injected from the liquid injection port 30in into the internal space region 30sp. In FIG. 8, rough flows of the high-concentration test solution and the low-concentration test solution are indicated by thick arrows.

  As described above, the liquid injection port 30in is provided at a position shifted from the center line L1 of the mixing tank 30, and is provided at a position shifted from the center of the bottom 30bt. For this reason, in the internal space region 30sp, the space region on the −X side based on the virtual line L2 is smaller than the space region on the + X side based on the liquid inlet 30in.

  With such a structure, the test liquid Ex (high-concentration test liquid) injected from the −X side portion of the liquid injection port 30in once flows into the −X side space region of the internal space region 30sp. However, since the space area on the −X side is narrow, the high concentration test solution easily flows into the space area on the + X side of the internal space area 30sp. The flow of the high-concentration test solution joins the flow of the test solution Ex (low-concentration test solution) injected from the + X side portion of the liquid inlet 30in into the + X side space region of the internal space region 30sp. Easy to do. For this reason, due to the structure of the mixing tank 30, convection of the test liquid Ex, in which the high-concentration test liquid and the low-concentration test liquid are easily mixed and stirred, occurs. At this time, the flow of the test liquid Ex in the internal space region 30sp tends to be turbulent.

  FIG. 9 temporarily moves the liquid injection port 30in to the center of the bottom 30bt by moving the liquid injection port 30in on the center line L1 of the mixing tank 30 with the mixing tank 30 according to the present embodiment as a reference, and removes the inclined portion 30tp. It is a cross-sectional schematic diagram which shows the structure of the mixing tank 30P which concerns on the comparative example.

  As shown in FIG. 9, in the mixing tank 30P according to the comparative example, the liquid injection port 30inP is provided on the center line L1P of the mixing tank 30P and provided at the center of the bottom 30btP. For this reason, the center line L1P of the mixing tank 30P and the virtual line L2P extending in the + Z direction from the center of the liquid inlet 30inP become the same. Therefore, in the internal space region 30spP of the mixing tank 30P, the distance DP from the imaginary line L2P to the inner wall at an arbitrary position of the mixing tank 30P is substantially constant in each XY cross section.

  FIG. 10 is a diagram for explaining the convection of the test liquid Ex injected from the liquid inlet 30inP into the internal space region 30spP. In FIG. 10, as in FIG. 8, rough flows of the high concentration test solution and the low concentration test solution are indicated by thick arrows.

  In the structure of the mixing vessel 30P according to the comparative example described above, the internal space area 30spP has a space area in the −X direction based on the liquid inlet 30inP, and a space area in the + X direction based on the liquid inlet 30inP. Have approximately the same area.

  For this reason, as shown in FIG. 10, the test solution Ex (high-concentration test solution) injected from the −X side portion of the liquid inlet 30 inP is placed in the −X side space region of the internal space region 30spP. Flow in. On the other hand, the test solution Ex (low-concentration test solution) injected from the + X side portion of the liquid inlet 30inP flows into the + X side space region of the internal space region 30spP. Therefore, compared to the case of the mixing tank 30 according to the present embodiment shown in FIG. 8, convection that promotes mixing and stirring of the high-concentration test solution and the low-concentration test solution is relatively unlikely to occur. .

<(5) Behavior of test liquid in initial stage of injection into mixing tank>
According to the structure of the mixing tank 30 according to the present embodiment, the high-concentration test liquid and the low-concentration test liquid are also determined by the behavior of the test liquid Ex in the stage immediately after the injection of the test liquid Ex into the mixing tank 30 (initial stage of injection). Mixing and stirring with the test solution is promoted.

  FIGS. 11 to 16 are schematic diagrams showing the state of the test solution Ex in the mixing tank 30 at the initial stage of the injection. In FIGS. 11 to 16, the shape of the inner edge of the XZ cross section near the bottom 30 bt of the mixing tank 30 is drawn by a thick line, and the XZ cross section of the liquid surface Exs of the test liquid Ex is drawn by a solid line. Hereinafter, the behavior of the test solution Ex in the mixing tank 30 in the initial stage of the injection will be described with reference to FIGS.

  In the initial stage of the injection, the test liquid Ex exhibits the following behaviors (I) to (VI) sequentially in the mixing tank 30.

