JP2009047438A - Micro flow-path chip - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a micro flow-path chip having micro channels produced without using a prototype such as a casting mold. <P>SOLUTION: In the micro flow-path chip consisting of at least a first substrate and a second substrate in which the first substrate and the second substrate are bonded, one or more of material layers removable with a medium is formed on the bonded face side of at least one of the substrates and at least one edge part of the material layer removable with the medium is connected to a port opening to the atmosphere. When the material layer is removed by the medium, a micro gap is generated at the site where the material layer was present. By expanding this micro gap, the space capable of functioning as micro channels can be realized. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a microchannel chip and a manufacturing method thereof. More specifically, the present invention relates to a microchannel chip capable of forming a microchannel to be a channel of a medium such as liquid or gas without using a prototype such as a mold, and a method for manufacturing the microchannel chip.

  Recently, microchannels and ports that form channels of a predetermined shape in a substrate, as is known by names such as Micro Total Analysis Systems (μTAS) or Lab-on-Chip (Lab-on-Chip) It has been proposed to perform various operations such as chemical reaction, synthesis, purification, extraction, generation and / or analysis of substances within the microstructure, and some of them have been put into practical use. A structure manufactured for such a purpose and having a fine structure such as a microchannel and a port in a substrate is generally called a “microchannel chip” or a “microfluidic device”.

  Microchannel chips can be used in a wide range of applications such as genetic analysis, clinical diagnosis, drug screening, and environmental monitoring. Compared to the same type of equipment of the common size, the microchannel chip is (1) significantly less sample and reagent usage, (2) shorter analysis time, (3) higher sensitivity, (4) portable to the field. , It can be analyzed on the spot, and (5) can be disposable.

  For example, as shown in FIGS. 8A and 8B, the conventional microchannel chip 100 has at least one hollow microchannel 104 formed on an upper substrate 102 made of a material such as synthetic resin. At least one end of the hollow microchannel 104 is formed with ports 105 and 106 to be input / output ports, and a lower surface made of a transparent or opaque material (for example, glass or synthetic resin film) on the lower surface side of the substrate 102. The substrate 108 is bonded. The presence of the lower substrate 108 seals the ports 105 and 106 and the bottom of the microchannel 104.

  The material, structure and manufacturing method of the microchannel chip as shown in FIGS. 8A and 8B are proposed in, for example, Patent Document 1 and Patent Document 2. Among them, a series of microchannel chips characterized by using polydimethylsiloxane (PDMS) which is an elastomer type silicon resin has been developed. PDMS has excellent mold transferability, transparency, chemical resistance, biocompatibility, etc. for a master (mold) having a fine structure such as a channel, and has particularly excellent characteristics as a constituent member of a microchannel chip. ing.

  FIG. 9 is a process diagram showing an example of a manufacturing method of the microchannel chip 100 as shown in FIGS. 8A and 8B. This manufacturing method is a manufacturing method applying a so-called lithography method, which is frequently used for manufacturing semiconductors. First, in step (a), a silicon wafer 200 having the same size as that of the final product micro-channel chip 100 (for example, 20 mm × 20 mm or 20 mm × 30 mm) is prepared. The silicon wafer 200 can be dried in advance or subjected to a desired pretreatment such as a surface treatment. Thereafter, in step (b), a suitable resist material (for example, negative photoresist SU-8) is spin-coated at a rotational speed of 2000 rpm to 5000 rpm for several seconds to several tens of seconds, dried in an oven, and A resist film 220 having a thickness is formed. Next, in step (c), the resist film 220 is exposed through a mask 240 with an appropriate exposure apparatus (not shown). The mask 240 has a layout pattern corresponding to the channel 104 in the microchannel chip 100. Thereafter, in step (d), development is performed in a suitable developing solution (for example, 1-methoxy-2-propylacetic acid) to produce a master (template) 280 having a microstructure 260 corresponding to the channel 104 on the upper surface. If desired, the master 280 can be washed with an organic solvent (eg, isopropyl alcohol) and distilled water. Furthermore, the surface of the master 280 can be treated with a reactive ion etching system in the presence of trifluoromethane. This reactive ion etching process in the presence of trifluoromethane improves the releasability of the PDMS from the master 280 in a later step. Next, in step (e), the PDMS prepolymer and the curing agent are mixed at an appropriate ratio on the upper surface of the master 280, and the degassed PDMS prepolymer mixed solution is poured. At this time, it is preferable that a mold is used to form a casting mold and a PDMS prepolymer mixed solution is poured into the casting mold. As the PDMS prepolymer mixed solution, for example, SYLGARD 184 SILICONE ELASTOMER manufactured by Dow Corning, USA can be suitably used. This is a mixture of a liquid PDMS prepolymer and a curing agent in a ratio of 10: 1. After coating, the substrate is allowed to stand at room temperature for a sufficient time, or, for example, heated in an oven at 65 ° C. for 1 hour, or heated at 135 ° C. for 15 minutes to be cured to generate the PDMS intermediate substrate 300. The PDMS intermediate substrate 300 is a highly transparent rubber-like resin to which the fine structure 260 of the master 280 is transferred. Thereafter, in step (f), the PDMS intermediate substrate 300 is peeled off from the master 280, and the port 105 (106) communicating with the hollow microchannel 104 below from the upper surface of the PDMS intermediate substrate 300 is formed with the punch 320. A PDMS substrate 102 is obtained. Next, in step (g), the PDMS substrate 102 is bonded to the facing substrate 108 with the channel 104 formation surface facing down. Finally, in step (h), the completed microchannel chip 100 is recovered.

  However, when the lithography method as shown in FIG. 9 is performed, an exposure mask must first be manufactured in order to manufacture a master (mold) 280 to be a prototype. An expensive manufacturing apparatus must be used for manufacturing the mask. Furthermore, an expensive exposure apparatus must be used to expose the resist through the mask. Further, not only a developing device is required after the exposure, but also a disposal treatment of the used developer is required. Therefore, the production of the master (mold) 280 requires a great deal of labor, labor, and cost, which increases the cost of the final microchannel chip 100. Moreover, since the resist mold is hard, durability and adhesion are poor, and the resist mold may be relatively easily damaged. Therefore, each time, the resist master (mold) 280 had to be remade by the procedure as described above. For this reason, the result that the manufacturing cost of the microchannel chip | tip 100 increased further was caused, and it was difficult to supply a disposable chip | tip cheaply.

  Patent Document 3 is composed of a container at least partially formed of an elastic body, and a plurality of chambers are formed in the container so as to be connected or connectable with a flow path. A chemical reaction cartridge for performing a chemical reaction by moving an object in the flow path or the chamber or both by applying an external force to the elastic body, wherein at least one of the flow path and the chamber is: A chemical reaction cartridge is described in which the volume is zero before the fluid substance is introduced. The flow path and the chamber whose volume is zero before the fluid-like substance is introduced are formed by forming a non-adhesive portion in the corresponding flow path and the chamber before bonding the elastic body. This non-bonded portion is formed, for example, by masking the corresponding region during plasma processing or by applying a substance that is not activated by plasma.

