JP2006061870A - Membrane device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To solve such a problem that a membrane device used as a micro-chemical chip is incapable of performing bonding and causes the formation of voids on the peripheral part of membrane even after bonding when trying to put a thick separation membrane between substrates. <P>SOLUTION: The membrane device is obtained by bonding a plurality of substrates among which at least one substrate has a surface having a recessed part and the separation membrane manufactured in an outside. The separation membrane is held by one substrate among the substrates on lateral parts and a part of one side surface of the separation membrane, and the bonding surface sides of the separation membrane and the substrate are made to be the same level at least on the peripheral part of the held separation membrane. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a microchemical chip having a membrane separation mechanism, and more particularly to a method of sandwiching an externally formed film between two or more substrates, and a method for relaxing the bonding conditions.

  The microchemical chip performs various unit operations and reactions for analysis, production, and control in chemistry and biochemistry, using microfabricated chips and piping materials. In particular, development is progressing in the analytical field. Typically, a groove is carved into a glass, silicon, or resin chip surface of about 10 centimeters to several centimeters square, and a reagent solution or specimen is poured into the groove. , Separation and reaction are performed to analyze a small amount of sample. These operations and processes are realized by forming one or a plurality of functional parts on one chip (for example, see Patent Documents 1, 2, 3, or Non-Patent Document 1).

  Membrane separation technology is an important unit operation, and by providing a porous thin-film partition structure, the presence or absence of permeation is determined mainly by the size of the object, and impurities can be removed and useful substances can be concentrated and diluted. In addition, the membrane structure can be used as a catalyst carrier or reaction liquid interface in the reaction field. A wide range of separation membranes have already been developed and marketed for various applications, and their thickness is generally in the range of several micrometers to 1 millimeter.

  Separation membranes have already been incorporated into microchemical chips. A method of attaching to the outside of the chip (for example, Patent Document 4), a method of incorporating at the time of forming a resin chip (for example, Patent Document 5 or Non-Patent Document 2), and forming a film on one substrate after processing the recess And a method of sandwiching the other substrate (for example, Non-Patent Document 3), a method of forming a film in the formed microchannel (for example, Patent Document 8, Non-Patent Documents 4 and 5), and a method of using an adhesive ( For example, Patent Documents 6, 7, 8, and 9) and a method of simply sandwiching a separation membrane (for example, Patent Document 6 and Non-Patent Documents 6 and 7) are available.

JP-A-2-245655 (Claims) JP-A-3-226666 (Claims) JP-A-8-233778 (Claims) JP-A-8-114539 (Claim 15) JP 2000-202916 A (Claims 13 and 14) JP 2000-237552 A (Claims) JP 2000-237556 A (Claims) JP 2000-226871 A (Claims) JP 2003-334056 A (Claims) “Analytical Chemistry” (USA), American Chemical Society, 1997, Vol. 69, pp. 2626-2630 Proceedings of the 7th Chemistry and Micro / Nano System Study Group, Chemistry and Micro / Nano System Study Group, 2003, p. 66 Proceedings of the Electrostatic Society of Japan '00, Electrostatic Society, 2000, pp. 123-126 “Analytical Chemistry” (USA), American Chemical Society, 2003, Vol. 75, pp. 350-354 “Journal of American Chemical Society” (United States), American Chemical Society, 2002, Vol. 124, pp. 5284-5285 “Analytical Chemistry” (USA), American Chemical Society, 1998, 70, pp. 3553-3556 “Analytical Chemistry” (USA), American Chemical Society, 2003, Vol. 75, pp. 2224-2230

  The film created outside the chip has a much higher degree of freedom in film formation than the method of film formation inside the chip, and has a wide range of accumulated technologies. As described in Patent Document 9, it is difficult to arrange a membrane using an adhesive so as to divide a concave portion of one substrate into a stock solution side and a filtrate side of membrane separation. It is not preferable because the property cannot be improved. The method of simply sandwiching between two substrates can use these externally formed films. Furthermore, it conforms to the most common method for producing a microchemical chip, in which a substrate having a minute recess formed on at least one is bonded, and is the most suitable method for integration with other functional parts. .

  However, in the method of simply sandwiching the film, there is no choice but to attach a film so as to cover the entire recess of the chip or to combine a very thin film with a soft substrate. For this reason, the former cannot suppress the leakage of the separation membrane in the direction of the membrane surface, and the latter cannot combine a general separation membrane with a hard material such as glass or resin that is common in a microchemical chip. That is, the first problem is to solve the problem that when a thick separation membrane is sandwiched between substrates, bonding cannot be performed due to the film thickness, or voids are formed in the periphery of the film even after bonding. It is to be.

  The second problem is to prevent the space to be formed facing the film from collapsing due to deformation of the film, which is likely to occur because the microchemical chip is often a thin structure. Deformation factors are due to strain at the time of bonding and pressure difference when used as a separation membrane.

