JP2016038272A - Microchip and manufacturing method thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a microchip in which a plurality of substrates are stuck together by fusion via a fusion rib and a minute fluid circuit portion is possessed, yet entry of the fusion rib to that portion and the consequential change of shape or blocking of the portion are effectively suppressed, and a method for manufacturing the microchip.SOLUTION: The present invention provides a microchip and a manufacturing method therefor, the microchip including: a first substrate having a recess delimited by a barrier on at least one surface; a second substrate stuck to the surface; and a fluid circuit configured from the recess and the surface on first substrate side of the second substrate. The first and the second substrates are stuck together by fusion via a fusion rib provided on the second substrate side surface in at least part of the barrier. The recess includes a minute recess of 0.2 mm or less in width and/or 0.2 mm or less in depth, the width of a fusion rib provided in the barrier delimiting the minute recess being 0.5 mm or less in a state in which the first and the second substrates are stuck together by fusion.SELECTED DRAWING: Figure 3

Description

  The present invention relates to a microchip that can be suitably used for biochemical tests (blood tests, etc.), chemical synthesis or analysis.

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

  Microchips can perform a series of inspection and analysis operations that have been conventionally performed in laboratories in a small chip, so that only a small amount of sample and liquid reagent are required, the cost is low, the reaction rate is high, and high-throughput inspection and analysis are possible. It has many advantages such as being able to analyze and obtaining test / analysis results immediately at the site where the sample is collected.

  The microchip is referred to as a “fluid circuit (or microfluidic circuit)”, a plurality of types of sites (chambers) for performing specific processing on liquids such as specimens and liquid reagents existing in the circuit, 2. Description of the Related Art Conventionally, what has a flow path network constituted by flow paths connecting these parts therein is known.

  A microchip having a fluid circuit therein can be manufactured by forming a substrate having concave portions of a predetermined pattern forming a fluid circuit on the surface and bonding another substrate to the surface having the concave portions by welding. In Patent Document 1, as a means for suppressing poor bonding between substrates and deformation of recesses due to sink marks (dents caused by molding shrinkage) that occur when a substrate having recesses is molded, partition walls that partition the recesses It is described that a welding rib serving as a portion to be welded at the time of substrate welding and bonding is separately provided on the surface (bonding surface with the other substrate), and the substrate is bonded and bonded through the welding rib. Has been.

JP 2012-237707 A

  An object of the present invention is a microchip in which a plurality of substrates are welded and bonded through the above-described welding ribs, and the welding is performed on the microchip even though it has a fine fluid circuit portion. An object of the present invention is to provide a microchip in which the intrusion of ribs and the accompanying shape change and blockage of the portion are effectively suppressed, and a method for manufacturing the microchip.

The present invention provides the following microchip and manufacturing method thereof.
[1] A first substrate having a recess defined by a partition wall on at least one surface;
A second substrate bonded onto the surface of the first substrate;
A fluid circuit comprising a space constituted by the first substrate side surface of the recess and the second substrate;
Including
The first substrate and the second substrate are welded and bonded via the welding rib provided on the second substrate side surface in at least a part of the partition wall,
The recess includes a fine recess having a width of 0.2 mm or less and / or a depth of 0.2 mm or less, and the width of the welding rib provided on the partition wall defining the fine recess is The microchip which is 0.5 mm or less in a state where the first substrate and the second substrate are bonded to each other.

[2] A microchip that moves liquid existing in a fluid circuit by applying centrifugal force in the fluid circuit,
The fluid circuit includes at least one part selected from the group consisting of a part for limiting the flow rate of the liquid, a part for measuring the liquid, and a part for separating the liquid into components.
The microchip according to [2], wherein the at least one portion is configured by the fine concave portion.

  [3] The microchip according to [2], wherein the liquid is blood or a component thereof and is used for blood tests.