However, in the invention of Patent Document 3, the portion masked at the time of plasma processing loses non-adhesive properties over time, and the upper and lower substrates are bonded to each other and the flow path is blocked. Moreover, even if a substance that is not activated by plasma is applied, most substances are activated by plasma and undergo decomposition. Furthermore, the risk that the applied substance will adversely affect the results during the actual analysis cannot be denied. Therefore, in the invention of Patent Document 3, it is impossible to reliably form a zero-volume channel and chamber over time, and the reliability of the analysis result is also impaired.
JP 2001-157855 A US Pat. No. 5,965,237 JP 2005-313065 A

  Therefore, an object of the present invention is to provide a microchannel chip having a microchannel manufactured without using a prototype such as a mold.

  Another object of the present invention is to provide a method of manufacturing a microchannel chip without using a prototype such as a mold in a microchannel chip having a microchannel to be a channel of a medium such as liquid or gas. That is.

  As a means for solving the above-mentioned problem, the invention according to claim 1 is a micro-channel comprising at least a first substrate and a second substrate, wherein the first substrate and the second substrate are bonded to each other. In the chip, at least one material layer removable by the medium is formed on the bonding surface side of at least one substrate, and at least one end of the material layer removable by the medium is open to the atmosphere. A microchannel chip connected to a port to be

  According to the present invention, before using the microchip, the medium is fed through the port, and the material layer is removed, so that a minute gap in a non-adhered state is present at the position where the material layer was present. Is generated. Next, by applying a positive pressure from the port, the non-adhered minute gap can be bulged to generate a void that can function as a microchannel. As a result, it is possible to feed liquid and / or gas from one port into the gap created by the bulge. If both ends of the non-adhered minute gap portion are connected to a port that opens toward the atmosphere, liquid and / or gas can be transferred from one port to the other port. In addition, depending on the form of use, the non-adhered minute gap portion can also function as an on-off valve or a microvalve.

  As a means for solving the above-mentioned problem, the invention according to claim 2 is characterized in that the material layer removable by the medium is at least one kind selected from the group consisting of a circle, an ellipse, a rectangle and a polygon in the middle thereof. The microchannel chip according to claim 1, further comprising one or more enlarged region layers each having a planar shape.

  According to the present invention, after the material layer is removed, the enlarged region portion can function as a liquid reservoir at the time of swelling, and operations such as PCR amplification can be efficiently performed using the liquid reservoir portion. .

  As a means for solving the above-mentioned problems, the invention according to claim 3 is the microchannel chip according to claim 1, characterized in that the material layer removable by the medium is formed to intersect.

  According to the present invention, for example, by forming two material layers that can be removed by a medium so as to intersect, a microchannel chip that can be used for electrophoresis can be easily obtained after the material layer is removed by the medium. .

  As a means for solving the above problem, in the invention according to claim 4, the material layer removable by the medium is formed on the bonding surface side of the second substrate, and the port is formed on the first substrate side. The microchannel chip according to claim 1, 2, or 3.

  According to the present invention, the material layer that can be removed by the port and the medium can be formed separately.

  As a means for solving the above-mentioned problem, in the invention according to claim 5, the material layer removable by the medium is formed on the bonding surface side of the first substrate, and the port is formed on the first substrate side. The microchannel chip according to claim 1, 2, or 3.

  According to the present invention, the material layer that can be removed by the port and the medium can be formed only on one substrate side, so that the other substrate side only needs to be bonded.

  As a means for solving the above-mentioned problems, the invention according to claim 6 is characterized in that the material layer removable by the medium is formed on both the bonding surface side of the first substrate and the bonding surface side of the second substrate, and the port is formed. 4. The microchannel chip according to claim 1, wherein the microchannel chip is formed on a first substrate side.

  According to the present invention, since the minute gap generated after the material layer is removed with the medium is generated between the two substrates, the minute gap itself can be used as a microchannel, and the second substrate and the first substrate are not bonded. The property is further ensured, and when a positive pressure is applied, the minute gap portion is more likely to bulge.

  As a means for solving the above-mentioned problems, the invention according to claim 7 is characterized in that a substance spot layer is further formed at a position corresponding to the material layer removable by the medium. It is a channel chip.

  According to the present invention, materials that are easily decomposed or infiltrated by moisture, oxygen, microorganisms, etc. in the air or materials that are easily moved by impact or environmental pressure are stably sealed or shielded until just before use. And can be stored or protected safely.

  As a means for solving the above-mentioned problems, in the invention according to claim 8, the substance spot layer is located at a position corresponding to a material layer removable by the medium, and on the substrate side where these material layers are not disposed. The microchannel chip according to claim 7, which is formed.

  According to the present invention, the substance spot layer can be formed separately from the material layer that can be removed by the medium.

  As a means for solving the above-mentioned problems, the invention according to claim 9 is characterized in that the substance spot layer comprises chemical reaction reagents, solutes, salts, saccharides, antigens, antibodies, physiologically active substances, endocrine disrupting substances, sugars. Chains, glycoproteins, peptides, proteins, amino acids, DNAs, RNAs, microorganisms, yeasts, fungi, spores, plant fragment tissues, animal fragment tissues, drugs, glass particles, resin particles, magnetic materials 9. The microchannel chip according to claim 7, wherein the microchannel chip is formed of at least one substance selected from the group consisting of particles, metal particles, polymers, swelling gels, and solidified gels.

  According to this invention, both the non-solid substance and the solid substance can be used as the material spot layer forming material.

  As a means for solving the above-mentioned problems, the invention according to claim 10 is characterized in that the first substrate is made of polydimethylsiloxane (PDMS) and the second substrate is made of polydimethylsiloxane (PDMS) or glass. The microchannel chip according to claim 1.

  According to the present invention, the first substrate and the second substrate can be permanently bonded to each other without using an adhesive.

  As a means for solving the above-mentioned problems, the invention according to claim 11 is the method of manufacturing a microchannel chip according to any one of claims 1 to 10, and is desired on the bonding surface side of at least one substrate. According to the pattern, a microchannel chip manufacturing method comprising coating or depositing a material removable by a medium.

  According to the present invention, the material layer that can be removed by the medium according to the mask pattern can be easily formed on the bonding surface side of at least one of the substrates. Compared with the method using a conventional mold, the manufacturing cost is low and the mass productivity is also excellent.

  As a means for solving the above-mentioned problems, the invention according to claim 12 is such that the material layer removable by the medium has a particle size selected from the group consisting of water-soluble, water-insoluble, organic solvent-soluble and organic solvent-insoluble. 12. The method of manufacturing a microchannel chip according to claim 11, wherein the microchannel chip is formed from a material mainly containing powder of 10 μm or less.