  The third problem is that in order to form a space on both sides of the membrane, recesses are formed in the base material on both sides to be sandwiched. The exact position of the recesses required to maintain the separation efficiency of the membrane It is to eliminate the alignment.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have formed a step structure corresponding to the thickness of the separation film on the substrate for the first problem. It has been found that it can absorb and absorb without leakage.

  Furthermore, it was found that the same effect can be obtained by holding the periphery of the membrane with another base material having the same thickness as the membrane.

  Furthermore, one of the tanks on both sides of the membrane is limited to the inside of the membrane (inside when viewed from the direction perpendicular to the membrane surface), or the periphery of the membrane is strongly suppressed or crushed with a solvent. It was found that the problem of leakage that tends to occur in the surrounding area can be avoided.

  For the second problem, it has been found that it is effective to form a support structure, and it has been found that the retention of bubbles can be easily suppressed by taking a folded flow path shape.

  In addition, for the third problem, it is found that one can be made sufficiently large with a margin than the other, or a structure that does not induce a large change in the film surface due to misalignment by orthogonally folding the flow path, The present invention has been completed.

That is, the present invention has the following configuration.
(1) A membrane device obtained by joining a plurality of base materials having a surface having at least one concave portion formed thereon and a separation membrane prepared outside, wherein the separation membrane is a side portion and one side of the separation membrane. A membrane device characterized in that a part of the surface is held by one of the substrates, and at least the separation membrane peripheral portion held by the separation membrane and the bonding surface side of the substrate are the same surface.

  (2) A membrane device obtained by joining a plurality of base materials having a surface with concave portions formed on at least one sheet and a separation membrane prepared outside, and one or both of the base materials sandwiching the separation membrane A membrane device, wherein a bonding step is performed after a recess corresponding to the thickness of the separation membrane is provided at the separation membrane arrangement position of the substrate.

  (3) A membrane device obtained by joining a plurality of base materials having a surface with at least one concave portion and an externally prepared separation membrane, the separation membrane being held around by a separate member A membrane device characterized in that the separation membrane and the holding member have the same thickness at least in the periphery of the separation membrane.

  (4) On the membrane sandwiching surface side of at least one of the two substrates sandwiching the separation membrane, the inside of the separation membrane placement position (inside from the direction perpendicular to the membrane surface, clearly not in context) The same applies to the rest of the case except that the concave portion is formed so that the base material and the separation membrane do not contact each other, and the shape of the concave portion in the surface direction is formed only inside the separation membrane. The membrane device according to any one of (1) to (3) above,

  (5) On the membrane sandwiching surface side of both base materials sandwiching the separation membrane, the base material and the separation membrane are not in contact with each other at a part of the inside of the separation membrane arrangement position, and upstream or downstream of membrane separation A concave portion used as a side tank is formed, and the shape in the surface direction of the concave portion used as a tank formed on one base material is perpendicular to the surface than the concave portion used as a tank formed on the other base material. The membrane device according to any one of the above (1) to (4), wherein the membrane device is formed inside as viewed from the side.

  (6) The membrane device as described in any one of (1) to (5) above, wherein the separation membrane has a peripheral portion with less or no permeability than the central portion.

  (7) On the membrane sandwiching surface side of at least one of the two substrates sandwiching the separation membrane, a recess is provided so that the substrate and the separation membrane do not contact at a part inside the separation membrane arrangement position. The membrane device according to any one of (1) to (6), wherein the membrane device is formed, and the shape in the surface direction of the concave portion has a convex shape on the inner side or an island shape on the inner side.

  (8) The membrane device according to any one of (1) to (7) above, wherein the shape of the concave portion in the surface direction is a folded linear shape.

  (9) A linear recess formed in the two base materials, in which the concave portion is formed on both of the two base materials sandwiching the separation membrane, the surface shape of the concave portion is folded. The film device according to any one of the above (1) to (8), wherein the line direction is formed in a direction intersecting when viewed from a direction perpendicular to the surface.

  By adopting the present invention, when a thick separation membrane is sandwiched between substrates, bonding can be performed regardless of the film thickness, and no voids are formed in the periphery of the film even after bonding. In particular, by making one film surface and the bonding surface the same surface after bonding, voids due to the film thickness can be eliminated.

  By providing the substrate with a recess corresponding to the thickness of the separation membrane, the gap after bonding due to the film thickness can be eliminated.

  Alternatively, the gap after joining can be eliminated by sandwiching the membrane with a member corresponding to the thickness of the separation membrane.

  Since the voids can be eliminated in this way, the membrane can be appropriately incorporated into the microchemical chip, and appropriate pressurization, liquid feeding, and membrane separation can be performed without causing liquid leakage.

  By adopting a membrane having little permeability at the peripheral portion, liquid leakage in the peripheral direction can be further suppressed.