(I) As shown in FIG. 11, the foremost part of the test liquid Ex reaches from the fine channel 20 to the liquid inlet 30 in of the mixing tank 30. Until the state shown in FIG. 11, the liquid level Exs of the test liquid Ex is substantially equal to the center line (line parallel to the Z axis) of the flow path from the fine flow path 20 to the liquid inlet 30in. It moves in the + Z direction while maintaining the orthogonal state.

(II) When the liquid surface Exs reaches the boundary between the liquid inlet 30in and the inclined portion 30tp, the liquid surface Exs is inclined at a substantially constant angle with respect to the Z axis as shown in FIGS. And gradually progresses in the internal space area 30sp of the mixing tank 30.

(III) When the liquid surface Exs reaches the boundary between the inclined portion 30tp and the liquid reservoir 30ph, it is caused by the difference between the angle of the inclined portion 30tp with respect to the horizontal plane (XY plane) and the angle of the liquid reservoir 30ph. Therefore, the force that suppresses the progress of the test liquid Ex into the liquid reservoir 30ph by the surface tension is more than the force that the test liquid Ex tries to advance into the liquid reservoir 30ph according to the own weight of the test liquid Ex. It becomes a large state. At this time, as shown in FIG. 14, the shape of the liquid surface Exs forms a convex surface by increasing the amount of the test liquid Ex injected into the internal space region 30sp.

(IV) When the amount of the test liquid Ex injected into the internal space region 30sp increases and the contact angle of the test liquid Ex with the bottom 30bt exceeds a predetermined angle at the boundary between the inclined portion 30tp and the liquid reservoir 30ph, The force with which the test liquid Ex tends to advance into the liquid reservoir 30ph in accordance with the own weight of the test liquid Ex becomes larger than the force with which the advance of the test liquid Ex into the liquid reservoir 30ph is suppressed by surface tension. At this time, as shown in FIG. 15, the balance of the force at the interface where the three phases of the solid phase, the liquid phase, and the gas phase are in contact (three-phase interface) is broken, and the test liquid Ex flows vigorously into the liquid reservoir 30ph. At the same time, the shape of the liquid surface Exs becomes concave. When the liquid surface Exs changes from a convex surface to a concave surface in this manner, a portion of the test liquid Ex in the vicinity of the liquid surface Exs shakes violently. As a result, a turbulent flow occurs near the liquid surface Exs of the test liquid Ex, and the mixing and stirring of the test liquid Ex are promoted.

(V) Further, as shown in FIG. 16, in accordance with the increase in the amount of the test solution Ex injected into the internal space region 30sp, the shape of the liquid surface Exs becomes convex based on the position of the new three-phase interface as a base point. To form

(VI) Thereafter, the same behavior as the behavior (IV) occurs, and the mixing and stirring of the test liquid Ex are promoted. Then, behaviors similar to the behavior (V) and the behavior (IV) are sequentially performed.

  In this manner, the behavior similar to the behavior (V) and the behavior (IV) is alternately repeated as appropriate, so that the liquid surface Exs violently shakes whenever the behavior similar to the behavior (IV) occurs, and the test liquid Ex Mixing and stirring are promoted.

<(6) Injection molding device and molding die>
FIG. 17 is a diagram showing a schematic configuration of an injection molding apparatus and a molding die for molding the mixing tank 30 and the microfluidic chip 1 including the same.
As shown in FIG. 17, the injection molding apparatus 100 mainly includes a hopper 102, a cylinder 104, an injection device 106, a molding die 110, an ejector mechanism 130, and the like.
The hopper 102 is a portion serving as a resin supply source, and is connected to the cylinder 104. The base end of the cylinder 104 is connected to an injection device 106, and the front end of the cylinder 104 is connected to a molding die 110. A screw for kneading the resin is built in the cylinder 104.
The molding die 110 is composed of a fixed die 112 and a movable die 114, and a cavity 116 is formed in a state where these are abutted.
The movable mold 114 has a convex portion 118 for forming the mixing tank 30 of the microfluidic chip 1 and a convex portion 120 for forming the injection / discharge port 40. The convex portions 118 and 120 have cavities. 116.

