JP2014006049A - Method for manufacturing micro flow channel chip - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for manufacturing a micro flow channel chip, capable of removing the recess of a film without unnecessarily heating a substrate.SOLUTION: A manufacturing method includes the first step of joining a film covering a flow channel to the surface of a substrate having a flow channel groove opened in one surface, and the second step of holding the substrate having the film jointed thereto with face down and heating the film by a heat source disposed below the film. When a part corresponding to the flow channel groove of the film is recessed into the flow channel groove in the first step, in the second step, the recessed part of the film can be returned flat. Thus, the recess of the film is removed without unnecessarily heating the substrate.

Description

  The present invention relates to a method for manufacturing a microchannel chip.

  In recent years, research on miniaturization of chemical reaction systems and analysis systems called microreactors and microanalysis systems has been actively conducted. Advantages of miniaturization of the system include that a test can be performed with a very small amount of specimen and that the amount of discharged waste liquid is reduced. In addition, it is possible to carry a space-saving and inexpensive system.

  Such a system is expected to be applied to analysis and synthesis of nucleic acids, proteins, sugar chains and the like, rapid analysis of trace chemical substances, and high-throughput screening of pharmaceuticals and drugs. Further, since the ratio of the surface area to the volume is improved, heat transfer and mass transfer can be speeded up, so that precise control of reaction and separation, high speed and high efficiency, and suppression of side reactions are expected.

  As a specific system, studies using a microchannel chip having a microchannel have been made. In general, a microchannel chip is manufactured by bonding another substrate or a film to a substrate on which a microchannel is formed by fine processing. Since the substrate and the film are required to have high-precision dimensions, many resin substrates and resin films that are easy to process are used. However, when a resin film is affixed to a resin substrate on which microchannels are formed, the resin film is recessed into the microchannels, resulting in variations in the dimensions of the microchannels.

  In order to solve such a problem, a method disclosed in Patent Document 1 has been proposed. In the method disclosed in Patent Document 1, after the resin substrate and the resin film are joined by thermal fusion, the resin substrate and the resin film are thermally annealed to eliminate the dent.

International Publication No. 2009/110270 Pamphlet

  However, since the method described in Patent Document 1 heats the entire resin substrate and resin film, the resin substrate is unnecessarily heated. Unnecessary heating of the resin substrate may cause distortion or warpage of the resin substrate. Furthermore, since the method described in Patent Document 1 requires a long heating time, the resin substrate can be distorted or warped.

  The present invention has been made in view of the above problems, and provides a method of manufacturing a microchannel chip that can eliminate the dent of the film without unnecessarily heating the substrate.

Such an object is achieved by the present invention described in the following (1) to (6).
(1) A first step of bonding a film covering the flow channel groove to the surface of the substrate having a flow channel groove opened on one surface; and the substrate having the film bonded is directed downward. And a second step of heating the film by a heat source provided below the film, and a portion corresponding to the flow channel groove of the film in the first step is the flow channel groove A method of manufacturing a microchannel chip, characterized in that, when the film is invaded, the indented portion of the film is returned flat in the second step.
(2) The method of manufacturing a microchannel chip according to (1), wherein the heat source is provided apart from the film.
(3) The microchannel chip manufacturing method according to (1) or (2), wherein the heat source has a heating surface larger than the surface of the substrate.
(4) In the second step, the microchannel chip manufacturing method according to (3), in which the surface of the substrate and the heating surface are arranged in parallel and heated.
(5) In the second step, any one of (1) to (4), wherein a spacer that keeps a distance between the surface of the substrate and the heating surface constant is provided between the heating surface and the film. The manufacturing method of the microchannel chip | tip of description.
(6) The macro flow according to any one of (1) to (5), wherein the second step includes at least one of a step of pressurizing the inside of the channel groove and a step of depressurizing the outside of the membrane. Road chip manufacturing method.

  According to the present invention, since the film is heated while being held downward, the dent can be quickly eliminated by the action of gravity or the like. In addition, since the substrate is heated from the side of the film, the substrate is not unnecessarily heated, and the occurrence of distortion and warpage of the substrate can be effectively prevented.