  In addition, the microchemical chip often has a thin gap to be formed facing the membrane. However, even when the membrane is deformed, the space is not crushed, and bubbles can be easily removed when liquid is passed.

  By forming one tank only on the inside of the membrane, it is possible to avoid the influence of a gap that tends to remain on the side of the membrane.

  The structure of the tank is convex on the inside, or an island shape is formed on the inside, which becomes a support structure for the film, and the tank is crushed by strain after chip fabrication and pressure for membrane separation. You can avoid it.

  Further, by adopting a linear shape for this structure, liquid can be fed while appropriately removing bubbles that tend to be mixed in or suppressing diffusion before and after the reagent segment.

  Furthermore, by forming one tank on the inner side with a blank space than the other tank, it becomes possible to absorb the alignment error for the blank space. Alternatively, by arranging the folded line shapes so as to cross each other, the effective area of the film can be hardly changed even if an alignment error occurs.

  As described above, according to the present invention, it is possible to provide a microchemical chip in which various films prepared outside are introduced into only a part of the chip without causing leakage and requiring strict alignment.

The present invention will be specifically described below.
The separation membrane (hereinafter referred to as “membrane”) in the present invention refers to a structure having a surface larger than the thickness and allowing mass transfer through the surface by various driving forces. The target is fluid regardless of whether it is liquid or gas. Various modes such as general filtration, microfiltration, ultrafiltration, nanofiltration, reverse osmosis, diffusion dialysis, electrodialysis, gas separation, vapor permeation, and pervaporation can be considered as the membrane separation mode. is not. The flow direction of fluid is intended for both dead end and cross flow, but is not limited to this. The shape of the membrane is roughly classified into a flat membrane, a hollow fiber membrane, and a capsule type. However, in the present invention, only the flat membrane is an object, and the hollow fiber membrane and the capsule type are not an object. The purpose of use of the membrane is to remove unnecessary substances in the microchemical chip, concentrate and capture useful substances, and to apply to the microchemical chip other than separation by coating or collecting the useful substances before incorporation. It is possible to give functions including. Useful materials include, but are not limited to, inorganic catalysts, organic catalysts, enzymes, cells, dyes, membrane-impermeable components in environmental samples, membrane-impermeable components in body fluids, and the like. Therefore, the membrane device in the present invention can be used for purposes other than separation. For this reason, the membrane in the present invention does not necessarily need to be provided with spaces on both sides after incorporation.

  The thickness of the film is arbitrary but is preferably 1 micrometer or more, more preferably 10 micrometers or more and 3 millimeters or less. A film having a thickness of 1 micrometer or less alone has a low strength and is difficult to handle for bringing it into the bonding process after production. A film having a thickness of 10 micrometers or less is not related to the method of the present invention. In both cases, good pinching can be carried out. Moreover, it is because a film having a thickness of 3 millimeters or more is not suitable for making a minute device.

  Various materials used for the existing film can be used as the material of the film. Cellulose, regenerated cellulose, cellulose acetate, cellulose triacetate, cellulose nitrate, other cellulose derivatives, polyamide, aromatic polyamide, polyacrylonitrile, polyethylene, polypropylene, polystyrene, polyvinyl chloride, polyvinyl alcohol, polyhydroxymethacrylate, other polymethacrylate Acid derivatives, polysulfone, polyethersulfone, polycarbonate, polyethylene terephthalate, polytetrafluoroethylene, polyvinylidene fluoride, other fluororesins, copolymers thereof, other synthetic resins, glass, zeolite, other ceramics, metals and these There is a combination, but it is not limited to this. In addition, there are membranes obtained by physically treating these membrane surfaces physically, chemically and biologically, and membranes combined with a support. The present invention is a method of gently incorporating an externally created film into a microstructure regardless of its film thickness, and the film thickness difference is preliminarily processed by a recess, pressure, heat, and chemical changes to cause leakage. This is because there is no structure.

  The separation membrane prepared outside in the present invention refers to a separation membrane prepared without being brought into contact with a base material that will be in contact with the membrane after incorporation. For example, Patent Document 8 and Non-Patent Documents 3, 4, and 5 are created in a state where the separation membrane is in contact with the base material to be finally incorporated. On the other hand, for example, Non-Patent Documents 6 and 7 are incorporated after being created at a place unrelated to the base material. Creating the film outside has a very high degree of freedom in film formation as compared with a method of forming a film inside the chip, and there is a wide range of accumulated technologies.

  When the film is sandwiched between two plates having the same size as the film surface, the side part of the film refers to the part of the film exposed to the side surface and its very vicinity. In a well-cut film, it is the side surface of the film, but it does not matter whether the film is formed.

  The membrane device of the present invention is a microfluidic microchemical chip. A general microfluidic microchemical chip is manufactured by joining a plate-like base material having a concave portion to another base material. The substrate may be a sheet, plate, film, rod, tube, coating film, cylinder, or other complex shaped product, but is not limited thereto. However, from the viewpoint of workability and ease of handling, it is preferably a sheet shape, a plate shape, or a film shape. As the base material, glass, ceramics, resin, metal, semiconductor, and combinations thereof can be considered, but are not limited thereto.

