JP5788709B2 - Microchip and manufacturing method thereof - Google Patents

Description

  The present invention relates to a microchip and a manufacturing method thereof. More specifically, a microchip useful as a micro-TAS (Micro Total Analysis System) and the like suitably used for biochemical tests such as DNA, proteins, cells, immunity and blood, chemical synthesis and environmental analysis, and the production thereof Regarding the method.

  In recent years, the importance of detecting or quantifying biological substances such as DNA (Deoxyribo Nucleic Acid), enzymes, antigens, antibodies, proteins, viruses and cells, and chemical substances has increased in the fields of medicine, health, food, and drug discovery. Various biochips and microchemical chips (hereinafter collectively referred to as microchips) that can easily measure them have been proposed.

  The microchip can perform a series of experiments or analysis operations performed in the laboratory within a chip of several cm to 10 cm square and a thickness of several mm to several cm. There are many advantages such as low cost, high reaction rate, high throughput testing or analysis, and the ability to obtain test results immediately at the sample collection site.

  The microchip has a fluid circuit therein, and the fluid circuit mixes or reacts with a specimen (for example, blood or the like) to be tested or analyzed, or processes the specimen. A liquid reagent holding unit for holding the reagent; a measuring unit for measuring the sample and the liquid reagent; a mixing unit for mixing the sample and the liquid reagent; a detecting unit for performing inspection or analysis on the mixed solution And the like, and a connection flow path (thin flow path) that appropriately connects these parts. The microchip is typically used by being mounted on a device capable of applying a centrifugal force thereto. By applying a centrifugal force in the appropriate direction to the microchip, the sample (or a specific component in the sample) and / or liquid reagent can be weighed, the sample (or a specific component in the sample) mixed with the liquid reagent, and obtained. Processing such as introduction of the mixed liquid into the detection unit can be performed.

  For example, in Patent Document 1 (Japanese Patent Laid-Open No. 2006-76246) and Patent Document 2 (Japanese Patent Laid-Open No. 2006-310828), a flow path (fluid circuit) is formed by bonding a plurality of substrates by thermocompression bonding or light irradiation. There is disclosed a microchip on which is formed.

  In the conventional microchip manufacturing process in which a plurality of substrates are bonded together, for example, the first substrate 1 having a recess 10 for forming a fluid circuit as shown in FIG. The second substrate is bonded to each other and bonded together. However, due to the occurrence of sink marks (dents caused by molding shrinkage) during the molding of the first substrate, it is difficult to make the height of the partition walls forming the recesses 10 uniform. A low partition wall 11a and a partition wall 11b higher than other partition walls are formed. For this reason, the process margin of a bonding process is small, and it is difficult to bond the bonding surface of the 1st board | substrate 1 and the 2nd board | substrate 2 without excess and deficiency. That is, as shown in FIG. 17 (b), a poorly bonded portion 52 or a deformed portion 51 due to excessive welding is formed in part, resulting in insufficient separation between the fluid circuits 50, or a desired shape. In some cases, the fluid circuit 50 may not be formed.

JP 2006-76246 A JP 2006-310828 A

  The present invention obtains a microchip having a fluid circuit of a desired shape with a high yield rate without forming a defective bonding portion or a changed portion in manufacturing a microchip manufactured by bonding substrates. For the purpose.

The present invention comprises a first substrate having a recess defined by partition walls on at least one surface, and a second substrate bonded to at least one surface of the first substrate,
A microchip including a fluid circuit composed of the concave portion and the surface of the second substrate,
A microchip characterized in that at least a part of a tip of a partition partitioning the concave portion among the partition walls of the first substrate is welded to the second substrate through a weld rib. It is.

  It is preferable that a part of the welding rib has a liquid movement prevention stopper which is a part longer in the thickness direction of the partition than the other part.

In addition, the present invention provides a molding step of molding a first substrate having a recess defined by a partition wall on at least one surface;
A laminating step of laminating a second substrate on at least one surface of the first substrate;
By welding the tip of the partition of the first substrate to the second substrate, the first substrate and the second substrate are bonded together, and the recess and the surface of the second substrate A microchip manufacturing method comprising a bonding step of forming a fluid circuit composed of:
A welding rib is formed on a part of the tip of the partition that defines at least the concave portion of the partition of the first substrate,
In the bonding step, the partition wall defining the concave portion is welded to the second substrate through the welding rib.