Particularly, the convex portion 118 is a resin transfer portion for forming the mixing tank 30, and has the same shape as the internal space area 30sp of the mixing tank 30 (see FIG. 5). Therefore, an axis (118L) similar to the axis L1 of the mixing tank 30 exists at the center of the convex portion 118, and the convex portion 118 (particularly, the bottom) has an asymmetric shape with respect to the central axis 118L.
Further, the side surface 118sw of the convex portion 118 is a vertical surface orthogonal to the horizontal plane, and corresponds to the side wall portion 30sw of the mixing tank 30. The side surface 118sw of the projection 118 has a surface roughness of 0.01 to 5 μm. The “surface roughness” here indicates an arithmetic average roughness Ra based on JIS B 0601: 2013. The arithmetic average roughness Ra is basically a value obtained by extracting a reference length from a roughness curve in the direction of the average line, and summing and averaging the absolute values of deviations from the average line of the extracted portion to the measurement curve. is there. According to such a value, the influence of one scratch (irregularity) on the measured value is extremely small, and a stable result is obtained.

The ejector mechanism 130 mainly includes an ejector plate 132, ejector pins 134 and 136 (projection pins), a moving mechanism 138, and the like.
The base ends of the ejector pins 134 and 136 are fixed to the ejector plate 132, and the distal ends of the ejector pins 134 and 136 penetrate the movable mold 114 slidably. The ejector plate 132 is provided with a moving mechanism 138. The moving mechanism 138 is a mechanism that slides the ejector plate 132.

<(7) Manufacturing method of molding die (method of forming convex portion 118 of movable mold 114)>
First, a base material of the movable mold 114 is prepared, and the base material is subjected to cutting processing to form a concave portion corresponding to the cavity 116, and is subjected to machining center processing using a ball end cutter to form the mixing tank 30. Projections 118 (projection precursors) and projections 120 for forming the injection / ejection port 40 are formed. As described above, since the convex portion 118 has an asymmetric shape with respect to the central axis 118L, it is difficult to form the convex portion 118 by turning the base material with the tool fixed and performing lathing. Here, machining is performed on the base material using a ball end cutter. In such a case, the convex precursor is formed to have an asymmetric shape with respect to the central axis 118L.
A known machining center can be used as appropriate.
Thereafter, a known mirror polishing treatment, a YEPCO treatment or a blast treatment is performed on the side surface of the convex portion precursor of the convex portion 118, and the surface roughness of the side surface is set to 0.01 to 5 μm.
Any of these surface treatments may be performed, and practically, it is preferable to perform the JEPC treatment. “Jepco treatment” is a low-pressure microblast treatment that combines a sandblasting technique and a shot peening technique. According to the JEPCO treatment, the surface can be easily and reliably modified simply by spraying a powder (agent) developed for surface modification without using any heating or solvent.
It should be noted that in the known mirror polishing, JEPCO, or blasting, a surface (a bottom surface or the like) other than the side surface of the projection precursor of the projection 118 may be added, or the projection 120 may also be added. May be.

<(8) Manufacturing method of microfluidic chip (including micromixer) using injection molding apparatus and molding die>
First, when manufacturing the mixing tank 30, the molding die 110 is manufactured as described above, and then the resin is molded using the molding die 110.
More specifically, as shown in FIG. 17, in a state where the molding die 110 is installed at a predetermined position of the injection molding apparatus 100, the fixed die 112 and the movable die 114 are abutted to form a cavity 116 (mold clamping step).
Thereafter, the injection device 106 is operated while supplying the resin from the hopper 102 to inject the resin 140 from the cylinder 104 and fill the cavity 116 in the molding die 110 with the resin 140 (injection step). In such a case, the resin 140 passes through the sprue and the gate in order, and is filled in the cavity 116.
When the resin 140 is filled in the cavity 116, the resin 140 is cooled by the molding die 110 itself and tends to shrink. Therefore, the resin 140 is additionally supplied from the cylinder 104 to maintain the pressure, and the resin 140 is shrunk by molding. It prevents dimensional changes of products and poor transfer (pressure keeping process).
Thereafter, the resin 140 is cooled in the molding die 110 until the temperature reaches a temperature at which the resin molded product can be taken out of the molding die 110 (cooling step).