[4] A step of forming a first substrate having a concave portion partitioned by a partition wall on at least one surface and having a welding rib on the second substrate side surface in at least a part of the partition wall using a mold;
A step of welding and bonding the first substrate and the second substrate through the welding rib;
Including
The manufacturing method in which at least a part of the welding ribs is formed as a transfer structure of the surface shape of the mold member in a portion along a parting line of at least two mold members used in combination.

  [5] The production method according to [4], wherein the maximum width of the at least some welding ribs is less than 0.3 mm (preferably less than 0.2 mm) before the welding and bonding step.

  [6] The manufacturing method according to [4] or [5], wherein an angle of a tip of the at least some welding ribs is 10 to 90 °.

  According to the present invention, a microchip having an extremely fine fluid circuit portion can be provided. Moreover, although it has a fine fluid circuit part, the penetration | invasion of the welding rib there, and the shape change and obstruction | occlusion of the said part accompanying this can be suppressed effectively.

It is a top view which shows an example of the 1st board | substrate which comprises a microchip. It is a cross-sectional schematic diagram which shows a mode that a 1st board | substrate and a 2nd board | substrate are welded together through the welding rib which a 1st board | substrate has, FIG. 2 (a) is the state before welding bonding, FIG. ) Shows the state after welding and bonding. It is a cross-sectional schematic diagram which expands and shows another example of the fine recessed part which a 1st board | substrate has, the partition which divides this, and those vicinity. It is the photograph which expands partially the 1st board | substrate with which the fine recessed part actually produced using the metal mold | die, and the partition which partitions this, and the partition which has a welding rib on the surface was provided. FIG. 5 is a photograph showing a partially enlarged microchip actually fabricated by using the first substrate shown in FIG. 4 and bonding the second substrate thereto by ultrasonic welding. It is a cross-sectional schematic diagram which shows another example of the 1st board | substrate which comprises a microchip. It is a cross-sectional schematic diagram which shows the method of producing the 1st board | substrate using a metal mold | die.

<Outline of microchip>
The microchip of the present invention is a chip that performs a biochemical test (blood test, etc.), chemical synthesis or analysis (environmental analysis, etc.) using a fluid circuit (a space formed inside). , Liquid in the fluid circuit (specimen, components in the specimen, reagent such as liquid reagent, and a mixture of two or more of these) by applying centrifugal force to a predetermined part (chamber) in the fluid circuit By sequentially moving the liquid, the liquid can be subjected to appropriate processing (hereinafter, various types of processing performed on the liquid in the fluid circuit are collectively referred to as “fluid processing”). . For this purpose, the fluid circuit includes various parts (chambers) arranged at appropriate positions, and these parts are appropriately connected via a flow path. In the inspection or analysis, the fluid processing is typically a pretreatment for inspection or analysis.

  The “specimen” refers to a sample to be tested or analyzed introduced into the fluid circuit or a component extracted from the sample, and both are typically liquid. A “liquid reagent” is a reagent for mixing or reacting with a specimen or processing the specimen. The liquid reagent is usually built in the liquid reagent holding part of the fluid circuit in advance before the inspection / analysis of the specimen using the microchip.

  The part (chamber) of the fluid circuit includes a liquid reagent holding unit for containing a liquid reagent; a separation unit for taking out specific components from the sample introduced into the fluid circuit (component separation); (Including the case where it is a constituent component in the sample as described above; the same applies hereinafter); a liquid reagent measuring unit for measuring the liquid reagent; and mixing the sample and the liquid reagent Mixing unit for (or reacting); Detection unit for performing inspection or analysis of the obtained mixed liquid (for example, detection or quantification of specific components in the mixed liquid); Limiting the flow rate of the moving liquid, etc. For example, there may be mentioned a flow restricting unit; a storing unit for temporarily storing a specific liquid; a waste liquid storing unit for storing an unnecessary liquid.