  After the bonding step, it is preferable that the welding rib has a liquid movement prevention stopper which is a part longer in the thickness direction of the partition than the other part.

  Prior to the bonding step, it is preferable that the welding rib has an additional portion that is longer in the thickness direction of the partition wall than the other portion, or an additional portion that is longer in the height direction of the partition wall.

  Before the bonding step, a part of the partition of the first substrate may have a positioning step that is a convex portion that is higher than the other part of the partition and lower than the tip of the welding rib. preferable.

  In the microchip of the present invention, each substrate is welded via the welding rib, so that a fluid circuit having a desired shape is formed without forming a bonding failure portion or a changing portion. Moreover, a microchip having such a desired shape of the fluid circuit can be obtained with a high yield.

FIG. 3 is a schematic cross-sectional view showing the manufacturing process of the microchip of the first embodiment. (A) is the state before bonding of a board | substrate, (b) shows the state after bonding of a board | substrate. It is a top view which shows the 1st board | substrate before bonding used for the microchip of Embodiment 1. FIG. It is a schematic diagram which shows the cross section in the II surface of FIG. FIG. 10 is a schematic top view for explaining the effect of the microchip of the second embodiment. FIG. 5 is a schematic top view showing the microchip of the second embodiment. (A), (b) is a perspective view which shows an example of the shape of the welding rib used for Embodiment 2. FIG. It is a perspective view which shows an example of the shape of the welding rib used for Embodiment 2. FIG. It is a perspective view which shows an example of the shape of the welding rib used for Embodiment 2. FIG. It is a perspective view which shows an example of the shape of the welding rib used for Embodiment 2. FIG. It is a perspective view which shows an example of the shape of the welding rib used for Embodiment 2. FIG. It is a perspective view which shows an example of the shape of the welding rib used for Embodiment 2. FIG. It is a perspective view which shows an example of the shape of the welding rib used for Embodiment 2. FIG. It is a cross-sectional schematic diagram for demonstrating the effect of the microchip of Embodiment 3. FIG. (A) shows an example of the state after bonding of a board | substrate, (b) shows another example of the state after bonding of a board | substrate. FIG. 6 is a schematic cross-sectional view showing a microchip according to a third embodiment. (A) is the state before bonding of a board | substrate, (b) shows the state after bonding of a board | substrate. 6 is a top view illustrating an example of a microchip according to Embodiment 3. FIG. It is a schematic diagram which shows the cross section in the II-II surface of FIG. It is a cross-sectional schematic diagram which shows the manufacturing process of the conventional microchip. (A) is the state before bonding of a board | substrate, (b) shows the state after bonding of a board | substrate.

  The microchip of the present invention is a chip capable of performing various chemical synthesis, inspection, analysis, etc. using a fluid circuit included in the microchip, and has a first substrate having a recess partitioned by a partition wall on at least one surface. And a second substrate bonded to at least the one surface of the first substrate. The fluid circuit of the microchip includes a space constituted by the recess and the surface of the second substrate. The surface of the second substrate (the surface to be bonded to the first substrate) may be flat, or a recess corresponding to the recess of the first flat plate may be formed. The size of the microchip is not particularly limited, and can be, for example, about several cm to 10 cm in length and width and about several mm to several cm in thickness.

  Note that the microchip of the present invention may be composed of a substrate having three or more layers. For example, the first substrate further has a recess on the surface opposite to the second substrate. And the 3rd board | substrate similar to a 2nd board | substrate may be bonded by this recessed part side. In this case, the fluid circuit includes a first fluid circuit including a space formed by a recess provided on the second substrate side surface of the first substrate and the surface of the second substrate, and the first substrate. The second substrate has a two-layer structure composed of a second fluid circuit composed of a space formed by a recess provided on the third substrate side surface and the surface of the third substrate. Here, “two layers” means that fluid circuits are provided at two different positions in the thickness direction of the microchip. Such a two-layer fluid circuit can be connected by a through-hole penetrating the first substrate in the thickness direction.

