JP6372254B2 - Manufacturing method of microchannel chip - Google Patents

Description

  The present invention relates to a method for manufacturing a microchannel chip. More specifically, the present invention relates to a method for manufacturing a microchannel chip having an electrode portion.

  In recent years, in the field of the chemical industry (particularly, the pharmaceutical industry related to the manufacture of pharmaceuticals, reagents, etc.), development of microchannel devices using microcontainers called micromixers or microreactors has been promoted. A microchannel device is provided with a plurality of microchannels (microspaces or microcavities connected to microchannels), and a plurality of types of fluids are merged in the microspace through the microchannels. Mix fluids or cause chemical reactions with mixing.

  Japanese Patent Laying-Open No. 2008-249346 (Patent Document 1) describes a method of manufacturing a microchannel chip having electrodes. Specifically, this manufacturing method includes a step of patterning a hot melt adhesive on one substrate by screen printing to form a fine channel which is a portion where the hot melt adhesive does not exist, and the other substrate. A process of forming an electrode corresponding to the fine flow path by ion plating, and a process of aligning and superposing the electrodes so that the fine flow path and the electrode formed on one substrate and the other substrate face each other And bonding the two substrates by thermocompression bonding.

JP 2008-249346 A

  However, the method of Patent Document 1 joins one substrate and the other substrate (electrode substrate) by dissolving a hot-melt adhesive layer provided on one substrate. Therefore, it cannot be applied to a substrate in which a channel groove is formed in advance, and it cannot be bonded without using an adhesive.

  An object of the present invention is to provide a method of manufacturing a microchannel chip using a substrate having a channel groove and without using an adhesive.

(1)
The manufacturing method of the microchannel chip of the present invention includes a step of welding an electrode sheet and a plate-like substrate. The electrode sheet is made of resin, has an electrode portion on one surface, and is treated with a solvent. The plate-like substrate is made of resin and has a flow channel on one surface. In the step of welding the electrode sheet and the plate-like substrate, the electrode sheet is laminated and welded so that the one surface of the electrode sheet and the one surface of the substrate are in contact with each other.

  With this configuration, excellent weldability between the electrode sheet and the substrate can be obtained. This is presumably due to the fact that the electrode sheet is treated with a solvent, the resin portion of the electrode sheet is swollen by the solvent, the molecules are easy to move, and the adhesion to the substrate is good. Therefore, the electrode sheet and the substrate are firmly bonded, and liquid leakage due to poor welding can be prevented. For example, when the electrode sheet to be bonded and the substrate are made of different resins, or even if they are made of the same resin, they can be easily welded when the surface condition, additives, molecular weight, etc. are different. Although it may not be, it becomes possible to weld easily by the method of this invention.

(2)
In the welding step of the electrode sheet and the substrate, it is preferable to laminate a protective sheet on the other surface of the electrode sheet and to sandwich the laminate of the protective sheet, the electrode sheet, and the substrate.

  In this case, a microchannel chip having particularly excellent transparency can be obtained.

(3)
The solvent for treating the electrode sheet is preferably a lower alcohol having 3 to 5 carbon atoms.

  Thereby, while ensuring the transparency of the microchannel chip, it is possible to preferably obtain the effect of improving the weldability.

(4)
The thickness of the protective sheet may be 10 μm or more and 50 μm or less.

  The thickness of the protective sheet is preferably 10 μm or more from the viewpoint of the transparency of the microchannel chip, and is preferably 50 μm or less from the viewpoint of energy transmission for welding.

(5)
The surface of the protective sheet that contacts the electrode sheet preferably has an adhesiveness of 0.005 N / cm or more and 0.50 N / cm or less.

It is preferable that the adhesiveness is 0.005 N / cm or more from the viewpoint of excellent adhesiveness to the electrode sheet, and 0.50 N / cm or less is preferable from the viewpoint of releasability from the electrode sheet.
In addition, the above-mentioned adhesiveness is a measured value obtained based on JISZ0237.

(6)
The base material of the protective sheet may be selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and polyethylene terephthalate.

  Thereby, the transparency of the microchannel chip can be preferably ensured.

(7)
The resin constituting the substrate may be selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and polyethylene terephthalate.

Thereby, the transparency of the microchannel chip can be preferably ensured.
(8)

  The resin constituting the electrode sheet may be selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and polyethylene terephthalate.

  Thereby, the transparency of the microchannel chip can be preferably ensured.

(9)
The microchannel chip of the present invention is manufactured by the microchannel chip manufacturing method of any one of (1) to (8).