Thereafter, when a predetermined time has elapsed and the resin 140 has sufficiently cooled, the movable mold 114 is separated from the fixed mold 112 as shown in FIG. 18 (mold releasing step). In such a case, the resin molded product 142 is separated from the fixed mold 112 while being attached to the movable mold 114.
Thereafter, the moving mechanism 138 of the ejector mechanism 130 is operated to eject the ejector pins 134 and 136 from the movable mold 114, and the resin molded article 142 is ejected from the movable mold 114 and separated (projecting step).

As a result, in the resin molded product 142, the mixing tank 30 is transferred and formed using the convex portion 118 of the movable mold 114 as a template, and the injection / discharge port 40 is transferred and formed using the convex portion 120 of the movable mold 114 as a template.
Here, in particular, since the surface roughness of the side surface 118sw of the convex portion 118 of the movable mold 114 is 0.01 to 5 μm, the surface roughness of the side wall portion 30sw of the mixing tank 30 to which the transfer has been performed is also 0.01 to 5 μm. It becomes.
Further, here, only the process of transferring the convex portion 118 of the movable mold 114 to the resin 140 is performed, and thereafter, the inner wall surface of the resin molded product 142 is not subjected to the water-repellent coating.
Through the processing in this step, the mixing tank 30 as a micromixer, specifically, a part (part) of the microfluidic chip 1 including the mixing tank 30 is manufactured.

Next, when manufacturing the microfluidic chip 1, a resin substrate including the reaction section 50 is prepared separately from the resin molded product 142, and the resin substrate is bonded to the resin molded product 142 with an adhesive or a seal. The fine channel 20 is formed.
The microfluidic chip 1 is manufactured by the processing in such a step.

According to the above-described embodiment, the convex portion 118 of the movable mold 114 is subjected to mirror polishing, Yepco processing or blasting, and the surface roughness of the side surface 118sw of the convex portion 118 is set to 0.01 to 5 μm. It is transferred to resin 140 and molded. Therefore, the vertical inner wall surface (side wall portion 30sw) of the mixing tank 30 is very smooth and does not need to be water-repellent coated, and there is little trace of unevenness of the ball end cutter due to machining center processing.
Therefore, in the mixing tank 30 having the vertical surface or the microfluidic chip 1 including the same, it is possible to suppress the generation of the liquid residue and the generation of the scratches and dust accompanying the mold release, and the mere transfer of the molding die 110. In one step, the mixing tank 30 or the microfluidic chip 1 capable of realizing these can be provided.

  In addition, in the said embodiment, although the inner wall surface of the mixing tank 30 was mainly comprised by the curved surface, it is not restricted to this, For example, the inner wall surface of a mixing tank may be mainly comprised by the combination of a plane. However, from the viewpoint of suppressing the residual test liquid Ex, for example, it is preferable that the concave portion that forms the bottom of the mixing tank is formed by a curved surface, rather than a combination of flat surfaces.

(1) Preparation of sample (1.1) Sample 1
Using the same injection molding apparatus as in FIG. 17 and following the description of “(8) Manufacturing method of microfluidic chip (including micromixer) using injection molding apparatus and molding die”, FIG. A microfluidic chip 200 (FIG. 19) made of methyl methacrylate having a similar configuration was manufactured.
Here, as a molding die (movable mold) of an injection molding apparatus, a mirror polishing process is performed on a side surface of a convex portion for forming a mixing tank, and a plurality of surfaces having a surface roughness of 0.01 to 0.07 μm. Was used to form a resin molded product 202 having a mixing tank. Thereafter, a substrate 206 made of methyl methacrylate was prepared, and a seal 204 made of methyl methacrylate was interposed between the molded product 202 and the substrate 206 and joined.
In the mixing tank for the molded article 202, the inner diameter φ1 was 10 mm, the height t was 8 mm, and the inner diameter φ2 of the liquid injection port was 2 mm. The fine channel of the microfluidic chip had a width of 1 mm and a height of 1 mm.

(1.2) Sample 2
In the preparation of Sample 1, as a molding die (movable mold) of an injection molding apparatus, a side surface of a convex portion for forming a mixing tank was subjected to a YEPCO treatment, and the surface roughness was 0.1 to 0.3 μm. Were used. Otherwise, Sample 2 was prepared in the same manner as Sample 1.