  In the present invention, as a method for bonding the substrates together, a method (welding method) in which the bonding surfaces of at least one of the substrates to be bonded are melted and welded is used. As a welding method, a method of heating and welding a substrate; a method of irradiating light from a laser, a lamp, an LED, etc., and welding by heat generated during light absorption (laser welding, lamp welding, etc.); using ultrasonic waves And a method of welding (ultrasonic welding).

  Of the above-described substrates constituting the microchip of the present invention, the material of at least one of the substrates is a thermoplastic resin. It is more preferable that all the substrates are made of a thermoplastic resin, and it is more preferable that all the substrates are made of the same kind of thermoplastic resin. Examples of the thermoplastic resin include polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polybutylene terephthalate (PBT), polymethyl methacrylate (PMMA), polycarbonate (PC), polystyrene (PS), polypropylene (PP), Polyethylene (PE), polyarylate resin (PAR), acrylonitrile butadiene styrene resin (ABS), styrene-butadiene resin (styrene-butadiene copolymer), vinyl chloride resin (PVC), polymethylpentene resin (PMP), Examples include polybutadiene resin (PBD), biodegradable polymer (BP), cycloolefin polymer (COP), polydimethylsiloxane (PDMS), polyacetal (POM), and polyamide (PA).

  When the microchip is composed of a first substrate having a concave portion on the surface and a second substrate, the first substrate includes a portion irradiated with detection light in the optical measurement. A transparent substrate is preferable. The second substrate may be a transparent substrate or an opaque substrate. However, when laser welding is performed, it is preferable to use an opaque substrate because the light absorption rate can be increased, and a black substrate (for example, More preferably, the substrate is made of a resin containing a black pigment such as carbon black.

In the case where the microchip includes a first substrate having concave portions on both surfaces, a second substrate, and a third substrate, the first substrate is an opaque substrate from the viewpoint of laser welding efficiency. It is preferable to use a black substrate. On the other hand, the second and third substrates are preferably transparent substrates in order to construct the detection unit. When the second and third substrates are transparent substrates, a detection unit (optical measurement cuvette) can be formed from the through holes provided in the first substrate and the transparent second and third substrates, and the microchip. Optical measurement such as detecting the intensity (transmittance) of transmitted light by irradiating the detection unit with light from a direction substantially perpendicular to the surface can be performed.

  The method for forming the recesses (pattern grooves) and partition walls constituting the fluid circuit on the surface of the first substrate is not particularly limited, and injection molding using a mold having a transfer structure, imprinting, etc. Can be mentioned. The shapes of the recess and the partition are determined so as to obtain an appropriate fluid circuit structure.

  In the microchip of the present invention, the fluid circuit is suitable for the liquid in the fluid circuit (specimen, specific component in the specimen, liquid reagent, and a mixture or reaction liquid of two or more of these). It is equipped with various parts (reagent holding part, reagent measuring part, sample measuring part, mixing part, detecting part, etc.) arranged at appropriate positions in the fluid circuit so that fluid processing can be performed. The parts are appropriately connected via the connection flow path.

  Here, the “specimen” is a substance that is introduced into the fluid circuit and is a target for testing or analysis performed by the microchip, such as whole blood, plasma, serum, urine, and saliva. The “liquid reagent” is a reagent that processes a sample to be tested or analyzed by the microchip, or is mixed or reacted with the sample. Usually, the reagent of the fluid circuit is used in advance before using the microchip. Built in the holding part. The liquid mixture or reaction liquid finally obtained by mixing the sample and the liquid reagent, for example, irradiates the detection unit containing the liquid mixture with light and detects the intensity (transmittance) of the transmitted light. This method is used for optical measurement such as a method for measuring the absorption spectrum of the mixed liquid held in the detection unit, and inspection or analysis is performed.