  With this configuration, the microchannel chip is provided in which the electrode sheet and the substrate are firmly bonded together by welding, and liquid leakage due to poor welding is prevented.

It is typical explanatory drawing of an example of the manufacturing method of the microchannel chip | tip of this invention. It is a typical sectional view of a micro channel chip obtained by a manufacturing method of a micro channel chip of the present invention. FIG. 3 is a schematic top view of a microchannel chip obtained by the method for manufacturing a microchannel chip of the present invention. 2 is a photograph of a part of the surface of a microchannel chip obtained in Example 1. FIG. 4 is a photograph of a part of the surface of a microchannel chip obtained in Example 2.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings. In the following description, the same elements are denoted by the same reference numerals, and their names and functions are also the same. Therefore, detailed description thereof will not be repeated.

  In FIG. 1, an example of the manufacturing method of the microchannel chip | tip of this invention is shown with typical explanatory drawing. In FIG. 1, each element is schematically shown in a sectional view. For convenience of explaining the relative directions or positions of the illustrated elements, the upper side of the drawing is described as upper and the lower side is described as lower for each element. However, the absolute positional relationship at the time of manufacture and use is not necessarily indicated. It is not a thing (the same applies to the following figures). FIG. 2 is a schematic cross-sectional view of the microchannel chip obtained by the method of FIG. FIG. 3 schematically shows some examples of microchannel chips that can be manufactured by the method of FIG. 1 in a top view.

  As shown in FIG. 1, in the present embodiment, the plate substrate 110 and the electrode sheet 120 are sandwiched between the hot press machines 300 with the protective sheet 200 interposed on the electrode sheet 120 side. The protective sheet 200 is not an essential element. An adhesive layer is not interposed between the plate substrate 110 and the electrode sheet 120.

  The plate substrate 110, the electrode sheet 120, and the laminate of the protective sheet 200 are sandwiched by a hot press 300 to weld the plate substrate 110 and the electrode sheet 120 to obtain the microchannel chip 100 shown in FIG. . The protective sheet 200 is peeled after the microchannel chip 100 is manufactured.

  The plate-like substrate 110 is provided with a channel groove 116 on one surface 112. The plate-like substrate 110 having the flow channel 116 may be manufactured by any method, for example, may be manufactured by injection molding, or the flow channel is cut in the resin substrate. It may be manufactured by processing. In particular, the method of producing by injection molding is preferable from the viewpoint of productivity, and further, since a fine concave shape is formed by the weld line generated on the surface, it is easier to enjoy the effect of the present invention having a high joining effect. A part of the channel groove 116 penetrates to the opposite surface 111 to form a port 115.

The shape of the flow channel 116 is not limited to the illustrated shape. For example, a plurality of flow channel grooves 116 may be provided in series or in parallel, or the flow channel grooves 116 may have branches.
For example, the channel groove 116 may have a width of 1 mm or less and a depth of 0.01 mm or more and 0.5 mm or less. As a result, experiments on a minute scale can be performed.

  Those skilled in the art can appropriately select the resin constituting the plate-like substrate 110 having heat resistance to the hot press machine 300. Furthermore, from the viewpoint of ensuring the transparency of the microchannel chip 100, a highly transparent resin is preferable. For example, it may be selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and polyethylene terephthalate.

  The external shape and size of the plate-like substrate 110 can be appropriately determined by a person skilled in the art in consideration of ease of handling or analytical suitability (suitability to an analysis method and an analysis apparatus). For example, in the case of a quadrangle (square or rectangular), for example, the side is 10 mm to 200 mm, preferably 10 mm to 100 mm. The outer shape of the plate-like substrate 110 may be other polygons, circles, ellipses, and the like.

  As shown in FIG. 1, the one surface 121 of the electrode sheet 120 is laminated on the one surface 112 of the plate-like substrate 110 where the flow channel groove 116 is provided. The electrode sheet 120 is provided with an electrode portion 125 for energizing the resin sheet on one surface 121. An electrical signal can be taken out of the microchannel chip 100 by the electrode portion 125.

The electrode part 125 may be formed by adhesion or vapor deposition of a thin film on a resin sheet.
Specifically, the electrode part 125 may be selected from metal and carbon. As the metal, a metal having high conductivity and easy to form a thin film or suitable for vapor deposition is appropriately selected. For example, gold, silver, platinum, copper, etc. are mentioned. Carbon is preferable in terms of handling properties, vapor deposition properties, printability, and cost.

  The thickness of the electrode part 125 is preferably 0.001 mm or more and 0.2 mm or less. By being above the lower limit value, it is easy to maintain a thin film state, and by being below the upper limit value, a gap is less likely to occur between the plate-like substrate 110.