  The flow rate restricting unit refers to the liquid flow rate and / or the liquid just before being introduced into these parts in order to allow the liquid to be smoothly introduced into the measuring unit, the separating unit, and the like without air entrainment. This is a portion including a channel portion having a narrow channel width (or a small channel cross-sectional area) provided to reduce the width.

  The microchip usually has a reagent injection port, which is a through-hole penetrating to the liquid reagent holding unit, for injecting the liquid reagent into the liquid reagent holding unit on one surface thereof. The reagent inlet is sealed by adhering a sealing layer (for example, a plastic film having a pressure-sensitive adhesive layer on one side, a label, a seal, etc.) to the microchip surface after the liquid reagent is injected. . Further, the microchip has on its surface a specimen injection port (including a sample tube mounting portion described later) for injecting a specimen that is a through-hole penetrating to the fluid circuit (connected to the fluid circuit).

  A method for performing inspection or analysis on the mixed liquid introduced into the detection unit is not particularly limited. For example, the intensity (transmittance) of light transmitted through the detection unit containing the mixed liquid is irradiated with light. ) And a method of measuring an absorption spectrum of the mixed liquid held in the detection unit.

  The microchip may have all of the above-described exemplified portions (chambers) or may not have any one or more. Moreover, you may have site | parts other than these illustrated site | parts. There is no restriction | limiting in particular also about the number of each site | part, It can be 1 or 2 or more.

  Extraction of specific components from the sample (component separation), discharge of the liquid reagent from the liquid reagent holding unit, measurement of the sample and the liquid reagent, mixing of the sample and the liquid reagent (that is, at the site for mixing them) Various fluid treatments in the fluid circuit, such as movement to a certain mixing unit), introduction of the obtained mixture into the detection unit, and other movement from one site to another, are appropriate for the microchip. This can be performed by sequentially applying a centrifugal force in any direction and sequentially moving the target liquid to a predetermined site arranged at a predetermined position. For example, the measurement of the sample and the liquid reagent by the measurement unit is performed by applying the centrifugal force of the sample or liquid reagent to be measured to the sample measurement unit or the liquid reagent measurement unit having a predetermined volume (the same amount as the amount to be measured). It can be carried out by introducing by applying and overflowing an excessive amount of the sample or liquid reagent from the sample measuring unit or the liquid reagent measuring unit. The overflowed sample or liquid reagent can be stored in a waste liquid storage unit or the like connected to the sample measurement unit or the liquid reagent measurement unit via the flow path.

  Application of centrifugal force to the microchip can be performed by placing the microchip on a device (centrifuge) to which centrifugal force can be applied. The centrifuge device includes a first stage rotatable around a first axis and a second stage disposed on the first stage and rotatable around a second axis on the first stage. Can do. By placing the microchip on the second stage, rotating the second stage to arbitrarily set the angle of the microchip with respect to the first stage, and rotating the first stage, the microchip can be arbitrarily set. Directional centrifugal force can be applied.

  The microchip can be configured to include a first substrate and a second substrate that is welded and bonded onto the first substrate. For example, the microchip includes a first substrate and a second substrate that is welded and bonded onto the first substrate. (Hereinafter, such a microchip composed of two substrates is also referred to as “form A”). In this case, a recess having a predetermined pattern for forming a fluid circuit is provided on the surface of the first substrate (the surface on the side facing the second substrate). A recessed part can be provided by forming the partition which divides this in the said surface. A fluid circuit as an internal space is constructed by welding and laminating both substrates with the concave portion inside. A recess for forming a fluid circuit may be further provided on the surface of the second substrate (the surface on the side facing the first substrate). The shape of the recess and the partition wall partitioning the recess is determined so that the structure of the internal space is a desired fluid circuit structure.

  The microchip of form A is described in, for example, Japanese Patent Application Laid-Open No. 2009-258013. The fluid circuit structure itself of the microchip of the present invention is not particularly limited, but can be a structure as disclosed in this document, for example.