Hereinafter, the present invention will be described in detail with reference to embodiments.
(Embodiment 1)
FIG. 1 is a schematic cross-sectional view illustrating a manufacturing process of the microchip of the first embodiment. (A) is the state before bonding of a board | substrate, (b) shows the state after bonding of a board | substrate. As shown in FIG. 1A, a recess 10 for forming a fluid circuit is provided on one surface of the first substrate 1, and a flat plate is formed on the recess 10 side of the first substrate 1. The second substrate is attached. Here, the partition wall 11 that partitions the recess 10 is formed with a partition wall 11a that is lower than the other partition walls 11 or a partition wall 11b that is higher than the other partition walls due to the occurrence of sink marks when the first substrate is formed. May end up. Even in this case, welding ribs 30 are formed on the bonding surfaces of the partition walls 11, 11a, and 11b, and the first substrate 1 and the second substrate 2 are welded ribs 31 as shown in FIG. Since the bonding process is performed through the sheet, the process margin of the bonding process is large, and the formation of the poor bonding part 52 and the deformed part 51 as shown in FIG. 17B is suppressed (FIG. 1B). ).

  FIG. 2 is a top view showing the first substrate 1 before bonding used in the microchip of the first embodiment. In the first substrate 1, the shape of the partition wall 11 is designed so that a desired recess 10 is formed, and the partition wall 11 is provided with a welding rib 30.

  The material of the welding rib is preferably at least the same as that of the first substrate in consideration of the molding process of the first substrate. However, the material of the welding rib may be a material different from that of the first substrate, for example, a material softer than the first substrate or a material having high adhesiveness.

  In FIG. 2, welding ribs 30 are provided on almost all partition walls 11, but of the partition walls 11 of the first substrate 1, at least the tips of the partition walls 11 (tips in the thickness direction of the first substrate 1). It is only necessary that the welding ribs 30 are provided in part, and the welding ribs 30 do not necessarily have to be provided at the tips of all the partition walls 11.

  FIG. 3 is a schematic diagram showing a cross section taken along the II plane of FIG. A welding rib 30 having a semicircular cross section is provided on the bonding surface 111 of the partition wall 11 of the first substrate.

(Embodiment 2)
In the present embodiment, a liquid movement prevention stopper is provided for preventing the liquid at a predetermined part in the fluid circuit from moving to another part. Other points are the same as in the first embodiment.

  When the first substrate and the second substrate are bonded via the welding rib as in the first embodiment, a remaining crushing gap 32 of the welding rib 31 may be formed (FIG. 1B). )), There is a case where the liquid that should stay in a predetermined part in the fluid circuit moves to another part through the gap 32 by the capillary phenomenon. That is, as shown in the schematic top view of FIG. 4, the remaining crushing gap 32 of the welding rib 31 may form a fine channel along the periphery of the welding rib. In some cases, the liquid 40 that should remain in a predetermined part moves to another part like the liquid 41 through the fine channel (gap 32). Such liquid movement hinders control of liquid movement in the fluid circuit, and accurate inspection cannot be performed.

  Therefore, in the present embodiment, as shown in FIG. 5, a liquid movement prevention stopper 301 for dividing the fine flow path (gap 32) and preventing the liquid 40 from moving to another part. Is provided. Specifically, the liquid movement prevention stopper is a part provided in a part of the welding rib and longer in the thickness direction of the partition wall than the other part. The material of the liquid movement preventing stopper is preferably the same as that of the welding rib in consideration of the molding process of the first substrate. However, the liquid movement preventing stopper may be made of a material different from the welding rib.

  6 to 12 are perspective views showing various examples of the shape of the welding rib used for forming the liquid movement preventing stopper in the second embodiment. Here, the shape of the welding rib in a state before the first substrate and the second substrate are bonded is shown.

  The added portion 300 of the welding rib shown in FIG. 6A has a cylindrical shape having a height of 0.15 mm which is the same as the height of the welding rib having a semicircular cross section having a radius of 0.15 mm. . The diameter of the cylinder circle is almost the same as the thickness (0.6 mm) of the partition wall 11. That is, the additional portion 300 is a portion that is longer in the thickness direction of the partition wall 11 than the other portions. 6B has a cylindrical shape having a height of 0.3 mm, which is higher than the height (0.15 mm) of the welding rib. The diameter of the cylinder circle is almost the same as the width (0.3 mm) of the welding rib 30. That is, the additional portion 300 is a portion that is longer in the height direction of the partition wall 11 than the other portions. Although not shown, the additional portion 300 of the welding rib may be a portion that is longer in the thickness direction of the partition wall 11 and longer in the height direction of the partition wall 11 than other portions.