  The pattern shape of the electrode part 125 is not particularly limited. Further, the relative positional relationship with the flow channel 116 is not limited. For example, the electrode part 125 may be formed so as to cover the flow channel groove 116 as shown in FIG. 3A, or the electrode part 125 does not cover the flow channel groove 116 as shown in FIG. It may be formed independently at a place, or may be formed so that a part of the electrode part 125 covers a part of the flow channel 116 as shown in FIG.

  The resin sheet constituting the electrode sheet 120 may be selected from, for example, polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, polyethylene terephthalate, and the like.

  The resin that forms the resin sheet and the resin that forms the plate-like substrate 110 may be a combination that causes poor bonding when solvent treatment (described later) is not performed. In this case, it is easier to enjoy the effect of the present invention having a high bonding effect. For example, the resin constituting the resin sheet may be a resin different from the plate substrate 110.

  The film thickness of the electrode sheet 120 is 0.01 mm or more and 1 mm or less, for example. By being above the lower limit value, wrinkles and the like are hardly generated at the time of joining, and the flow channel groove 116 can be sufficiently sealed, and by being below the upper limit value, the unevenness of the plate-like substrate 110 is excellent. Followability can be obtained.

  The electrode sheet 120 is treated with a solvent. Thereby, the solvent used for the treatment remains in the resin constituting the resin sheet. The solvent is present in a state where the resin constituting the resin sheet is swollen at the molecular level. Thus, the resin molecules constituting the resin sheet are easily moved by the remaining solvent, and the adhesion to the plate-like substrate 110 is improved. Therefore, the electrode sheet and the substrate are firmly bonded together by the estimation mechanism, and liquid leakage due to poor welding can be prevented.

  The solvent treatment may be any treatment for bringing the surface of the electrode sheet 120 into contact with the solvent. For example, after patterning the electrode part 125 on the resin sheet, a process of washing the front and back surfaces of the electrode sheet 120 with a solvent may be used.

  In the solvent treatment, the time during which the electrode sheet 120 is in contact with the solvent is, for example, not less than 5 minutes and not more than 50 minutes. By being more than the lower limit, it is possible to obtain an appropriate cleaning effect and an appropriate swollen state. By being below the upper limit, excessive swelling can be prevented, and undesired burying of the plate-like substrate 110 in the flow channel 116 and blockage of the flow channel can be prevented. The external environmental conditions in the solvent treatment may vary depending on the solvent used, but are, for example, 40 ° C. or higher and 90 ° C. or lower at normal pressure.

The electrode sheet 120 after the solvent treatment may be sufficiently dried as long as the remaining state of the solvent is ensured. The drying process may be any of natural drying, vacuum drying, and heat drying. More specifically, for example, the surface solvent can be blown away with an air gun.

  Any solvent may be used as long as it is not corrosive to the resin sheet of the electrode sheet 120 and the plate-like substrate 110. Examples thereof include lower alcohols having 3 to 5 carbon atoms. More specifically, 1-propanol, isopropyl alcohol, 1-butanol, 1-pentanol and the like can be mentioned. In addition, the solvent may be ketones or alkanes.

  The protective sheet 200 is appropriately interposed between the electrode sheet 120 and the hot press machine 300, thereby preventing the electrode sheet 120 from coming into contact with the hot press machine 300, and a solvent present in the electrode sheet 120. It can have the function of accepting Thereby, good transparency of the microchannel chip 100 can be ensured. From such a viewpoint, the resin constituting the protective sheet 200 is selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and polyethylene terephthalate, for example.

  The thickness of the protective sheet 200 is, for example, 10 μm or more and 100 μm or less, preferably 15 μm or more and 50 μm or less. By being above the lower limit value, it is possible to protect from direct heat conduction by the hot press machine 300, and it is possible to satisfactorily accept the solvent present in the electrode sheet 120, and below the upper limit value. By being, heat by the hot press 300 can be preferably conducted and good weldability can be obtained.

  The surface 211 where the protective sheet 200 is in contact with the electrode sheet 120 preferably has adhesiveness. The adhesiveness is, for example, 0.005 N / cm or more and 0.50 N / cm or less, preferably 0.005 N / cm or more and 0.25 N / cm or less. By being more than the said lower limit, it is excellent in the adhesiveness to the electrode sheet 120, and by being below the said upper limit, the mold release property from the electrode sheet 120 is favorable.