  According to the present invention, before using the microchannel chip, by using a material mainly composed of water-soluble, water-insoluble, organic solvent-soluble or organic solvent-insoluble powder having a particle size of 10 μm or less, The material layer can be quickly removed without causing clogging or the like.

  As a means for solving the above-mentioned problem, the invention according to claim 13 is characterized in that the coating or deposition of the material removable by the medium is performed by any means selected from the group consisting of application, spraying and printing of the material. It is a manufacturing method of the microchannel chip | tip of Claim 11 consisting of being performed.

  According to the present invention, since the coating or deposition of the material removable by the medium can be carried out by inexpensive conventional means such as application, spraying or printing, the microchannel chip is compared with the method using the conventional mold. Not only is the production cost even lower, but it is also excellent in terms of mass productivity.

As a means for solving the above-mentioned problem, the invention according to claim 14 is a micro-channel comprising at least a first substrate and a second substrate, wherein the first substrate and the second substrate are bonded to each other. In the chip, at least one material layer removable by the medium is formed on the bonding surface side of at least one substrate, and at least one end of the material layer removable by the medium is open to the atmosphere. A method of using a microchannel chip connected to a port,
The material layer is removed by feeding a medium from one port, a non-adhesive minute gap is generated at a location where the material layer was present, and a positive pressure is applied from the port. This is a method of using a micro-channel chip that is used as a microchannel with or without bulging the gap.

  According to the present invention, there is no microchannel for flowing a sample until it is used as a microchannel chip, but if the material layer is removed with a medium, a non-adhesive minute gap that can function as a microchannel is formed. It can be formed easily. Therefore, compared with a rectangular concave microchannel formed with a conventional mold, the microchannel is less likely to be contaminated by foreign matter in the atmosphere, and a good analysis result can be obtained.

  As a means for solving the above-mentioned problems, the invention according to claim 15 is a method of using a microchannel chip, wherein the medium for removing the material layer is liquid or gas.

  According to the present invention, the material layer can be removed by using either a liquid or a gas medium, which is easy to use.

  According to the present invention, in a microchannel chip produced by forming a material layer removable by a medium on one substrate surface and bonding both substrates together, if the material layer is removed by a medium immediately before use, Since a non-adhesive minute gap is formed at the location where the material layer existed, it can be used in the same way as a microchannel manufactured using a conventional mold by pressurizing and expanding the minute gap. Can do. As a result, the microchannel chip can be mass-produced extremely easily compared to the case where the microchannel chip is manufactured by the conventional lithography method, and the microchannel chip is provided at a very low cost. be able to. In addition, since the minute gap has a height corresponding to the thickness of the material layer removed by the medium, it is more time-consuming than when the non-adhesive state is expressed by surface modification treatment as in the known document 3. It is hard to cause a situation that changes to an adhesive state.

  Compared to a microchannel chip having a conventional microchannel, another effect of the microchannel chip having a material layer removable by the medium of the present invention is that bubbles are mixed in the conventional microchannel during liquid feeding. Whereas it was easy, in the case of the microchannel chip of the present invention, a void functioning as a microchannel does not occur unless the non-adhesive minute gap generated by removing the material layer with a medium is expanded. There is almost no air bubbles mixed in during liquid feeding. When bubbles were mixed in the microchannel, not only the subsequent liquid feeding became difficult, but also the removal of bubbles was very difficult. Therefore, in a microchannel chip having a conventional microchannel, it is necessary to pay close attention so that bubbles are not mixed during liquid feeding, and wasted time is spent on the liquid feeding work. It was. According to the microchannel chip of the present invention, it is not necessary to spend useless labor on the liquid feeding operation.

  1A is a schematic plan view of an example of a microchannel chip according to the present invention, and FIG. 1B is a cross-sectional view taken along line 1B-1B in FIG. 1A. The microchannel chip according to the present invention includes a first substrate 3 and a second substrate 5 as in the conventional microchannel chip, and the first substrate 3 inputs and outputs a medium such as liquid or gas. Ports 7 and 9 to be mouths are arranged. The first substrate 3 and the second substrate 5 are bonded to each other at portions other than the material layer 11 and the ports 7 and 9 that can be removed by the medium. As will be described in detail below, the material layer 11 that can be removed by the medium is a portion to be a microchannel in a conventional microchannel chip after being removed. However, since the port 7 and the port 9 are normally blocked by a material layer 11 that can be removed by a medium, a sample such as a liquid or a gas cannot be sent from one port to the other as it is. When the material layer 11 is removed with a medium such as a liquid or a gas before use, a non-adhesive minute gap is formed between the substrates, and the minute gap is bulged or left without being bulged. The same action and function as the other channels can be exhibited. If the material layer removing medium can be discharged out of the chip together with the material layer at some point, the port 9 does not necessarily exist.

  FIG. 2 is a partial schematic cross-sectional view showing an example of a usage pattern of the microchannel chip 1 of the present invention. In the microchannel chip 1 of the present invention, as shown in FIG. 2 (A), an adapter 14 is disposed at the opening of the port 7 to be a liquid or gas introduction section, and the adapter 14 is provided with a feeding tube. 16 is connected. Needless to say, the shape of the adapter 14 is not limited to that illustrated. Instead of being partially inserted into the port, it may be directly fixed to the first substrate 3. Alternatively, a configuration in which the inlet tube 16 is directly connected to each port without using the adapter 14 is also possible. A medium (liquid or gas) is fed from the feeding tube 16 at a pressure of several kPa to several tens of kPa. As a result, as shown in FIG. 2B, only the first substrate portion corresponding to the material layer 11 that can be removed by the medium slightly bulges, and the feeding medium and the material layer 11 come into contact with each other. When the medium is water 19 and the material layer 11 is formed of a water-soluble material, the material layer 11 dissolves in the water 19 and is discharged from a port (not shown) at the other end. Thereafter, when the inside of the channel is dried by continuously feeding the medium in place of air or the like, a material layer is formed between the first substrate 3 and the second substrate 5 as shown in FIG. A minute gap 32 having a height corresponding to the thickness of 11 is formed. This minute gap 32 becomes a non-adhesive portion. Thereafter, when a gas (for example, air) is fed from the feeding tube 16 at a high pressure (for example, 1 kPa to 100 kPa) or a target liquid is injected into the port 7 while applying a positive pressure, FIG. As shown in FIG. D), only the portion of the first substrate 3 corresponding to the minute gap 32 slightly bulges, resulting in a void 18 that can function as a microchannel, which allows liquid and / or gas in the port 7 to flow. Can be transported to port 9.

  As the material layer 11 that can be removed by the medium, a water-soluble material or an organic solvent-soluble material can be used, but a water-insoluble material or an organic solvent-insoluble material can also be used equally. Examples of the water-soluble material include starch, agar, gelatin, glue, polyethylene glycol, and methyl methacrylate. Examples of the organic solvent-soluble material include styrene and methyl methacrylate. The organic solvent is preferably an alcohol solvent. Examples of the water-insoluble material include talc, metal nanocolloid, calcium carbonate, and titanium oxide. Organic solvent insoluble materials are, for example, participating aluminum, barium sulfate and the like. The medium is not limited to solvents such as liquids. A gas (for example, air, carbon dioxide gas, nitrogen gas, etc.) can also be used as the medium. For example, the water-soluble, water-insoluble, organic solvent-soluble or organic solvent-insoluble material can be removed by blowing off with a gas.