  In the present invention, the surface in the plane direction refers to a bonding surface. In the case of a combination having a complicated joint surface, it indicates a target local joint surface.

  The recesses in the present invention include two types of recesses that form a space into which a fluid is introduced after bonding, and recesses for incorporating a film, which are found in typical microchemical chips. It does not prevent the formation of the concave portion used for the purpose. The concave portion into which the fluid is introduced after joining may be configured as a concave portion included in one base material that cannot be divided, or may be configured by combining a base material having a through-hole shape and another base material. A concave portion is formed only on one side of the substrate as viewed from the membrane, and a tank can be formed on the other side using deformation due to fluid filling, but when using the membrane separation function, preferably Concave portions are formed in both base materials. The combination of a base material having a through-hole shape and another base material is a mode in which, for example, the spacer shown in FIG. 1 is used. In FIG. 1, the right side is an exploded perspective view, 2 is a base material, 3 is a spacer, and 4 is a through hole formed in the spacer 3. The left side of FIG. 1 is a laminate of the base material 2 and the spacer 3, and the through hole in the spacer 3 functions as a recess provided in the base material.

  In order to obtain a recess or through-hole shape, injection molding, hot embossing, solvent casting, cutting, etching, punching, photolithography, lift-off, vapor deposition, and combinations thereof can be used as a means. It is not something.

  A typical recess of the microchemical chip, which forms a space for introducing a fluid after joining, preferably has a linear shape with a width of 1 to 500 micrometers when viewed from the direction perpendicular to the substrate, and is less than 100 square centimeters. The combination of geometric shapes is 1 to 500 micrometers in depth, but is not limited to this. Typically, the line shape becomes a tube shape after joining, and is used as a flow path, and other geometric shapes are used in a space for introducing a specific function or a space for introducing another member. For parts used as flow paths, if the width or depth is less than 1 micrometer, the pressure loss as the flow path increases, which is inappropriate. If the depth or width exceeds 500 micrometers, and the partial geometry This is because it is unsuitable for the overall size as a microdevice when the value exceeds 100 square centimeters. Moreover, it is preferable that the base material which has a through-hole shape for recessed part formation is 500 micrometers or less in thickness at the periphery of a through-hole at least. This is because the thickness of the substrate having the through hole defines the dimension in the depth direction of the space into which the fluid after joining is introduced. However, these dimensions do not define the dimensions of the space other than the flow path flowing in the surface direction at the joint surface. For example, a typical sample introduction hole is formed in a form in which a through hole is formed with a plate thickness exceeding 500 micrometers, and in a reaction vessel or an electrophoresis vessel, the width may exceed 10 mm. Good.

  The concave portion for incorporating the film is larger in the surface direction than the film to be incorporated, and has a depth corresponding to the film thickness. A recess serving as a space for the fluid is preferably formed inside the recess for incorporating the membrane.

  The microchemical chip is formed by joining a plurality of substrates. The present invention is directed to a system in which a film is sandwiched between two or more substrates, and the number of substrates in the entire microchemical chip is not limited to two.

  The term “joining” in the present invention refers to a technique in which a plurality of base materials are overlapped so that fluid leakage does not occur from a recess if necessary. More specifically, simple superposition, surface activation by plasma treatment, a method involving heating, a method of applying pressure, a method of applying an electric field, a method of using an adhesive, a method of using a solvent, and these There are combinations. Preferably, it is carried out at a temperature not exceeding 30 ° C. above the heat resistance temperature of the film. This is because if the film is heated by 30 ° C. or more from the heat-resistant temperature, the film becomes the heat-resistant temperature or more due to radiant heat or heat transfer from the bonding surface, and the film function is lost. In addition to irreversible bonding, bonding can also be performed by a pressurization method in which a jig is pressed during use.

  The plurality of substrates in the present invention refers to two or more. In the case of microchemical chips, devices with about 2 to 10 layers have already been reported, and an improvement in throughput has been proposed by combining hundreds to thousands. A plurality of base materials can be combined in the surface direction at one joint surface portion with the film to be incorporated, but each base material is preferably composed of one base material from the viewpoint of simplification of the structure and suppression of leakage. For this reason, at least two substrates are required. However, this does not preclude the combination with another substrate other than the vicinity of the film to be incorporated or other than the film incorporation surface. In claim 3 at the time of filing, since another member for holding the film is necessary, it is preferably three or more when including the other member.

  In the present invention, the same surface, corresponding thickness, or the same thickness means the position and thickness of the surface taking into account the amount of deformation after bonding, which can be known in advance by a pressure test on the film and a bonding test of the base material separately. It means that the thickness is 10 micrometers or less between the film to be compared and the base material or member. This is because a film having a thickness of 10 micrometers or less can be liquid-tightly bonded without using the method of the present invention.