  The microchip may be formed by laminating the second substrate, the first substrate, and the third substrate in this order, and bonding them together (hereinafter, the microchip composed of three substrates is referred to as “form” B "). In this case, recesses for forming a fluid circuit are provided on both surfaces of the first substrate disposed between the second substrate and the third substrate, and the microchip is constructed by the first substrate and the second substrate. A two-layer fluid circuit including one fluid circuit and a second fluid circuit constructed by the first substrate and the third substrate is provided. “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 one or more through holes penetrating the first substrate in the thickness direction. A recess for forming a fluid circuit may be further provided on the surface of the second substrate and the third substrate (surface on the side facing the first substrate).

  The microchip of form B is described in, for example, Japanese Patent Application Laid-Open No. 2009-133805. The fluid circuit structure itself of the microchip of the present invention is not particularly limited, but may be a structure as disclosed in this document, for example. A microchip can also be configured using four or more substrates.

  The substrates are bonded together by a welding method. Examples of the welding method include a method of welding by heating the substrate; a method of irradiating light such as a laser and welding by heat generated by light absorption (laser welding); a method of welding using ultrasonic waves, and the like. Among them, ultrasonic welding is preferable. In any of the methods, it is a welding rib provided on the first substrate that melts at the time of substrate welding and bonds and plays the role of substrate adhesion.

  The size of the microchip is not particularly limited, and can be, for example, about several cm to ten cm in length and width and about several mm to several cm in thickness.

  The material of each substrate constituting the microchip of the present invention is not particularly limited. For example, polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polymethyl methacrylate (PMMA), polycarbonate (PC), polystyrene (PS) , Polypropylene (PP), polyethylene (PE), polyethylene naphthalate (PEN), polyarylate resin (PAR), acrylonitrile / butadiene / styrene resin (ABS), vinyl chloride resin (PVC), polymethylpentene resin (PMP), Thermoplastic resins such as polybutadiene resin (PBD), biodegradable polymer (BP), cycloolefin polymer (COP), and polydimethylsiloxane (PDMS) can be used.

  In the microchip of the form A, it is preferable that at least one of the substrates is a transparent substrate in order to construct a detection unit for optical measurement using detection light. The other 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. More preferably, a black substrate is formed by adding a black pigment such as carbon black into the thermoplastic resin.

  In the microchip of form B, from the viewpoint of laser welding efficiency, the first substrate disposed between the second substrate and the third substrate is preferably an opaque substrate, and more preferably a black substrate. preferable. On the other hand, the second and third substrates are preferably transparent substrates for the same reason as described above.

<Specific configuration of microchip>
As described above, the microchip of the present invention is formed by welding and bonding a first substrate having concave portions partitioned by partition walls on at least one surface and a second substrate bonded on the surface of the first substrate. It will be. Thereby, the fluid circuit which consists of the space comprised from the recessed part and the 1st board | substrate side surface in a 2nd board | substrate is formed inside. In the first substrate, the second substrate side surface of at least a part of the partition wall is formed with a welding rib for performing welding between the substrates, and the first substrate and the second substrate are bonded to each other via the welding rib. Combined.

  FIG. 1 is a top view showing an example of a first substrate 100 constituting a microchip, and shows a surface on the second substrate side of the first substrate 100. A microchip is manufactured by welding and bonding a second substrate (not shown) having the same outer shape to this surface. The hatched area in the figure is the second substrate side surface of the partition wall 11 defining the recess, and a welding rib (not shown) is provided on this surface. The part other than the hatched area is basically a recess. The welding rib can be provided on all or almost all of the partition walls 11, but may be provided on at least a part of the partition walls 11 as long as sufficient adhesion between the substrates can be ensured. The width of the welding rib is usually smaller than the width of the surface portion on the second substrate side of the partition wall 11 on which the welding rib is provided. The details and usage of the microchip fluid circuit using the first substrate 100 shown in FIG. 1 will be described later.