  The material removable by the medium is preferably a material mainly composed of powder having a particle size of 10 μm or less. If the particle size of the powder is more than 10 μm, the coating or deposition operation when forming the material layer may not proceed smoothly, the dissolution rate may be slow, or in the case of an insoluble material, clogging may occur in the channel There is sex.

  The pattern of the material layer 11 that can be removed by the medium is not limited to the illustrated linear shape. In consideration of the purpose and / or use, etc., the material layer 11 having various patterns such as a Y-shape, an L-shape, an S-shape, an X-shape, and a cross shape may be adopted in consideration of the purpose and / or the use. it can. Further, the material layer 11 that can be removed by the medium may have an enlarged shape portion having an arbitrary planar shape such as a circle, an ellipse, a rectangle, and a polygon in addition to the linear portion. As will be described in detail below, the enlarged shape portion can function as a reaction chamber or a liquid reservoir during swelling, and the PCR chamber or the like can be efficiently performed using this reaction chamber or the liquid reservoir portion. Can do. A plurality of material layers 11 that can be removed by the medium can be formed instead of only one. The plurality of material layers 11 that can be removed by the medium can be arranged in any form such as parallel arrangement or cross arrangement. The cross arrangement is useful as a conventional cross-injection electrophoresis chip.

  The width of the material layer 11 removable by the medium can be substantially the same as, or larger or smaller than, the width of the microchannel in the conventional microchannel chip. Generally, the width of the material layer 11 that can be removed by the medium is about 10 μm to 3000 μm. This width can be appropriately selected according to the application. For example, when used as a channel itself, it is about 10 μm to several hundred μm, and when used as a reaction chamber or a liquid storage chamber, it can have a width or inner diameter of about several hundred μm to 3000 μm.

  Although the film thickness of the material layer 11 removable with a medium changes according to the material layer forming method to be used, it is preferable that it is generally in the range of 10 nm to 300 μm. When the film thickness of the material layer 11 that can be removed by the medium is less than 10 nm, the material layer 11 that can be removed by the medium is not uniformly formed, and an adhesion site and a non-adhesion site are generated in island shapes and function as a microchannel. It becomes difficult to make. On the other hand, when the film thickness of the material layer 11 that can be removed by the medium is more than 300 μm, the removal may take a long time or may cause clogging. In the case of the coating method, the thickness of the material layer 11 that can be removed by the medium is in the range of 50 nm to 300 μm, preferably in the range of 80 μm to 200 μm, and more preferably in the range of 100 nm to 100 μm. In the case of the printing method, the film thickness of the material layer 11 that can be removed by the medium is in the range of 500 nm to 100 μm, preferably in the range of 800 nm to 80 μm, and more preferably in the range of 1 μm to 50 μm.

  FIG. 3 is a process explanatory diagram of an example of a method for manufacturing the microchannel chip 1 of the present invention. First, in step (a), a mask 20 on which a pattern of a predetermined channel design is formed is prepared. The mask can be formed of a synthetic resin film (for example, a PET film, a vinyl chloride film, etc.) having a thickness of about 0.01 mm to 1 mm or a metal foil. Therefore, a mask having a desired penetration pattern can be manufactured by punching a film or metal foil with a die, cutting with a blade, or machining with a laser or the like by electric discharge machining or milling. In step (b), the mask 20 is bonded to the upper surface of a base material (for example, PDMS) to be the second substrate 5 by utilizing a phenomenon such as adsorption, or bonded by adhesion. In step (c), a material removable by the medium is sprayed from the upper surface of the mask 20, or is coated or deposited by a known and conventional method such as brushing or roll coating. In step (d), when the mask 20 is peeled off, the material layer 11 that can be removed with a medium having a pattern corresponding to the channel design remains on the upper surface of the second substrate 5. The material layer 11 that can be removed by the medium may be dried or may be left undried. In step (e), the upper surface on which the material layer 11 removable by the medium of the second substrate 5 exists and the lower surface side of the first substrate 3 in which the through holes for the ports 7 and 9 are opened are surface-modified. Process. By performing the surface modification treatment, the adhesive strength between the substrates can be increased. As the surface modification treatment method, an oxygen plasma treatment method, an excimer UV light irradiation treatment method, or the like can be used. The oxygen plasma treatment method can be performed by a plasma discharge treatment apparatus in the presence of oxygen. Since the excimer UV light irradiation treatment method can be carried out in an air atmosphere at atmospheric pressure by a dielectric barrier discharge lamp, the treatment cost is low. Next, in step (f), the surfaces subjected to the surface modification treatment are bonded together, and the first substrate 3 and the second substrate 5 are permanently bonded. When the delivery tube is directly connected to each port, the microchannel chip 1 of the present invention is completed at this stage. However, if desired, finally, in step (g), the adapter 14 for connecting the delivery tube can be fixed to each part of the ports 7 and 9 to obtain the microchannel chip 1 of the present invention.

  4A and 4B are process explanatory views of an example of a manufacturing method of the microchannel chip 1A according to another embodiment. The manufacturing method shown in FIGS. 4A and 4B is basically the same as the manufacturing method shown in FIG. First, in step (a), a mask 20A having a predetermined channel design is prepared. Unlike the mask 20 of FIG. 3, this mask has a through-hole 22 for forming a liquid reservoir portion. In step (b), the mask 20A is bonded to the upper surface of a base material (for example, PDMS) to be the second substrate 5 by utilizing a phenomenon such as adsorption or bonded by adhesion. In step (c), a material removable by the medium is sprayed from the upper surface of the mask 20A or coated or deposited by a known and conventional method such as brushing. In step (d), when the mask 20A is peeled off, the material layer 11A having a pattern corresponding to the channel design and removable by the medium remains on the upper surface of the second substrate 5. The material layer 11A that can be removed with this medium has an enlarged region 24 that should be a liquid reservoir portion, unlike the material layer 11 that can be removed with the medium of FIG. In step (e), the upper surface on which the material layer 11A that can be removed by the medium of the second substrate 5 and the lower surface side of the first substrate 3 in which the through holes for the ports 7 and 9 are opened are modified. Process. Next, in step (f), the surfaces subjected to the surface modification treatment are bonded together, and the first substrate 3 and the second substrate 5 are permanently bonded. In step (g), two port portions having a predetermined thickness (for example, 1 mm) that can also be used as a port and a through hole 26 having the same shape as the shape of the liquid reservoir portion 24 (for example, a circle having a diameter of 5 mm) are formed. The lower surface side of the silicone rubber sheet 28 and the upper surface side of the laminate obtained in the step (f) are subjected to surface modification treatment. The diameter of the through hole 26 is preferably the same as or larger than the diameter of the liquid reservoir portion 24. Finally, in step (h), the through holes 7A and 9A of the silicone rubber sheet 28 and the ports 7 and 9 of the first substrate 3 are aligned and bonded together by permanent adhesion, and the target microchannel chip 1A is attached. Finalize. Although not shown, if desired, the adapter 14 for connecting the delivery tube can be fixed to the through holes 7A and 9A of the silicone rubber sheet 28. The surface modification treatment of the silicone rubber sheet 28 is not an essential requirement of the present invention. The silicone rubber sheet 28 may be simply self-adsorbed to the first substrate 3 without being subjected to surface modification treatment.