  Holding in the present invention refers to a state in which a member is installed so that the membrane cannot move in that direction. The fact that the substrate holds the film on a part of the film surface means that the substrate is arranged so as to contact a part of the film on the side where the substrate is placed. Holding means that the base material is installed on the same surface in the direction away from the membrane from the periphery of the membrane.

  A film having a uniform property in the plane direction can be used, or a film having a peripheral portion with less permeability than the central portion can be used. A membrane having a lower peripheral part permeability than the central part is preferable because it has an effect of suppressing liquid leakage in the surface direction. Membranes with less permeation at the periphery than those in the center are combinations of different types of membrane materials, films formed with different permeabilities, and membranes that were originally homogeneous in the surface direction are physically and chemically There are, but are not limited to, those that have lost or lost permeability due to mechanical effects, and combinations thereof.

  The concave portion used as a tank formed on the base material in the present invention is a concave portion that forms a space into which a fluid is introduced after joining, and is located at a position where the film is disposed and is bent or the concave portion is the same. It refers to a portion that is wider or deeper than other concave portions of the surface. For example, in Non-Patent Documents 6 and 7, the membrane is disposed in a recess having the same shape as the other recesses on the same surface, and the same flow path pattern can be used in the present invention. However, when actively used as a tank, membrane separation occurs on the membrane surface, so in order to obtain a sufficient membrane area for separation, the surface direction pattern of the upstream tank and the downstream tank part of the membrane separation is It is preferably designed to form a wide membrane separation region that is wider than the characteristic channel width of the microchemical chip or by folding the channel. For example, the embodiment shown in FIG. That is, FIG. 2 shows the shape of the recesses when viewed from the direction perpendicular to the surface of the base material, and the three views (hatched) in FIG. Is shown. The left-hand side of FIG. 2 has a large circular recess formed at the end of the linear flow path, and this circular recess functions as a tank. That is, this example is an example in which the concave portion functioning as a tank is wider than the width of the flow path. 2 is an example in which the concave portion that functions as a flow path is configured in a folded line shape, the central flow path shape 5 is a comb shape, and the right flow path shape 6 is a simple folded shape. is there.

  In the present invention, the shape in the surface direction of the concave portion used as a tank formed on one base material is sufficiently inside as viewed from the direction perpendicular to the surface than the concave portion used as a tank formed on the other base material. When forming a convex shape only on the outside with a minimum area that can cover the concave portion used as a tank formed on the base material when viewed from the direction perpendicular to the surface, This means that the convex shape of the material is included in the convex shape of the other base material. In other words, when viewed from a direction perpendicular to the surface of the base material, it means that the concave portion of one base material is completely inside the concave portion of the other base material. By doing so, the membrane area contributing to the separation of the membrane separation is defined by the concave portion used as a tank on the side where the convex shape is small. When aligning two or more substrates, a margin portion is formed by the difference between the two convex shapes, and the alignment error can be absorbed by the margin portion. Thus, the difference between the larger side and the smaller side that will form the margin is preferably 1 micrometer to 10 millimeters. This is because if it is less than 1 micrometer, it does not make sense as a structure that absorbs alignment errors, and if it exceeds 10 millimeters, it is inappropriate as a micro device. More preferably, it is 0.5 mm or less. From the viewpoint of effective use of the chip area, the difference portion that does not contribute to the original membrane separation is preferably small, and the alignment accuracy has an accuracy of 0.5 mm or less in many methods. A structure portion that is a concave portion that is not used as a tank, such as a flow path for connection with other parts in the chip, is not taken into consideration when considering the convex shape. This is not necessary when considering the effective area of the membrane, and the connection flow path generally has a narrow line shape even though there is a portion in contact with the membrane, so that the influence of the alignment error is inherently small.

  On the other hand, Non-Patent Document 6 shows a method of forming a folded line shape on both of two substrates sandwiching a separation membrane, and the two line shapes share a center line when viewed from a direction perpendicular to the surface. Designed to be. However, conversely, both of the two substrates sandwiching the separation membrane have a linear shape in which the surface shape of the concave portion is folded as shown in FIG. 3, and the line direction intersects when viewed from a direction perpendicular to the surface. In this case, even if an alignment error occurs, the portion 9 effective for separating the film only moves in parallel, and its area does not change. That is, FIG. 3 is a diagram showing a linear recess (flow path) formed in the base material, and the left side of FIG. 3 shows the shape of the recess provided in one base material (upper plate flow path pattern). 7) The figure on the right shows the shape of the recess (lower plate flow path pattern 8) provided on the other substrate. “Line direction of recess” is a main direction in which a linear recess is formed. In the shape of the left side of FIG. 3, the horizontal (horizontal) direction of the page, and in the shape of the right side of FIG. The longitudinal (vertical) direction is the “line direction of the recess”. Accordingly, in the example shown in FIG. 3, the linear concave portions are formed in a direction (in this case, a direction orthogonal in particular) where the linear directions intersect with each other when viewed from a direction perpendicular to the surface. 3 in FIG. 3 indicates a region where the recesses formed in each substrate intersect (overlap) when viewed from a direction perpendicular to the surface of the substrate, and the film provided in this portion is separated. Functions as a membrane. As is apparent from the figure, even if the overlapping positions of the substrates are slightly shifted, the area 9 (overlapping area) effective as a separation film is merely moved in parallel and the area does not change.