  Such an additional portion 300 of the welding rib is crushed during the bonding step, and the liquid movement prevention stopper is provided on the bonding surface of the partition wall 11 of the first substrate, so that the first substrate and the first substrate Even when a fine flow path (gap) due to the remaining crushing of the welding rib 30 occurs when the substrate 2 is bonded, the fine flow path is divided, so that there is another liquid that should remain in the predetermined part. It can prevent moving to the part of.

  Considering that the additional portion 300 of the weld rib shown in FIG. 6 may prevent the weld rib 30 from being appropriately crushed during substrate bonding, as shown in FIG. The additional portion (portion longer in the thickness direction of the partition wall 11 than other portions) 300 may be conical. By setting it as such a shape, it is thought that the welding rib 30 and the additional part 300 become easy to be crushed to the same extent at the time of bonding of a board | substrate.

  The additional portions 300 of the welding ribs (portions longer in the thickness direction of the partition wall 11 than other portions) 300 shown in FIG. 8 have the same shape as the welding ribs 30 and are provided on both sides of the welding ribs. Depending on the design of the fluid circuit, it is not always necessary to provide such additional portions 300 on both sides of the welding rib 30, and the additional portions 300 may be provided only on one side as shown in FIG. 9. Further, in order to enhance the liquid movement prevention effect, a plurality of additional portions 300 may be provided as shown in FIG.

  Also in the case where the additional portion 300 having the shape as shown in FIGS. 8 to 10 is provided, it is shown in FIG. 11 in consideration of the possibility that the welding rib 30 may be appropriately crushed when the substrates are bonded. As described above, a cutout portion 300 a may be provided in a part of the additional portion 300. By setting it as such a shape, it is thought that the welding rib 30 and the additional part 300 become easy to be crushed to the same extent at the time of bonding of a board | substrate.

  Further, as shown in FIG. 12, an additional portion 300 (a portion longer in the thickness direction of the partition wall 11 than other portions) 300 having the same shape as the weld rib may be provided in an oblique direction with respect to the partition wall 11. By arranging the additional portion 300 in this manner, it is considered that the effect of stopping the movement of the liquid is enhanced. Note that a part of the liquid movement prevention stopper shown in FIG. 12 can be omitted depending on the design of the fluid circuit.

(Embodiment 3)
In this embodiment, before the bonding step, a part of the partition of the first substrate is provided with a positioning step that is a convex part higher than the other part of the partition and lower than the tip of the welding rib. Yes. Other points are the same as in the first embodiment.

  Even when the first substrate and the second substrate are bonded via the welding rib as in the first embodiment, the positional relationship between the two in the step of bonding the first substrate and the second substrate. In such a case, the deformed portion 51 due to excessive welding as shown in FIG. 13 (a) is formed, or as shown in FIG. 13 (b), a poorly bonded portion that is not completely bonded. 52 and the poor bonding part 53 in which bonding was insufficient were formed, and there was a possibility that the separation between the fluid circuits 50 would be insufficient.

  Therefore, in this embodiment, as shown in FIG. 14A, a positioning step 12 is provided. This positioning step 12 is a convex part in a part of the partition wall 11 of the first substrate 1 higher than the other part of the partition wall 11 and lower than the tip of the welding rib 30 before the bonding step. By providing the positioning step 12, as shown in FIG. 14 (b), the distance between the first substrate 1 and the second substrate 2 after the bonding step is appropriately maintained. The formation of the defective portions 52 and 53 (see FIGS. 13A and 13B) can be suppressed. In FIG. 14A, the positioning step 12 is provided in the partition wall 11 at the end, but the positioning step 12 may be provided in another partition wall 11.

  FIG. 15 is a top view showing the first substrate 1 before bonding used in the microchip of the third embodiment. The first substrate 1 is the same as the first substrate 1 shown in FIG. 2 except that a positioning step 12 is provided.