  In each of the above manufacturing methods, the material layers 11 and 11A that can be removed by the medium can be disposed not on the second substrate side but on the first substrate side. In this case, since the fine components such as the material layer removable by the port and the medium are all disposed on the first substrate side, the second substrate does not require any fine processing, and the microchannel chip is manufactured. Is further simplified.

  As another embodiment, the material layers 11 and 11A that can be removed by the medium can be disposed on both the second substrate side and the first substrate side. In this case, the height of the gap formed after the material layers 11 and 11A are removed with the medium is doubled, and the non-adhesiveness between the second substrate and the first substrate is further ensured. As a result, there is an advantage that when the positive pressure is applied, the minute gap 32 portion is more easily bulged. Alternatively, the minute gap 32 itself can be used as a microchannel without being pressurized and bulged.

  The material layer 11 that can be removed by the medium can be formed by a method other than the above. For example, the material layer 11 that can be removed by the medium can be formed on the upper surface of the second substrate 5 by printing. For printing, various known and commonly used printing methods such as roll printing, silk printing, pattern printing, transfer, electrostatic copying, etc. can be employed. When the material layer 11 that can be removed by the medium is formed by a printing method, the material layer 11 that can be removed by the medium may be formed of metal fine particles having a particle size of 10 μm or less (for example, Al, As, Au, B, Bi). , Ca, Cd, Cr, Co, Cu, Fe, Ga, Ge, Hg, In, Li, Mg, Mn, Mo, Na, Ni, Pb, Pt, Rh, Sb, Se, Si, Sn, Ti, V Single metal fine particles such as W, Y, Zn or Zr, or two or more kinds of these alloy fine particles, or oxide fine particles (for example, ITO fine particles) of these single metals or alloys, and these organometallic compound fine particles Conductive ink, insulating ink, carbon fine particles, silane agent, parylene, paint, pigment, dye, water-based dye ink, water-based pigment ink, oil-based dye ink, oil-based pigment ink, solvent-based ink, solid ink, etc. Ink, gel ink, such as polymer ink can be suitably used. In order to select a suitable material from these, it is selected based on whether or not it can be removed by a medium such as a gas or a liquid.

  The first substrate 3 in the microchannel chip 1 according to the present invention does not necessarily have elasticity and / or flexibility, but is generally preferably a polymer or an elastomer. When the first substrate 3 is not formed of a material having elasticity and / or flexibility, the portion of the material layer 11 that can be removed by the medium is deformed to become a microchannel in a conventional microchannel chip. It becomes impossible or difficult. Therefore, as a material for forming the first substrate 3, for example, silicone rubber such as polydimethylsiloxane (PDMS), nitrile rubber, hydrogenated nitrile rubber, fluorine rubber, ethylene propylene rubber, chloroprene rubber, acrylic rubber, Preferred are butyl rubber, urethane rubber, chlorosulfonated polyethylene rubber, epichlorohydrin rubber, natural rubber, isoprene rubber, styrene butadiene rubber, butadiene rubber, polysulfide rubber, norbornene rubber, thermoplastic elastomer and the like. Silicone rubber such as polydimethylsiloxane (PDMS) is particularly preferred.

  In general, the thickness of the first substrate 3 is preferably in the range of 10 μm to 5 mm. When the thickness of the first substrate 3 is less than 10 μm, the portion of the material layer 11 that can be removed with a medium even at a low pressure is likely to bulge and a microchannel appears, but on the other hand, there is a risk of being easily broken. On the other hand, when the thickness of the first substrate 3 exceeds 5 mm, it is not preferable because a very high pressure is required to bulge the material layer 11 and remove it with a medium.

  The second substrate 5 in the microchannel chip 1 according to the present invention does not necessarily have elasticity and / or flexibility, but it is preferable that the second substrate 5 can be firmly bonded to the first substrate 3. This “strong adhesion” refers to an adhesive force that allows an adhesive portion other than the material layer removable by the medium to allow the channel structure to appear due to the bulging deformation of the material layer portion removable by the medium. Further, the channel structure generated by the bulging deformation of the material layer portion that can be removed by the medium can be filled with a liquid, gas, vapor, polymer or gel-like substance under pressure, and moved or handled. There is a need for adhesive strength that can withstand this pressure and handling. When the first substrate 3 is polydimethylsiloxane (PDMS), if the second substrate 5 is PDMS or glass, the first substrate 3 and the second substrate 5 are firmly bonded to each other. Can do. This phenomenon is generally called “permanent bonding”. Permanent adhesion here means that the substrate and the substrate can be bonded to each other without an adhesive only by performing some kind of surface modification on the surfaces of the substrates containing Si as components constituting the substrate. This is a property, and it is possible to exhibit a good sealing property of the fine structure in the microchannel chip. In the permanent bonding of the PDMS substrate, the bonded surfaces are appropriately subjected to surface modification treatment, and then the bonded surfaces of both substrates are closely adhered and overlapped and left for a certain period of time, whereby bonding can be easily performed. In other words, the portion where the minute gap 32 formed after removing the material layer 11 that can be removed by the medium is not permanently bonded, and is maintained in a non-bonded state, so that the balloon is deformed by pressure or the like. Thus, a gap for the flow path can appear. Further, since the portion other than the portion where the minute gap 32 exists is permanently bonded, the liquid or gas passed through the bulging portion does not leak to other portions.

  If the PDMS first substrate 3 can be permanently bonded, the second substrate 5 made of a material other than PDMS or glass can naturally be used. For example, cellulose ester base, polyester base, polycarbonate base, polystyrene base, polyolefin base, etc., specifically, polyethylene terephthalate, polyethylene naphthalate, polyethylene, polypropylene, cellophane, cellulose diacetate, cellulose acetate butyrate, cellulose acetate Propionate, cellulose acetate phthalate, cellulose triacetate, cellulose nitrate, polyvinylidene chloride, polyvinyl alcohol, ethylene vinyl alcohol, polycarbonate, norbornene resin, polymethylpentene, polyetherketone, polyimide, polyethersulfone, polyetherketoneimide, Polyamide, fluororesin, nylon, polymethyl methacrylate, acrylic Le, polyarylate and the like. Polylactic acid resin, polybutylene succinate, nitrile rubber, hydrogenated nitrile rubber, fluorine rubber, ethylene propylene rubber, chloroprene rubber, acrylic rubber, butyl rubber, urethane rubber, chlorosulfonated polyethylene rubber, epichlorohydrin rubber, natural rubber, isoprene Rubber, styrene butadiene rubber, butadiene rubber, polysulfide rubber, norbornene rubber, thermoplastic elastomer, and the like can also be used as the material for forming the second substrate 5. These materials can be used alone or in combination as appropriate.