It is a perspective view of the microchannel chip concerning the embodiment of the present invention. It is sectional drawing explaining the manufacturing process of the microchannel chip which concerns on embodiment of this invention. It is sectional drawing explaining the manufacturing process of the microchannel chip which concerns on embodiment of this invention. It is sectional drawing explaining the manufacturing process of the microchannel chip which concerns on embodiment of this invention. It is sectional drawing explaining the manufacturing process of the microchannel chip which concerns on embodiment of this invention. It is sectional drawing explaining the manufacturing process of the microchannel chip which concerns on embodiment of this invention.

  Hereinafter, a preferred embodiment of a method for producing a microchannel chip of the present invention will be described in detail with reference to the drawings.

First, the microchannel chip 1 according to the present embodiment will be described.
FIG. 1 is a perspective view of a microchannel chip 1 according to the present embodiment. The microchannel chip 1 of this embodiment is an instrument for reacting or analyzing a supplied sample in an internal microchannel.

  As shown in FIG. 1, the microchannel chip 1 of this embodiment includes a substrate 2 on which a channel groove 21 is formed and a film 3 bonded to the substrate 2 so as to cover the channel groove 21. In FIG. 1, the flow channel 21 is indicated by a solid line, but is not formed on the surface of the micro flow channel chip 1 but formed on the substrate 2.

In the present embodiment, the substrate 2 has a plate shape, and a flow channel 21 is formed so as to open to one surface 22 thereof.
As the material of the substrate 2, a thermoplastic resin can be used. For example, polyolefin such as polyethylene (PE), polypropylene (PP), polymethylpentene (PMP), polyvinyl such as polystyrene (PS), polycarbonate (PC). Polyacryl such as polymethyl methacrylate (PMMA), cycloolefin polymer (COP), cycloolefin copolymer (COC), and the like can be used. In particular, it is preferable to use COP or COC in terms of moldability, hardness of the molded substrate, and chemical resistance.

  The channel groove 21 is a part for reacting or analyzing the supplied sample. In the present embodiment, one channel groove 21 is formed along the longitudinal direction of the substrate 2. Moreover, the cross-sectional shape of the flow channel 21 is rectangular.

  The cross-sectional shape of the channel groove 21 is not limited to a rectangle, and can be formed in a polygon such as a triangle or a pentagon, a semicircle, or an ellipse according to the purpose of use of the microchannel chip. Further, the number of flow channel grooves is not limited to one, and a plurality of flow channel grooves may be formed. In addition, a liquid reservoir may be provided at the end of the channel groove 21 or in the middle thereof.

  The surface of the channel groove 21 may be subjected to a surface treatment such as a hydrophilization treatment or a surface treatment functional group formation treatment. As such a surface treatment, for example, a treatment for introducing an oxygen-containing functional group is performed. By introducing the oxygen-containing functional group, the hydrophilicity of the resin surface is improved, and smooth sample feeding becomes possible. Examples of the oxygen-containing functional group to be introduced include functional groups having polarity such as carbonyl groups such as aldehyde groups and ketone groups, carboxyl groups, hydroxyl groups, ether groups, peroxide groups, and epoxy groups. As the introduction process, for example, plasma process, corona discharge process, excimer laser process, flame process, or the like can be used.

  The film 3 is bonded to the surface 22 of the substrate 2 and seals the flow channel 21. In the present embodiment, a resin film is used as the film 3. Examples of the material of the film 3 include polyolefins such as polyethylene (PE), polypropylene (PP), and polymethylpentene (PMP), polyvinyls such as polystyrene (PS), polycarbonate (PC), and polymethyl methacrylate (PMMA). Polyacryl, cycloolefin polymer (COP), cycloolefin copolymer (COC), and the like can be used.

  The membrane 3 is provided with an inlet (not shown) for supplying a sample to the channel groove 21 as necessary. The injection port may be formed in advance, but it is preferable to provide a fragile portion in the membrane 3 and form the injection port immediately before use, since contamination can be prevented well.

  Here, a typical dimension example of the microchannel chip 1 of the present embodiment will be described. The substrate 2 has a length of about 10 mm to 30 mm, a width of about 10 mm to 100 mm, and a thickness of about 0.5 mm to 3.0 mm. The film 3 has a vertical and horizontal dimension equivalent to that of the substrate 2 and a thickness of about 0.1 mm to 0.3 mm. The size of the channel groove 21 can be appropriately designed depending on the application. The width of the channel groove 21 may be a micrometer unit or a millimeter unit, and is preferably 1 μm or more and 1000 μm or less from the viewpoint of reducing the amount of sample or reagent used or the amount of waste liquid discharged, and increasing the speed of heat transfer and mass transfer More preferably, it is 100 μm or more and 300 μm or less. The depth of the flow channel 21 is preferably 10 μm or more and 100 μm or less.