  FIG. 2 is a schematic cross-sectional view showing a state in which the first substrate 100 and the second substrate 200 are welded and bonded through the welding ribs of the first substrate 100, and FIG. 2 (a) is before the welding and bonding. FIG. 2B shows the state after welding and bonding. As shown in FIG. 2 (a), a recess 10 for forming a fluid circuit and a minute recess 10a, which is a particularly minute recess, are provided on one surface of the first substrate 100. For example, a flat plate-like second substrate 200 is bonded to the concave portion side of the substrate 100. Welding ribs 30, 30a, 30b are provided on the second substrate 200 side surface of the partition walls 11, 11a, 11b partitioning the concave portion 10 and the fine concave portion 10a, and the substrates are bonded by melting them. With reference to FIG.2 (b), the 1st board | substrate 100 and the 2nd board | substrate 200 are laminated | stacked via the welding rib 40, 40a, 40b (after bonding) in the produced microchip. . FIG. 3 is an enlarged schematic cross-sectional view showing another example of the fine recess 10a of the first substrate 100, partition walls 11a and 11b partitioning the fine recess 10a, and the vicinity thereof.

  According to the present invention, since the welding rib can be formed with a very narrow width on the surface of the partition wall defining the concave portion, the amount of the welding rib that melts at the time of substrate welding bonding can be reduced, and the melted out. It can suppress or prevent effectively that a welding rib penetrate | invades into the adjacent recessed part. As a result, it is possible to provide the fine concave portion 10a, which is a particularly fine concave portion, as at least a part of the fluid circuit, and a welding rib enters the provided fine concave portion 10a. It can suppress or prevent that a cross-sectional shape changes or the fine recessed part 10a is obstruct | occluded.

  Here, the fine recess 10a refers to a recess having a width of 0.4 mm or less and / or a depth of 0.5 mm or less. The width of the fine recess may be 0.3 mm or less, further 0.2 mm or less, and the depth may be 0.3 mm or less, further 0.2 mm or less. The width and depth of the fine recess 10a are usually 0.05 mm or more. The width of the recesses 10 other than the fine recesses 10a is greater than 0.4 mm and the depth is greater than 0.5 mm.

  Examples of the part (chamber) in the fluid circuit that is desirably constructed by the fine recess 10a include a part where the flow path width should be narrowed and a part where the capacity (volume) should be set precisely. A specific example of the former is a flow rate limiting unit for reducing the flow rate and / or width of a liquid, and a specific example of the latter is a measuring unit for measuring a liquid (a sample measuring unit for measuring a sample and A liquid reagent measuring unit for measuring a liquid reagent) and a separating unit for separating the components of the specimen. In the microchip of the present invention, it is preferable that at least one of these parts is composed of the fine recesses 10a, and it is more preferable that all the parts are composed of the fine recesses 10a.

  Referring to FIG. 3, welding ribs 30a and 30b provided on the second substrate side surface of partition walls 11a and 11b that define fine recess 10a are formed with a very narrow width. (Before substrate welding and bonding) is preferably at most less than 0.3 mm, more preferably at most 0.2 mm or less, still more preferably at most 0.1 mm or less. Thereby, the quantity of welding rib 30a, 30b which melts | dissolves at the time of board | substrate welding bonding can be reduced effectively. The width W (before substrate welding bonding) is usually 0.02 mm or more in the maximum width. The width of the welding ribs 40a and 40b after the substrate welding and bonding (that is, in the microchip) is at most 0.5 mm, preferably at most 0.3 mm, and usually at the maximum width of 0.05 mm. That's it.

  The width of the welding rib 30 provided on the second substrate side surface of the partition wall 11 that defines the recesses 10 other than the fine recesses 10a (before the substrate welding bonding) may not be as narrow as the welding ribs 30a and 30b. It is good also as a width | variety comparable as rib 30a, 30b.