  Furthermore, when these materials cannot be permanently bonded alone, the bonded surface is subjected to surface treatment to perform permanent bonding. The surface treatment agent is preferably a silicon compound or a titanium compound. Specifically, alkylsilanes such as dimethylsilane, tetramethylsilane, and tetraethylsilane, tetramethoxysilane, tetraethoxysilane, tetrapropoxysilane, and dimethyldiethoxysilane. Organic silicon compounds of silicon alkoxysilanes such as methyltrimethoxysilane and ethyltriethoxysilane, silicon hydrogen compounds such as monosilane and disilane, halogenated silicon compounds such as dichlorosilane, trichlorosilane and tetrachlorosilane, hexamethyldisilazane, etc. Silazane, and silicon compounds with functional groups such as vinyl, epoxy, styryl, methacryloxy, acryloxy, amino, ureido, chloropropyl, mercapto, sulfide, isocyanate, etc. And the like. These surface treatment agents can be used alone, but two or more kinds can be appropriately mixed and used.

  In general, the thickness of the second substrate 5 is preferably in the range of 300 μm to 10 mm. When the thickness of the second substrate 5 is less than 300 μm, it is difficult to maintain the mechanical strength of the entire microchannel chip 1. On the other hand, when the thickness of the second substrate 5 is more than 10 mm, the mechanical strength necessary for the microchannel chip 1 is saturated, which is only uneconomical.

  5A and 5B are a plan view and a cross-sectional view showing another embodiment of the microchannel chip according to the present invention. As shown in the drawing, a material layer 11B that can be removed with a sub medium is formed so as to intersect the material layer 11 that can be removed with the main medium. Needless to say, the above description regarding the formation method, film thickness, line width, pattern, and the like of the material layer 11 that can be removed by the medium is equally applicable to the material layer 11B that can be removed by the medium. This microchannel chip 1B is particularly suitable as a chip for cross-injection electrophoresis. For example, when it becomes necessary to use the microchannel chip 1B as an electrophoresis chip, a medium for removing the material layer 11 is fed from the port 9 toward the ports 7 and 7B, 9B, and the material layer 11 is removed, and a minute gap 32 (see FIG. 2C) to be a non-bonded portion is formed. Next, the gel electrolyte is filled from the port 9 toward the ports 7 and 7B, 9B while expanding the minute gap, and electrophoresis is performed as a microelectrophoretic path. After confirming that the gel electrolyte filled from the port 9 overflows into the ports 7 and 7B and 9B, the gel electrolyte is also filled into the ports 7 and 7B and 9B. Next, the specimen to be electrophoresed is injected into the port 7B, and the electrodes are immersed in the ports 7 and 9, 7B, 9B. First, a voltage is applied between both the ports 7B and 9B. By applying this voltage, the sample at the port 7B moves toward the port 9B and migrates in the channel generated by removing the material layer 11B. By appropriate optical detection means (not shown), the analyte is migrated to the intersection of the channel created by the removal of the material layer 11B and the channel created by the removal of the material layer 11. After confirming this, the voltage application is switched between the port 7 and port 9 electrodes. By this switching of voltage application, the sample present at the intersection migrates toward the port 9, so that a predetermined detection process can be performed in the vicinity of the port 9 by appropriate optical detection means (not shown). it can. According to the prior art, such a microchannel chip for electrophoresis has been manufactured by a complicated lithography method or the like, but according to the present invention, mass production can be performed at a low cost by the simple method as described above. Can do.

  6A, 6B and 6C are a plan view and a sectional view showing another embodiment of the microchannel chip according to the present invention. In the microchannel chip 1C in this embodiment, the substance spot layer 30 exists at a position corresponding to the material layer 11 that can be removed by the medium. The advantage of the microchannel chip 1C in this embodiment is that a material that is easily decomposed or invaded by moisture, oxygen, microorganisms, etc. in the air is sealed or shielded from these moisture, oxygen, microorganisms, etc. until just before use. It can be safely stored or protected. In addition, the microchannel chip 1C of the present invention is easy to move in a conventional rectangular channel due to an impact applied to the chip, a change in environmental pressure, or the like, and it is difficult to keep the material at a predetermined position in the channel. It can be protected from wind pressure and external impact, and can be kept in place until just before use.

  In FIG. 6A, FIG. 6B, and FIG. 6C, not only one material spot layer 30 but a desired number may exist. In addition, the substance spot layer 30 exists not only at a position corresponding to the material layer 11 that can be removed by the medium, but also at a position corresponding to the enlarged region 24 to be a liquid reservoir portion as shown in FIGS. 4A and 4B. Can be made. The material spot layer 30 can be formed on the second substrate 5 side. As shown in FIG. 6C, after the material layer 11 is removed by the medium, the material spot layer 30 is left on the upper surface of the second substrate. However, it is not limited to this aspect. The material spot layer 30 can also be provided on the first substrate 3 side. When the second substrate 5 is made of glass, the material spot layer 30 can be formed on the upper surface of the glass substrate, and the material layer 11 that can be removed with a medium can be provided on the lower surface side of the first substrate 3.

  As a material for forming the substance spot layer 30, any liquid or solid material can be used. In the case of a liquid, it can be used as it is, but it can also be applied and dried to form a film. Such materials include, for example, chemical reaction reagents, solutes, salts, saccharides, antigens, antibodies, physiologically active substances, endocrine disrupting substances, sugar chains, glycoproteins, peptides, proteins, amino acids, DNAs RNAs, microorganisms, yeasts, fungi, spores, plant fragment tissues, animal fragment tissues, drugs, glass particles, resin particles, magnetic particles, metal particles, polymers, swelling gels, solidified gels, etc. Can do. These materials can be used alone or in combination of two or more.