  The weldability between the plate-like substrate 110 and the electrode sheet 120 can be determined by, for example, a peel test by a human hand. For example, when there is no weldability, it can be easily peeled off by human hands, and no resin remains in the welded portion. On the other hand, when there is weldability, it is preferable that the resin cannot be peeled off by human hands, or even if it can be peeled off, the resin remains in the welded portion. In this way, it is possible to determine the presence / absence and strength of weldability. By having the above weldability, good bondability between the plate-like substrate 110 and the electrode sheet 120 can be obtained.

  The welding of the plate-like substrate 110 and the electrode sheet 120 can be performed by two-stage welding of a first pressure bonding process at a low temperature and a second pressure bonding process at a high temperature. By such two-step welding, better weldability in the electrode portion 125 of the electrode sheet 120 can be obtained.

  In the first crimping step, thermocompression bonding is performed at a temperature lower than the Tg temperature of either one of the plate-like substrate 110 and the electrode sheet 120. By thermocompression bonding at such a temperature, the deformation of the channel groove 116 can be suppressed, so that the blockage and narrowing of the channel groove 116 can be prevented. Moreover, the whole resin sheet part which does not have the electrode part 125 can be welded and joined. Therefore, in the first crimping step, at least the peripheral surface of the flow channel 116 or the entire opposing surfaces of the plate substrate 110 and the electrode sheet 120 can be welded.

  In the second crimping step, thermocompression bonding is performed at a temperature higher than the higher Tg temperature of the plate-like substrate 110 and the electrode sheet 120. Thereby, the outer periphery of the electrode part 125 and the outer periphery of the plate-like substrate 110 and the electrode sheet 120 are more strongly thermocompression bonded. For this reason, the electrode part 125 periphery can be welded reliably and the leakage of the fluid from a flow path can be prevented more reliably. As the hot press machine 300, a welding type that clamps only the limited portion can be used so that the electrode portion 125 and the outer periphery of the plate-like substrate 110 and the electrode sheet 120 are subjected to thermocompression bonding.

  The difference between the temperature in the first pressure-bonding step and the temperature in the second pressure-bonding step is preferably 20 ° C. or higher and lower than 50 ° C., for example. That is, it is preferable that the temperature in the first pressure bonding step and the temperature in the second pressure bonding step are 20 ° C. or more and less than 50 ° C. across the Tg temperature of the resin. By being more than the said lower limit, the temperature of a 1st crimping | compression-bonding process becomes moderately high, the favorable weldability of the flow-path groove | channel 116 periphery can be obtained, and the 2nd crimping | compression-bonding process by being below the said upper limit. Therefore, the deformation of the channel groove 116 can be suppressed, and the narrowing and blockage of the channel groove 116 can be prevented.

  The fact that the first pressure-bonding step and the second pressure-bonding step are effectively performed can be confirmed visually or by observing interference fringes using a polarizing plate after each pressure-bonding step. Since the degree of welding differs depending on the applied temperature in the first pressure-bonding process and the second pressure-bonding process, the process management can be easily performed by observing the interference fringes at the welded portion of the resin.

Since the microchannel chip 100 obtained by the manufacturing method of the present invention is manufactured using the electrode sheet 120 subjected to the solvent treatment, the plate-like substrate 110 and the electrode sheet 120 are well welded, and the microfluidic chip 100 is obtained. It is practically sufficiently sealed so that no fluid leaks from the passage. The weldability can be confirmed by flowing 300 hPa of water, for example, from the port 115 to the fine flow path with a plunger pump or the like, and observing whether or not water leaks from the fine flow path with a microscope.
Furthermore, since the microchannel chip 100 is manufactured through the protective sheet 200 between the electrode sheet 120 and the hot press machine 300, it is excellent in transparency.

The microchannel chip 100 can be suitably used as, for example, a biochip such as a nucleic acid chip, a protein chip, an antibody chip, an aptamer chip, and a glycoprotein chip, or a microanalysis chip for various chemical analyses.

  EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples. However, the present invention is not limited to the following examples.

[Example 1]
Carbon electrodes were patterned on a polycarbonate substrate of 50 mm × 30 mm × 1.5 mm thickness having a channel groove having a width of 40 μm and a depth of 23 μm in the center of the substrate, and a sheet made of polycarbonate (of a different model number from the substrate). An electrode sheet was prepared. The carbon electrode of the electrode sheet is patterned at a position that does not cover the flow path groove of the substrate during lamination. The electrode sheet was washed with isopropyl alcohol at a high temperature (60 ° C.) for 60 minutes, and then the surface isopropyl alcohol was removed by air blowing.