  The microchannel chip of the present embodiment can be combined with a film body, a pump, a valve, a sensor, a motor, a mixer, a gear, a clutch, a microlens, an electric circuit, etc. Can be used for applications.

  Next, a method for manufacturing the microchannel chip 1 of the present embodiment will be described with reference to FIGS. 2-6 is sectional drawing explaining the manufacturing process of the microchannel chip 1 which concerns on this embodiment. FIG. 2 is a diagram illustrating the first step. FIG. 3 is a view showing a state in which a dent is generated in the film 3 due to the bonding of the substrate 2 and the film 3. FIG. 4 is a diagram illustrating a state before the film 3 is heated in the second step, and FIG. 5 is a diagram illustrating a state after the heating. FIG. 6 is a view showing the microchannel chip 1 in a state in which the dent of the film 3 is eliminated.

  The manufacturing method of the present embodiment includes a step of bonding the film 3 to the substrate 2 on which the flow channel 21 is formed (first step), holding the substrate 2 with the film 3 facing downward, and further downward A step of heating the film 3 by the provided heat source 4 (second step). Below, each process is demonstrated in detail.

  Prior to the first step, the substrate 2 and the film 3 are prepared. The substrate 2 may be produced by, for example, injection molding. At this time, if a portion corresponding to the channel groove 21 is formed in the mold in advance, these can be integrally formed at the same time, which is suitable for mass production. In the case of post-processing the channel groove 21, a processing method such as machining by a drill, processing by hot embossing, processing by laser, dry etching pattern processing, wet etching pattern processing, or the like may be selected. Moreover, the film | membrane 3 can be produced by extrusion molding, for example.

(First step)
Next, the film 3 is bonded to the surface 22 of the substrate 2 to produce the microchannel chip 1 in which the substrate 2 and the film 3 are integrated.
The joining is performed, for example, by thermocompression using a hot press. That is, as shown in FIG. 2, the substrate 2 and the film 3 are placed on a hot press machine (not shown), and the film 3 is heated with a force F applied thereto. It is preferable to bond the substrate 2 and the film 3 by thermocompression because the manufacturing conditions can be easily controlled so that the flow channel 21 is not affected even when the flow channel 21 is very small.
In addition to the thermocompression bonding, various methods such as a method using an adhesive, ultrasonic fusion, and laser fusion can be used for joining.

  In thermocompression bonding, bonding is performed by applying a temperature near the softening point or glass transition temperature of the resin used for the substrate 2 or the film 3 for a certain period of time using a heat press. The temperature condition at this time varies depending on the resin material to be used, but it is preferable to perform bonding at a temperature of 70 ° C. or higher and 200 ° C. or lower. For example, when a cycloolefin polymer is used as the material of the substrate 2 and the film 3, a temperature of about 80 ° C. to 100 ° C., a pressure of about 1 MPa to 10 MPa, and a time of about 5 minutes to 20 minutes are preferable. If any of temperature, pressure, and time falls below the lower limit, the substrates may not be sufficiently bonded together, and a gap may remain between the substrates. If any of temperature, pressure, and time exceeds the upper limit, the substrate may be melted excessively and a dimensional error may occur in the flow channel 21 and the like.

  As shown in FIG. 3, the substrate 2 and the film 3 bonded in the first step are in a state where the film 3 is recessed in the flow channel 21 and the film 3 is curved. This is considered to occur because the film 3 softened by heating is pressed into the channel groove 21 by being pressurized. If the membrane 3 is recessed in this way, the cross-sectional area of the flow channel groove 21 becomes small, which may hinder accurate analysis and the like. Further, even if the design is made in consideration of the dent amount in advance, the dent amount is difficult to control, and it is difficult to obtain a highly accurate micro-channel chip 1. Therefore, in this embodiment, the dent is eliminated in the second step.

(Second step)
In the second step, the dent is eliminated by heating again the film 3 bonded to the substrate 2 in the first step. As shown in FIG. 4, the substrate 2 to which the film 3 is bonded is held with the film 3 side facing down during heating. Then, the film 3 is heated by a heat source 4 provided below the film 3. That is, the microchannel chip 1 is heated from one surface to remove the dent.