  In the present invention, “having an inwardly convex shape” means that at least a part of the outer periphery of the shape has an inwardly convex shape. For example, the embodiment shown in FIG. That is, FIG. 4 is a diagram illustrating an example of the shape of the concave portion viewed from a direction perpendicular to the surface of the base material, and three examples are described. The hatched part is a recess. The center 6 is an example of a simple folded line shape, and the right 10 is an example of a spiral type. In FIG. 4, reference numeral 11 denotes “inwardly convex shape”, and no concave portion is formed in this portion. The size of the convex portion is preferably such that the maximum value of the diameter of the inscribed circle is less than 50% of the diameter of the circumscribed circle in the region where membrane separation occurs. In order to prevent the film from crushing the tank by this convex part, a sufficiently large convex part is necessary for the region, but even in the equilateral triangle that does not have an inwardly convex shape, it is inscribed. This is because the ratio of the circle to the circumscribed circle is 50%.

  In the present invention, having an island shape on the inner side means that a part of the inner side of the concave part is not a concave part and is not continuous with the outer side. For example, the embodiment shown in FIG. That is, FIG. 5 is a diagram illustrating an example of the shape of the concave portion viewed from a direction perpendicular to the surface of the base material, and three examples are described. The hatched part is a recess. In FIG. 5, 12 is an “island shape” formed inside the recess, and this portion is not a recess. By providing such an island shape, the film can be supported, and the film can prevent the tank from being crushed and contribute to increasing the pressure resistance of the device.

  However, since membrane separation is not performed in the convex shape on the inside or the island-shaped portion on the inside, these areas are used from the viewpoint of effectively using the area of the film to be incorporated and the area necessary for membrane incorporation in the chip. Is preferably less.

  In the present invention, the folded line shape has a line width equivalent to a line shape pattern that forms another flow path, and is exemplified by 5 and 6 in FIG. 2, and 6 and 10 in FIG. A simple fold, spiral, comb, or a combination thereof refers to a shape that covers a region that is significantly wider than the channel width by a linear shape. Preferably, it is a simple fold or comb type, more preferably a dead end type is a shape having more than one of the branch structures found in a comb shape or a comb structure, or a flow-through type using a sample forming a segment. In that case, it is a simple folding type or a spiral type without a branching structure. This is because the comb shape has a smaller pressure loss than the other shapes, and the simple folding type and the spiral type do not have a branch structure, so that dispersion in the flow direction of the sample can be suppressed.

  FIG. 6 is a cross section perpendicular to the substrate surface of a microchemical chip in which a film is incorporated after bonding in claim 1 at the time of filing or a claim dependent thereon. The bonding surface of the upper base 13 and the lower surface of the incorporated film 15 form the same surface. Reference numeral 14 denotes a lower base material, and 16 and 17 denote concave portions provided on the respective base materials, each functioning as a tank. For this implementation, it is desirable to match these two surfaces before joining as shown in FIG. However, there may be a shift in the position of the surface after taking into account the amount of change in the base material after bonding and the film thickness, which can be known in advance by a pressure test on the film and a base material bonding test. In many cases, the fluid that permeates the membrane also permeates in the surface direction of the membrane. Therefore, it is important to take measures to prevent liquid leakage from the side of the membrane. The holding of the side part in the present invention indicates that the wall structure is formed in the surface direction of the film, and it is not necessary that the side part and the base material are in contact with each other, and the gap 18 between the film and the wall structure shown in FIG. There may be.

  However, when the gap 18 exists all around the membrane, if both of the recess patterns serving as flow paths in the joint surfaces on both sides of the membrane are connected from the outside of the membrane, the upstream and downstream do not pass through the membrane. Since it is connected through a gap, at least one of the two substrates sandwiching the separation membrane, on the membrane sandwiching surface side, the substrate and the separation membrane do not contact at a part inside the separation membrane arrangement position. It is preferable to form a recess in the surface and form the recess in the surface direction only on the inner side of the separation membrane. However, a multi-layer flow path using a surface other than the bonding surface can cross the side of the film, or another flow path pattern that is not connected in the bonding surface can be formed outside the film.

  The film surface and the substrate surface can be aligned by fine processing of the substrate, addition of a chemical reagent such as a solvent, deformation or solid solution of the film or substrate by heat, polishing, etc. It is not something that can be done.