  Therefore, the substance spot layer 30 can be, for example, an oligomer for PCR amplification reaction (that is, a primer for PCR), or antigens or antibodies in an antigen-antibody reaction or enzyme immunoassay (ELISA) method. You can also There are two types of ELISA methods, a direct adsorption method and a sandwich method. In the case of the direct adsorption method, an antigen 30 (for example, HIV antigen) is applied to the solid phase surface of the glass substrate 5, for example, an amino coupling method, It can be attached by a method such as a surface thiol coupling method or a ligand thiol coupling method. In the sandwich method, a primary antibody can be bound to the solid surface of the glass substrate 5 instead of the antigen. In the case of the direct adsorption method, a test sample (for example, serum) is injected from the port 7. If an antibody (eg, an anti-HIV antibody) is present in the sample, it reacts with and binds to the antigen 30. Thereafter, an antigen-antibody reaction can be confirmed by injecting a coloring reagent or the like from the port 7. In the case of the sandwich method, when a solution containing a target substance (for example, protein) is injected from the port 7, the antigen in the solution is bound to the primary antibody on the glass substrate 5 by “antigen-antibody reaction”. Thereafter, an enzyme-labeled secondary antibody is injected from the port 7, and the target substance bound to the primary antibody can be qualitatively and quantitatively determined. Further, when the material spot layer 30 is made of, for example, magnetic particles, a test sample is injected from the port 7. If there is DNA in the sample, the DNA is adsorbed on the magnetic particles. Thereafter, if the magnetic particles are washed with an appropriate eluent, only the target DNA can be separated.

The material spot layer 30 can be applied and formed manually, or can be formed by an automatic application apparatus. As the automatic coating apparatus, for example, a fully automatic microarrayer (for example, Proteogen CM-1000) commercially available from Hitachi High-Technologies Corporation can be used. A feature of this apparatus is that an immobilization reagent called “prolinker” is fixed in advance on the glass substrate in order to attach the antigen on the glass substrate. According to this apparatus, chemical reaction reagents are automatically applied using a standard format glass slide of 25.4 mm × 76.2 mm with a spot diameter of 100 to 300 μm, a spot pitch of 10 μm, and a spot density of up to 4900 spots / cm ^2. Can do. When the material spot layer 30 is made of solids, the solids are suspended in a suitable solvent or the like, and the suspension is applied on a glass substrate and fixed by performing a drying treatment as necessary. Can be made. Needless to say, the substance spot layer 30 should not be removed together with the material layer 11 by a medium for removing the material layer 11.

  FIG. 7A is a schematic sectional view showing another embodiment of the microchannel chip according to the present invention. The microchannel chip 1D in the illustrated embodiment has a hollow microchannel 104 created by a lithography method using a conventional mold, and is removed by a medium so as to divide or connect the hollow microchannel 104. A possible material layer 11 is arranged.

  FIG. 7B is a microchannel chip 1D in FIG. 7A, in which only a non-adhered minute gap formed by removing the material layer 11 that can be removed by the medium slightly bulges to generate a void 18. As a result, it is a partial schematic cross-sectional view showing a state where the hollow microchannels 104 are communicated with each other on both sides of the material layer 11 that can be removed with a medium. An adapter 14 is disposed at the opening of the port 7 to be a liquid or gas introduction section, and an inlet tube 16 is connected to the adapter 14. When the medium for removing the material layer 11 is fed from the feeding tube 16, the material layer 11 is removed. As a result, the portion where the material layer 11 was present corresponds to the film thickness of the material layer 11. A minute gap in a non-adhered state is generated. When a gas such as air is pressurized and fed from the port 7, the minute gap portion bulges and a void 18 is generated, and as a result, the hollow microchannels 104 at both ends of the minute gap are communicated. Therefore, according to this embodiment, the minute gap generated as a result of the removal of the material layer 11 can function not only as a microchannel itself, but also between opening and closing between hollow microchannels produced by a conventional photolithography method. It can also serve as a valve or microvalve.

(1) Production of microchannel chip A mask was prepared in which engraved lines having a line width of 400 μm were formed in an L shape on the surface of a PET film having a thickness of 0.025 mm. This mask was placed on the top surface of a PDMS second substrate having a thickness of 3 mm and adhered to the PDMS second substrate by self-adsorption. From the upper surface of this laminate, starch having a particle size of 10 μm or less was roll-coated. As a result, a starch thin film pattern having a thickness of 10 μm was formed in an L shape on the upper surface of the second PDMS substrate. This thin film pattern is a portion to be a material layer removable by the medium. The upper surface side of the second substrate made of PDMS on which the starch thin film pattern is formed, and the lower surface side of the first substrate made of silicone rubber having a thickness of 0.1 mm having a port through hole with an inner diameter of 2 mm at a predetermined position, Surface modification treatment was performed with oxygen plasma in a plasma discharge treatment apparatus. After the treatment, when the lower surface side of the first silicone rubber substrate is bonded to the upper surface side of the PDMS second substrate on which the starch thin film pattern is formed, the PDMS second substrate and the silicone rubber first substrate are bonded together. The substrate was permanently bonded. A rectangular adapter with a thickness of 5 mm having a through hole with an inner diameter of 2 mm was subjected to the same surface modification treatment as described above and then permanently bonded to the port portion of the first silicone rubber substrate.
(2) Starch thin film removal Water was injected under pressure from one port. Water discharged from the other port was collected and iodine water was dropped. As a result, starch was detected. After this inspection was continued for a while, starch was no longer detected. At this point, it was determined that the material layer 11 made of starch was removed. Furthermore, dry air was sent in and the portion where the material layer 11 was present was dried.
(2) Liquid feeding test In the microchannel chip produced in the above (1), it was tested whether liquid could be fed from one port to the other port. 1 μL of Cyber Green I, which is a DNA staining solution, was placed on the port 9 side, and the presence or absence of fluorescence was observed with a microscope. At this point, no fluorescence was observed due to the absence of DNA. 10 μL of human genome (DNA) solution dissolved in TE was placed on the port 7 side, a syringe was connected to the through-hole of the adapter, and air pressure (positive pressure) was applied to the solution in the port 7. When the pressure is gradually increased, when the pressure exceeds 50 kPa, the non-adhesive portion composed of the minute gap 32 bulges to generate a void that should function as a microchannel, and the solution on the port 7 side moves to the port 9 side. The solution was fed and the DNA solution was mixed with a fluorescent reagent. When observed under a fluorescent microscope, it was observed that the fluorescent reagent intercalated with DNA was emitting fluorescence. Thereby, it was proved that the non-adhesion part which consists of the micro clearance gap 32 produced after removing the material layer 11 can function as a microchannel.

  The preferred embodiments of the microchannel chip of the present invention have been specifically described above, but the present invention is not limited to the disclosed embodiments, and various modifications can be made. For example, by forming the material layer 11 that can be removed with a medium in the shape of a grid and using it in combination with a mechanism that presses, closes, and seals each intersection, a number of channel liquids can be fed. Further, by stacking a plurality of substrates having the material layer 11 that can be removed by a medium, three-dimensional vertical liquid feeding is also possible.

  According to the present invention, since the microchannel chip can be manufactured very easily and inexpensively, its practicality and economy are greatly improved. As a result, the microchannel chip of the present invention can be suitably used effectively in various fields such as medicine, veterinary medicine, dentistry, pharmacy, life science, food, agriculture, fisheries, and police examination. In particular, the microchannel chip of the present invention is an optimal microchannel chip for fluorescent antibody method, in situ hybridization, etc., such as immunological disease test, cell culture, virus fixation, pathological test, cytology, biopsy histology, blood It can be used inexpensively in a wide range of areas such as inspection, bacterial inspection, protein analysis, DNA analysis, and RNA analysis.