  16 is a schematic diagram showing a cross section taken along the plane II-II in FIG. A positioning step 12 is provided on the bonding surface side of the partition wall 11 of the first substrate. The thickness a of the partition wall 11 in FIG. 16 and the thickness c of the partition wall 11 in FIG. 3 are usually different. If the height of the positioning step in FIG. 16 is b, the sectional area of the weld rib (for example, The area of the semicircle in the cross section of the welding rib 30 in FIG. 3 is preferably substantially equal to c × b. This is because by setting the height b of the positioning step 12 to such a height, after the bonding step, the welding rib spreads over and over in the thickness direction of the partition wall on the bonding surface and becomes an appropriate shape. .

  However, even in this case, the height of the partition walls forming the recess 10 may not be uniform due to the occurrence of sink marks or the like when the first substrate is formed, and the first substrate and the second substrate May be formed through the welding ribs to form a remaining crushing gap 32 of the welding ribs 31 (see FIG. 14B). Therefore, in order to prevent the liquid at a predetermined site in the fluid circuit from moving to another site due to capillary action, it is preferable to provide a liquid movement prevention stopper as described in the second embodiment.

  The embodiment disclosed this time should be considered as illustrative in all points and not restrictive. The scope of the present invention is defined by the terms of the claims, rather than the description above, and is intended to include any modifications within the scope and meaning equivalent to the terms of the claims.

  DESCRIPTION OF SYMBOLS 1 1st board | substrate, 10 recessed part, 11, 11a, 11b partition, 111 bonding surface, 12 positioning step, 2nd board | substrate, 30, 31 welding rib, 300 addition part, 300a notch part, 301 liquid movement prevention stopper , 32 gap, 40, 41 liquid, 50 fluid circuit, 51 deformed part, 52, 53 poor bonding part.

Claims (10)

A first substrate having a recess defined by a partition wall on at least one surface, and a second substrate bonded to at least one surface of the first substrate;
A microchip including a fluid circuit composed of the concave portion and the surface of the second substrate,
A welding rib in which at least a part of a tip of the partition partitioning the concave portion of the first substrate is separated from an end of the partition and is formed along the flow path of the fluid circuit. A microchip, which is welded to the second substrate via a substrate. The microchip according to claim 1, further comprising a liquid movement prevention stopper formed on the partition wall so as to extend from the welding rib to an end portion of the partition wall. The microchip according to claim 2, wherein the liquid movement prevention stopper is formed to extend from the welding rib to both end portions of the partition wall.   2. The microchip according to claim 1, wherein a part of the welding rib has a liquid movement prevention stopper that is a part longer in the thickness direction of the partition than the other part. A molding step of molding a first substrate having a recess defined by a partition wall on at least one surface;
A laminating step of laminating a second substrate on at least one surface of the first substrate;
By welding the tip of the partition of the first substrate to the second substrate, the first substrate and the second substrate are bonded together, and the recess and the surface of the second substrate A microchip manufacturing method comprising a bonding step of forming a fluid circuit composed of:
Among the partition walls of the first substrate, welding ribs formed at least at a part of the front end of the partition walls defining the recesses and spaced from the end portions of the partition walls and along the flow path of the fluid circuit. Formed,
In the bonding step, the partition wall defining the recess is welded to the second substrate via the welding rib. The method for manufacturing a microchip according to claim 5, further comprising a liquid movement prevention stopper formed on the partition wall so as to extend from the welding rib to an end portion of the partition wall. The microchip according to claim 6, wherein the liquid movement prevention stopper is formed to extend from the welding rib to both end portions of the partition wall. 6. The method of manufacturing a microchip according to claim 5 , wherein after the bonding step, the welding rib has a liquid movement prevention stopper which is a part longer in the thickness direction of the partition wall than the other part in the part. . In front of the bonding step, the weld rib is longer appendixes in the thickness direction of the partition wall than other portions in a part or, has a long additional part in a height direction of the partition wall, claim 5 The manufacturing method of the microchip of any one of -8 . Before the bonding step, a part of the partition of the first substrate has a positioning step that is a convex portion that is higher than the other part of the partition and lower than the tip of the welding rib. microchip fabrication method according to any one of clauses 5-9.

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