  However, preferably, as shown in FIG. 8, the recess 19 corresponding to the film thickness is processed in advance into the base material before bonding, or the peripheral portion is held by the member 20 corresponding to the film thickness as shown in FIG. To do. This is because even a thick film can be sandwiched so as not to leak regardless of the amount of thermal deformation or solid solution. More preferably, as shown in FIG. 10, the concave portion 19 that accommodates the film only in one base material is processed. This is because it is possible to reduce the cost by processing either one of the substrates.

  Hereinafter, the effects of the present invention will be described more specifically using examples.

  FIG. 11 shows a photomask pattern for the first upper plate of the fabricated film device, and FIGS. 12 and 13 show patterns only for the chip portions of the photomask for the second upper plate and for the lower plate. Using these mask patterns 21, 22, and 24, a PDMS chip was fabricated according to a general method for fabricating a PDMS chip of a microchemical chip. However, for the upper plate, after the first exposure step, the post-exposure baking step is not performed, and the same SU-8 is spin-coated again. A development step was performed. The number of rotations of the first spin coating was determined in advance by clarifying the number of rotations of about 100 micrometers by a preliminary study with a photoresist data sheet and various rotation numbers. After the pattern was transferred by PDMS, through holes were made in the sample introduction port and the discharge position of the pattern 9 having no internal structure on the upper plate, and then the FEP tube was fixed. A filtration membrane (GH Polypro, film thickness of about 110 μm, Pall) was cut out so as to be slightly smaller than the size of the first pattern on the upper plate, and used as a membrane for sandwiching. The bonded surfaces of the produced upper and lower plates were treated with an oxygen plasma treatment machine (PDC210, Yamato) for 100 W for 30 seconds, and overlapped while sandwiching the film. As a result, it was possible to perform bonding without lifting based on the film thickness. Further, the upstream tank formed by the pattern 22 was sufficiently smaller than the downstream tank formed by the pattern 24 when viewed from the direction perpendicular to the surface, and could be easily placed inside. Connect the sample outlet to a syringe pump (Model 210, KD Scientific), and insert the FEP tube on the sample inlet side into a suspension of fluorescent beads (Invitrogen) with a diameter of 2 micrometers. In the mode, the liquid was fed so as to flow from the upper plate to the lower plate in the membrane portion. When the membrane chip was observed with a stereofluorescence microscope (SZX, Olympus) and an inverted fluorescence microscope (IX71, Olympus) after a certain amount of suction, fluorescent beads could be confirmed only on the upstream side of the membrane and filtered well. Confirmed that can be done.

  Using a pattern 23 with a flow path as the photomask pattern for the second time on the upper plate, a membrane device was created in the same manner as in Example 1. Even if the alignment accuracy of the arrangement was lowered, the effective portion of the membrane was reduced. It was confirmed by actual state microscope observation that the area did not change. Moreover, the film | membrane was successfully integrated like Example 1. When the filtration function was confirmed by the same method as in Example 1, it was possible to perform filtration well. Moreover, even if the liquid flow direction was reversed, the membrane could be filtered in the same manner without crushing the downstream tank.

  An acrylic film having a thickness of 0.2 mm was cut into a large slide glass, and an 11 mm square hole was made in the center. This film was placed on the lower plate after the plasma treatment of Example 1, and two filtration membranes (GH Polypro, film thickness of about 110 μm, Pall) cut to 10 mm square were placed in the hole portion. Furthermore, another lower plate of Example 1 was used as an upper plate, and after forming through holes and plasma treatment, the device was completed. When the filtration test of the fluorescent beads was performed in the same manner as in Example 1, it was possible to perform the filtration in the suction mode without causing liquid leakage.

  A 1 mm thick acrylic plate (Delagrass A, manufactured by Asahi Kasei) was cut into a large slide glass, and a through hole was drilled in the center thereof. This plate was hot-pressed with a mold having a plate-like protrusion having a height of 100 micrometers. This cross-sectional schematic diagram is shown in FIG. When the filtration membrane used in Example 1 was placed on a stepped portion by press molding and a very small amount of methylene chloride was applied only to the peripheral portion of the membrane, the membrane adhered to the stepped portion and became a structure with almost no step. . Further, when combined with the lower plate of Example 1, the fluorescent bead suspension could be filtered from the upper plate side to the lower plate side by the suction mode.