  Further, according to the channel manufacturing method described here, when the removable material layer is removed by a medium, the wall surface in the channel becomes the surface of the bonded substrate. In a chemical reaction in which the upper surface and the lower surface in the channel are desirably made of the same material, the microchannel chip manufactured by this method is effective. In addition to the material layer removal method using this medium, to form the upper and lower surfaces in the channel with the same material, carbon, hexagonal system, and six-membered ring are used as material layers, and the bonded surface of the upper and lower substrates is plasma. Paste after processing. When air is pressurized and injected from a port that opens toward the atmosphere, the material layer itself is cleaved in the horizontal direction, not the bonded portion between the material layer and the substrate, and is divided into two. Therefore, when the pressure is further increased, the channel bulges at the cleavage plane and a channel can be formed. At this time, it is possible to form a state in which the upper and lower surfaces in the channel are covered with the same material layer.

It is a general | schematic top view of an example of the microchannel chip | tip by this invention. It is sectional drawing along the 1B-1B line | wire in FIG. 1A. It is a partial outline sectional view showing an example of a use form of a microchannel chip of the present invention. 2B is a partial schematic cross-sectional view showing a state where the material layer 11 is removed with a medium in the microchannel chip in FIG. 2A. FIG. FIG. 2B is a partial schematic cross-sectional view showing a state in which a minute gap in a non-adhered state is generated at a position where the material layer 11 was present as a result of removing the material layer 11 with a medium as shown in FIG. 2B. It is a partial outline sectional view showing the state where the minute gap shown in Drawing 2C was expanded and channel 18 was expressed. It is process drawing explaining an example of the manufacturing method of the microchannel chip | tip of a certain embodiment of this invention. It is process drawing explaining an example of the manufacturing method of the microchannel chip of another embodiment of this invention. FIG. 4B is a process diagram illustrating a subsequent process of the manufacturing method of the microchannel chip of another embodiment of the present invention shown in FIG. 4A. It is a general | schematic top view of another embodiment of the microchannel chip | tip by this invention. It is sectional drawing which followed the 5B-5B line | wire in FIG. 5A. It is a general | schematic top view of the other embodiment of the microchannel chip by this invention. FIG. 6B is a cross-sectional view taken along line 6B-6B in FIG. 6A. FIG. 6B is a partial schematic cross-sectional view showing an example of a usage pattern of the microchannel chip of the present invention shown in FIG. It is a general | schematic top view of the other embodiment of the microchannel chip by this invention. In the microchannel chip 1D in FIG. 7A, only the non-adhered minute gap portion after removing the material layer 11 that can be removed by the medium slightly bulges to generate a void 18, and as a result, the non-adhered state. It is a partial outline sectional view showing the state where hollow channel 104 was connected on both sides of a minute gap. It is an outline top view of an example of the conventional microchannel chip. It is sectional drawing which followed the 8B-8B line | wire in FIG. 8A. It is process drawing explaining an example of the conventional manufacturing method of the microchannel chip | tip shown by FIG. 8A and 8B.

Explanation of symbols

1, 1A, 1B, 1C Micro-channel chip according to the present invention 3 First substrate 5 Second substrate 7, 7A, 7B, 9, 9A, 9B Port
11, 11A Material layer removable by medium 14 Adapter 16 Inlet tube 18 Void 19 Water (medium)
20, 20A Mask 22 Through hole 24 Enlarged region layer 26 Through hole 28 PDMS sheet 30 Chemical reaction reagent spot layer 32 Micro gap

Claims (15)

In the microchannel chip, which is composed of at least a first substrate and a second substrate, and the first substrate and the second substrate are bonded to each other, at least one of the substrates on the bonding surface side, A microchannel chip in which a material layer removable by a medium is formed, and at least one end of the material layer removable by the medium is connected to a port opening toward the atmosphere. The material layer removable by the medium further includes at least one enlarged region layer having at least one planar shape selected from the group consisting of a circle, an ellipse, a rectangle and a polygon in the middle thereof. The microchannel chip according to claim 1. 2. The microchannel chip according to claim 1, wherein the material layers removable by the medium are crossed. 4. The microchannel chip according to claim 1, wherein a material layer removable by a medium is formed on the bonding surface side of the second substrate, and a port is formed on the first substrate side. . 4. The microchannel according to claim 1, wherein the material layer removable by the medium is formed on the bonding surface side of the first substrate, and the port is formed on the first substrate side. Chip. The material layer removable by the medium is formed on both the bonding surface side of the first substrate and the bonding surface side of the second substrate, and the port is formed on the first substrate side. The microchannel chip according to 1, 2, or 3. 2. The microchannel chip according to claim 1, wherein a substance spot layer is further formed at a position corresponding to the material layer removable by the medium. The microchannel chip according to claim 7, wherein the substance spot layer is formed at a position corresponding to a material layer removable by the medium and on a substrate side where the material layer is not provided. The substance spot layer includes chemical reaction reagents, solutes, salts, saccharides, antigens, antibodies, physiologically active substances, endocrine disrupting substances, sugar chains, glycoproteins, peptides, proteins, amino acids, DNAs, Selected from the group consisting of RNAs, microorganisms, yeasts, fungi, spores, plant fragment tissues, animal fragment tissues, drugs, glass particles, resin particles, magnetic particles, metal particles, polymers, swollen gels and solidified gels The microchannel chip according to claim 7, wherein the microchannel chip is formed from at least one kind of substance. The microchannel chip according to claim 1, wherein the first substrate is made of polydimethylsiloxane (PDMS), and the second substrate is made of polydimethylsiloxane (PDMS) or glass. The method for manufacturing a microchannel chip according to any one of claims 1 to 10, wherein a material removable by a medium is coated or deposited on an adhesive surface side of at least one substrate according to a desired pattern. The manufacturing method of the microchannel chip | tip which becomes. The material layer removable by the medium is formed of a material mainly composed of a powder having a particle size of 10 μm or less selected from the group consisting of water-soluble, water-insoluble, organic solvent-soluble and organic solvent-insoluble. The method for producing a microchannel chip according to claim 11. The microchannel chip according to claim 11, wherein the coating or deposition of the material removable by the medium is performed by any means selected from the group consisting of application, spraying, and printing of the material. Method. It consists of at least a first substrate and a second substrate, and the first substrate and the second substrate are bonded to each other, and can be removed by at least one medium on the bonding surface side of at least one of the substrates. A method of using a microchannel chip in which a material layer is formed and at least one end of the material layer removable by the medium is connected to a port that opens to the atmosphere,
The material layer is removed by feeding a medium from one port, a non-adhesive minute gap is generated at a location where the material layer was present, and a positive pressure is applied from the port. A method of using a micro-channel chip, comprising using a microchannel with or without swelling a gap. A method for using a microchannel chip, wherein the medium for removing the material layer is liquid or gas.

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