(1.3) Sample 3
In the preparation of Sample 1, as a molding die (movable mold) of the injection molding apparatus, blast processing was performed on the side surface of the convex portion for forming the mixing tank, and a plurality of surfaces having a surface roughness of 0.5 to 5 μm were formed. Was used. Otherwise, Sample 3 was prepared in the same manner as Sample 1.

(1.4) Sample 4
In the production of Sample 1, as a molding die (movable mold) of the injection molding apparatus, blast processing was performed on the side surface of the convex portion for forming the mixing tank, and a plurality of movable surfaces having a surface roughness of 7 to 10 μm were formed. A mold was used. Otherwise, Sample 4 was prepared in the same manner as Sample 1.

(2) Evaluation of Sample (2.1) Liquid-Sending Test The test liquid was sent to Samples 1 to 4 using the liquid-sending device 300 of FIG.
As shown in FIG. 19, the liquid feeding device 300 mainly includes a pump 302, a nozzle 304, a holder 306, a moving table 308, two ball screw mechanisms 310 and 320, a control device 330, and the like.
The pump 302 and the nozzle 304 are connected via a holder 306. The holder 306 and the moving table 308 are connected via a load cell 340, and the horizontal and height positions of the nozzle 304 are adjusted by the operation of the two ball screw mechanisms 310 and 320. The pump 302, the load cell 340, and the two ball screw mechanisms 310 and 320 (the X-axis motor 312 and the Z-axis motor 322) are connected to a control device 330, and the control device 330 controls the operation of these members.

In the liquid sending test, first, the inlet / outlet of the microfluidic chip 200 as a sample was sealed with a sealing sheet 400 having a three-layer structure. As the sealing sheet 400, the first layer (surface layer) 402 is made of low-density polyethylene having a thickness of 30 to 70 μm, the second layer 404 is made of aluminum having a thickness of 3 to 10 μm, and the third layer (injection / discharge). The layer (the layer directly in contact with the outlet) 406 was formed of an adhesive film having a thickness of 20 to 100 μm.
Thereafter, the controller 330 operates the X-axis motor 312 to adjust the horizontal position of the nozzle 304, and based on the detection result of the load cell 340, operates the Z-axis motor 322 to adjust the height position of the nozzle 304. After adjustment (elevation), the sealing sheet 400 was perforated at the tip of the nozzle 304. Thereafter, the pump 302 was operated to discharge / suction a predetermined amount of the test liquid from the nozzle 304, and the test liquid was injected / discharged (reciprocating liquid supply) to / from the microfluidic chip 200 as a sample. As a test solution, plasma obtained by centrifuging blood collected from a living body was used, and reciprocal sending of the test solution was repeated 10 times.

(2.2) Confirmation of Liquid Remaining For each of Samples 1 to 4, the mixing tank after the test solution sending test was visually observed using SCOPEMAN (registered trademark) MS-804 manufactured by Moritex Corporation. Was checked for remaining liquid. The evaluation magnification was × 25, and the magnification was set such that the inner diameter (φ1; 10 mm) of the mixing tank was within one visual field.
Table 1 shows the evaluation results. In Table 1, the criteria of ○ and × are as follows.
；: No liquid residue is confirmed ×: Liquid residue is confirmed

(2.3) Confirmation of Scratches and Debris On the other hand, for each of Samples 1 to 4, the mixing tank before the test solution sending test was also visually observed using SCOPEMAN (registered trademark) MS-804 manufactured by Moritex Corporation. , Scratches and garbage were checked. The evaluation magnification was × 25, and the magnification was set such that the inner diameter (φ1; 10 mm) of the mixing tank was within one visual field.
Table 1 shows the evaluation results. In Table 1, the criteria of ○ and × are as follows.
○: No scratches and trash are found ×; Scratches and trash are found

(3) Summary As shown in Table 1, when Samples 1 to 3 were compared with Sample 4, the results were good in Samples 1 to 3.
From the above, it is possible to generate a liquid residue by subjecting a convex portion of a molding die for forming a mixing tank to a mirror polishing treatment, a YEPCO treatment or a blast treatment to make the surface roughness 0.01 to 5 μm. It can be seen that this is useful for suppressing the generation of scratches and dust caused by the mold release.