FIG. 2 is a perspective view of a concave portion of a typical microchemical chip and an exploded perspective view of a spacer structure forming an equivalent shape. It is a figure which shows the example of the shape of the recessed part used as a tank when it sees from a direction perpendicular | vertical to the base-material surface. It is a figure which shows the example of the shape of the orthogonal flow path at the time of seeing from the direction perpendicular | vertical to the base-material surface. It is a figure which shows the example of an inwardly convex shape provided in a recessed part when it sees from the direction perpendicular | vertical to the base-material surface. It is a figure which shows the example of the shape which has an island shape inside the recessed part at the time of seeing from the direction perpendicular | vertical to the base-material surface. It is sectional drawing perpendicular | vertical to the base-material surface of the microchemical chip | tip after joining in which the film | membrane was integrated. It is sectional drawing perpendicular | vertical to the base-material surface of the upper plate of the microchemical chip in the state which arrange | positioned the film | membrane before joining. It is an exploded view of a cross section perpendicular | vertical to the base-material surface of the microchemical chip which processed the thickness part of the film | membrane into the upper board and the lower board beforehand. It is an exploded view of a cross section perpendicular | vertical to the base-material surface of the microchemical chip in which the film | membrane was integrated with the member for hold | maintaining the side part of a film | membrane which has a thickness comparable as a film | membrane. It is an exploded view of a cross section perpendicular | vertical to the base-material surface of the microchemical chip which processed the thickness part of the film | membrane beforehand only to the upper board. It is a figure which shows the photomask pattern for the upper plate 1st time of the produced film | membrane device. It is a figure which shows the chip | tip partial pattern of the photomask for the upper plate 2nd time of the produced film | membrane device. It is a figure which shows the chip | tip part pattern of the photomask for lower plates of the produced film | membrane device. It is a decomposition | disassembly schematic diagram of the cross section of the produced acrylic board.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Recessed part of typical microchemical chip 2 Base material 3 Spacer 4 Through hole provided in spacer 5 Comb-shaped channel shape 6 Simple folded linear channel 7 Upper plate channel pattern 8 Lower plate channel pattern DESCRIPTION OF SYMBOLS 9 Area | region effective for membrane separation 10 Spiral type 11 Inward convex shape 12 Inner island shape 13 Upper plate 14 Lower plate 15 Separation membrane 16 Recessed portion provided on upper plate 17 Recessed portion provided on lower plate 18 Membrane side portion A gap between the film and the film holding part by the base material 19 A concave part for holding the film 20 A member for holding the side part of the film having the same thickness as the film 21 A part used as a chip in the photomask 22 Internal structure No pattern 23 Folded line shape pattern for upper plate 24 Folded line shape pattern for lower plate 25 Drill hole 26 Step structure by hot press molding 27 Acrylic plate

Claims (9)

  A membrane device obtained by joining a plurality of base materials having a surface in which at least one concave portion is formed and a separation membrane prepared outside, the separation membrane being formed on the side and one side of the separation membrane. A membrane device characterized in that, in part, the membrane device is held by one of the substrates, and at least the separation membrane peripheral portion held by the same side is the same as the bonding surface side of the separation membrane and the substrate.   A membrane device obtained by joining a plurality of base materials having a surface in which at least one concave portion is formed and a separation membrane prepared outside, and one or both of the base materials sandwiching the separation membrane A bonding device is characterized in that a bonding step is performed after a recess corresponding to the thickness of the separation membrane is provided at the separation membrane arrangement position.   A membrane device obtained by joining a plurality of base materials having a surface in which a recess is formed on at least one sheet and a separation membrane created outside, the separation membrane being held by another member around the periphery, A membrane device characterized in that the separation membrane and the holding member have the same thickness at least in the periphery of the separation membrane.   On the membrane sandwiching surface side of at least one of the two substrates sandwiching the separation membrane, a recess is formed so that the substrate and the separation membrane do not contact each other at a part inside the separation membrane arrangement position. The membrane device according to any one of claims 1 to 3, wherein the shape of the concave portion in the surface direction is formed only inside the separation membrane.   As the membrane sandwiching surface side of both substrates sandwiching the separation membrane, the substrate and the separation membrane are not in contact with each other at a part of the inner side of the separation membrane arrangement, and as an upstream or downstream tank for membrane separation The concave portion to be used is formed, and the shape in the surface direction of the concave portion used as a tank formed on one base material is viewed from the direction perpendicular to the surface than the concave portion used as a tank formed on the other base material. The membrane device according to claim 1, wherein the membrane device is formed inside.   6. The membrane device according to any one of claims 1 to 5, wherein the separation membrane has a peripheral portion with less or no permeability than the central portion.   On the membrane sandwiching surface side of at least one of the two substrates sandwiching the separation membrane, a recess is formed so that the substrate and the separation membrane do not contact each other at a part inside the separation membrane arrangement position. The membrane device according to any one of claims 1 to 6, wherein the shape of the concave portion in the surface direction has a convex shape on the inner side or an island shape on the inner side.   The membrane device according to any one of claims 1 to 7, wherein a shape of the concave portion in a surface direction is a folded linear shape. The concave portion is formed in both of the two base materials sandwiching the separation membrane, and the surface shape of the concave portion has a folded linear shape, and the linear direction of the linear concave portion formed in the two base materials The film device according to claim 1, wherein the film device is formed in a direction intersecting when viewed from a direction perpendicular to the surface.

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