  A solvent-treated electrode sheet and a substrate were laminated and thermocompression bonded at a pressure of 2000 N to prepare a microchannel chip. The thermocompression bonding was performed at 120 ° C. in the first pressure bonding process and 150 ° C. in the second pressure bonding process.

  In the prepared microchannel chip, the electrode sheet and the substrate were firmly welded. FIG. 4 shows a photograph of a part of the surface of the produced microchannel chip. The white turbidity on the surface is recognized as an evaporation trace of isopropyl alcohol used for cleaning the electrode sheet. When colored water of 138 kPa was caused to flow through the fine flow path of this micro flow path chip, the colored water flowed as designed and no leakage was confirmed.

[Comparative Example 1]
A microchannel chip was prepared in the same manner as in Example 1 except that the electrode sheet was not washed with isopropyl alcohol.
As for the produced microchannel chip | tip, peeling of an electrode sheet and a board | substrate was confirmed.

[Example 2]
A micro-channel as in Example 1, except that a protective film made of polymethylmethacrylate was attached to the electrode sheet-substrate laminate treated with the solvent, on the opposite side of the electrode sheet from the substrate. Created a chip. As the protective sheet, those having thicknesses of 20 μm, 40 μm, and 50 μm were used, and microchannel chips were similarly prepared. Each of the protective sheets had an adhesiveness on the surface in contact with the electrode sheet, and the adhesiveness was 0.01 N / cm (based on JIS Z0237).
The same protective sheet was used throughout the first pressure-bonding process and the second pressure-bonding process.

  A photograph of a part of the surface of the prepared microchannel chip is shown in FIG. According to this example, by using the protective film, the cloudiness confirmed in Example 1 was not confirmed, and a microchannel chip excellent in transparency was obtained. Such good transparency was confirmed in the case of protective sheets of any thickness.

[Correspondence Relationship Between Each Part in Embodiment and Each Component in Claim]
In the present invention, the microchannel chip 100 corresponds to a “microchannel chip”, the plate-like substrate 110 corresponds to a (substrate) “substrate”, and the surface 112 (of the substrate) “one surface”. The electrode groove 120 corresponds to the “channel groove”, the electrode sheet 120 corresponds to the “electrode sheet”, the surface 121 corresponds to “one surface” (the electrode sheet), and the electrode portion 125. Corresponds to the “electrode part”, the protective sheet 200 corresponds to the “protective sheet”, and the surface 211 corresponds to the “surface” in contact with the electrode sheet of the protective sheet.

  Preferred embodiments of the present invention are as described above, but the present invention is not limited to them, and various other embodiments are possible without departing from the spirit and scope of the present invention. Furthermore, the operations and effects described in this embodiment are merely examples, and do not limit the present invention.

DESCRIPTION OF SYMBOLS 100 Microchannel chip | tip 110 Plate-shaped board | substrate 112 One side of 116 (plate-shaped board | substrate) 116 Channel groove | channel 120 Electrode sheet 121 (One side of electrode sheet) 125 Electrode part 200 Protection sheet 211 (Contacts the electrode sheet of a protection sheet )surface

Claims (6)

A resin electrode sheet provided with an electrode portion on one surface, which is treated with a solvent, and a resin plate substrate having a channel groove on one surface, the one surface stacked so are in contact with each other only contains the welding process of welding,
The electrode sheet is composed of a resin selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and polyethylene terephthalate,
The solvent includes a lower alcohol selected from the group consisting of 1-propanol, isopropyl alcohol, 1-butanol, and 1-pentanol,
The method further includes a step of laminating a protective sheet on the other surface of the electrode sheet, and the surface of the protective sheet that contacts the electrode sheet has an adhesive property of 0.005 N / cm or more and 0.50 N / cm or less. Road chip manufacturing method. In the welding step, the laminated electrode sheets other of said the surface protective sheet of the protective sheet, by nipping the laminate of the electrode sheet and the substrate, welding the said substrate and the electrode sheet, The method for producing a microchannel chip according to claim 1. The manufacturing method of the microchannel chip according to claim 1 or 2 whose thickness of said protection sheet is 10 micrometers or more and 50 micrometers or less. Base material of the protective sheet, polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate is selected from the group consisting of polyethylene terephthalate, to any one of claims 1 3 The manufacturing method of the microchannel chip | tip of description. Said substrate is a polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and a resin selected from the group consisting of polyethylene terephthalate, any one of claims 1 4 The manufacturing method of the microchannel chip | tip of description. The electrode sheet, polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and a resin selected from the group consisting of polyethylene terephthalate, one of claims 1 to 5 1 The manufacturing method of the microchannel chip | tip of description.