  INDUSTRIAL APPLICABILITY The present invention can be particularly suitably used for manufacturing a micromixer or a microfluidic chip including the same, which can suppress generation of liquid residues and generation of scratches and dust accompanying mold release.

DESCRIPTION OF SYMBOLS 1 Microfluidic chip 20 Micro flow path 30 Mixing tank 30bt Bottom part 30in Liquid inlet 30ph Liquid reservoir 30sp Internal space area 30sw Side wall part 30tp Inclined part 40 Injection / discharge port 50 Reaction part 100 Injection molding device 102 Hopper 104 Cylinder 106 Injection device 110 Molding mold 112 Fixed mold 114 Movable mold 116 Cavity 118 Convex portion 118sw Side surface 120 Convex portion 130 Ejector mechanism 132 Ejector plate 134, 136 Ejector pin 138 Moving mechanism 140 Resin 142 Resin molded product Ex Test liquid Exs Liquid level

Claims (5)

A molding die for molding a micromixer having a vertical surface or a microfluidic chip including the same, comprising a convex portion for forming the micromixer, wherein the convex portion has a surface roughness of 0. In a method for producing a molding die having a size of from 01 to 5 μm,
A step of subjecting the base material to machining center processing using a ball end cutter, and forming a convex precursor for forming a micromixer,
A step of subjecting the surface of the projection precursor to a mirror polishing treatment, a YEPCO treatment or a blast treatment to make the surface roughness of the surface 0.01 to 5 μm,
Equipped with a,
In the step of forming the convex part precursor, the convex part precursor, with respect to its central axis, forming mold manufacturing method, wherein to Rukoto and asymmetrical. A mixing tank having a vertical surface, and a liquid injection port formed at the bottom of the mixing tank, wherein the surface roughness of the side wall of the mixing tank is 0.01 to 5 μm, and the liquid injection port is In a method for manufacturing a micromixer provided at a position shifted from the center of the bottom of the tank,
For the base material, subjected to machining center processing using a ball end cutter, a step of forming a convex precursor for forming the micro-mixer,
A step of subjecting the surface of the projection precursor to a mirror polishing treatment, a YEPCO treatment or a blast treatment to produce a molding die including a projection having a surface roughness of 0.01 to 5 μm,
A step of molding a resin using the molding die,
Equipped with a,
In the step of forming the convex part precursor, the convex part precursor, with respect to its central axis, the manufacturing method of the micro-mixer, wherein to Rukoto and asymmetrical. The method for producing a micromixer according to claim 2 ,
In the step of molding the resin, the micro-mixer is characterized in that only the process of transferring the convex portion of the molding die to the resin is performed, and the inner wall surface of the resin molded product is not subjected to water-repellent coating. Production method. A mixing tank having a vertical surface, and a liquid injection port formed at the bottom of the mixing tank, wherein the surface roughness of the side wall of the mixing tank is 0.01 to 5 μm, and the liquid injection port is A micromixer provided at a position deviated from the center of the bottom of the tank, a fine flow path through which a liquid flows and communicating with the micromixer, and a fine flow path provided on the fine flow path; And a reaction section in which a reaction substance that reacts with a substance contained in the liquid injected into the micromixer or the liquid discharged from the micromixer is fixed. ,
For the base material, subjected to machining center processing using a ball end cutter, a step of forming a convex precursor for forming the micro-mixer,
A step of subjecting the surface of the projection precursor to a mirror polishing treatment, a YEPCO treatment or a blast treatment to produce a molding die including a projection having a surface roughness of 0.01 to 5 μm,
A step of molding a resin using the molding die,
A step of joining a resin substrate including the reaction section to the resin molded product to form the fine flow path,
Equipped with a,
In the step of forming the convex part precursor, the convex part precursor, with respect to its central axis, the manufacturing method of the microfluidic chip, wherein to Rukoto and asymmetrical. The method for manufacturing a microfluidic chip according to claim 4 ,
In the step of molding the resin, a microfluidic chip is characterized in that only a process of transferring a convex portion of the molding die to the resin is performed, and a water-repellent coating is not performed on an inner wall surface of the resin molded product. Manufacturing method.

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