  Heating is performed at a temperature that is higher than the thermocompression bonding temperature of the substrate 2 and the film 3 and that the film 3 is softened. When the film 3 is heated at such a temperature, it is possible to soften the portion of the film 3 that covers the flow channel 21 in a state where the influence on the bonding portion between the substrate 2 and the film 3 is reduced. The softened portion of the film 3 is deformed downward, that is, outside the substrate 2 by the action of gravity. Thereby, the dent of the film | membrane 3 is eliminated, and the part which covers the flow-path groove | channel 21 of the film | membrane 3 becomes flat as shown in FIG.

  The heating conditions are appropriately adjusted depending on the material of the substrate 2 and the film 3, the size of the flow channel 21 and the size of the recess. For example, when polycarbonate (PC) is used as the substrate 2 and the film 3, the depression of the film 3 can be satisfactorily eliminated by setting the heating temperature to about 150 to 200 ° C. and the heating time to about 60 to 180 seconds.

  When heating, a pressurized fluid may be introduced into the flow channel 21 to pressurize the flow channel 21. Alternatively, the outside of the membrane 3 may be depressurized, or both pressurization and depressurization may be performed. Such pressurization or depressurization acts in a direction to eliminate the dent of the membrane 3. Therefore, dents can be eliminated more quickly by applying pressure or reducing pressure.

  Moreover, it is preferable to heat the film 3 so that the entire surface of the film 3 is heated as much as possible. By applying heat uniformly, dents generated at various positions of the microchannel chip 1 can be uniformly removed.

  As an example of performing uniform heating, there is a method in which the heat source 4 is provided separately from the film 3 and the film 3 is indirectly heated through air. By interposing air, the film 3 can be heated more uniformly than when the heat source 4 is brought into direct contact with the film 3. In addition, when air is present, heating unevenness due to fluctuations in the temperature of the heat source 4 can be reduced.

  Another example is a method of heating with a heat source 4 having a heating surface larger than that of the film 3. Since the heating surface is larger than that of the film 3, the film 3 can be heated uniformly. Furthermore, when the heating surface of the heat source 4 and the film 3 are arranged in parallel, more uniform heating can be performed.

  In the present embodiment, a hot plate is used as the heat source 4. As shown in FIGS. 4 and 5, the spacer 5 is placed on the hot plate, and the microchannel chip 1 is placed on the spacer 5 with the film 3 facing downward. The spacer 5 is formed of a material having low thermal conductivity such as a rubber plate, and keeps the hot plate (heat source 4) and the film 3 in parallel. If it does in this way, the film | membrane 3 will be arrange | positioned in the state spaced apart from the hotplate, and parallel to a hotplate. Therefore, the entire film 3 can be heated uniformly.

  After the second step, the microchannel chip 1 is cooled to cure the film 3 to obtain the microchannel chip 1 shown in FIG. The cooling may be allowed to cool at room temperature, for example. Cooling may be performed with either surface of the microchannel chip 1 as the upper side.

  As described above, the recess of the film 3 generated when the substrate 2 and the film 3 are joined can be eliminated by heating again, and the microchannel chip 1 having the channel grooves 21 with high dimensional accuracy can be obtained.

DESCRIPTION OF SYMBOLS 1 Microchannel chip 2 Substrate 21 Channel groove 22 Surface 3 Film 4 Heat source 5 Spacer

Claims (6)

A first step of bonding a film covering the flow channel to the surface of the substrate having a flow channel opened to one surface;
Holding the substrate to which the film is bonded with the film facing downward, and heating the film with a heat source provided below the film; and
In the first step, when a portion corresponding to the flow channel groove of the film is indented into the flow channel groove, the indented portion of the film is returned flat in the second step. A method of manufacturing a microchannel chip.   The method of manufacturing a microchannel chip according to claim 1, wherein the heat source is provided apart from the film.   The method of manufacturing a microchannel chip according to claim 1, wherein the heat source has a heating surface larger than the surface of the substrate.   4. The method of manufacturing a microchannel chip according to claim 3, wherein in the second step, the surface of the substrate and the heating surface are arranged in parallel and heated.   5. The micro according to claim 1, wherein in the second step, a spacer is provided between the heating surface and the film to maintain a constant distance between the surface of the substrate and the heating surface. A manufacturing method of a channel chip.   6. The method of manufacturing a macro flow channel chip according to claim 1, wherein the second step includes at least one of a step of pressurizing the inside of the flow channel groove and a step of depressurizing the outside of the film. .

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