  The welding ribs 30a and 30b are preferably relatively high (the same applies to the welding rib 30). As shown in FIG. 2A, the height of the plurality of partition walls may not be uniform due to the occurrence of sink marks or the like when the first substrate 100 is formed. By making the welding ribs 30, 30a, 30b high, bonding defects (a phenomenon in which the contact area between the partition walls and the second substrate is insufficient or not in contact) occur in a part of the partition walls, or melted welding ribs. Can be suppressed or prevented from entering into the recesses or causing deformation of the recesses due to excessive welding (a phenomenon in which not only the welding ribs but also the partition walls are melted and the recesses are crushed when the substrates are bonded together). Referring to FIG. 3, the height H of the welding ribs 30a and 30b is preferably 0.1 mm or more, and more preferably 0.15 mm or more (the same applies to the welding rib 30). The height H is usually 0.5 mm or less (the same applies to the welding rib 30).

  The shape of the welding ribs 30, 30a, 30b is not particularly limited. For example, the welding ribs 30, 30a, 30b can have a triangular cross-sectional shape as shown in FIGS. May have a cross-sectional shape. The welding ribs 30, 30a, 30b preferably have a tapered shape such as a triangular cross section. Such a tapered shape is advantageous in that the bonding ribs can be easily melted and the bonding can be efficiently performed, particularly when the substrates are bonded by ultrasonic welding. For the same reason, the welding ribs 30, 30a, 30b are tapered, and the tip angle is more preferably 10 to 90 °, and further preferably 30 to 45 °.

  The welding ribs 30, 30a, 30b are formed on the second substrate side surface of the partition walls 11, 11a, 11b, and are continuous along the direction in which the second substrate side surface of the partition walls 11, 11a, 11b extends. Can be formed. However, as described above, the welding ribs 30, 30a, 30b may be provided on at least a part of the partition walls 11, 11a, 11b as long as sufficient adhesion between the substrates can be ensured.

  The material of the welding ribs 30, 30 a, 30 b is preferably at least the same as that of other parts of the first substrate 100 in consideration of the molding process of the first substrate 100. However, a material different from that of the first substrate 100 may be used. For example, a material softer than the first substrate 100 or a material having high adhesiveness may be used.

  A black first substrate (made of a thermoplastic resin) having a fine recess 10a actually manufactured using a mold and partition walls partitioning the micro recess 10a and having partition walls having welding ribs 30a and 30b on the surface thereof. A partially enlarged photograph is shown in FIG. Further, a part of the microchip actually produced by using the first substrate shown in FIG. 4 and bonding a transparent second substrate (made of thermoplastic resin) by ultrasonic welding to the fine recess forming surface side. An enlarged photograph is shown in FIG. In the first substrate shown in FIG. 4, the width of the flow path formed of the fine recesses 10a is 0.1 mm, and the depth is 0.1 mm. The width of the welding ribs 30a and 30b is 0.15 mm, and the height is 0.15 mm. The cross-sectional shape of the welding ribs 30a and 30b was a tapered triangle, and the tip angle was 45 °. The width of the surface on the second substrate side of the partition wall on which the welding ribs 30a and 30b are formed was 0.3 mm.

  The conditions for ultrasonic welding were welding energy 120J (welding mode: welding energy control), bonding force: 500 N, temperature: room temperature (25 ° C.).

  As is apparent from the photograph of FIG. 5 showing the microchip produced by the substrate welding and bonding, there is no penetration of the welding rib into the fine recess 10a, and the fine recess 10a maintains its shape before and after the substrate welding and bonding. doing. Further, no defect is observed in the adhesion between the welding rib and the second substrate. The width | variety of the welding rib 40a, 40b after board | substrate welding bonding was 0.3 mm.

  FIG. 6 is a schematic cross-sectional view showing another example of the first substrate constituting the microchip. For example, it can be said that the first substrate 100 shown in FIG. 2A has a structure in which partition walls 11, 11a, and 11b are attached to a flat substrate portion, but the present invention is not limited to this, and the first substrate 100 shown in FIG. Like the substrate 101, the first substrate may have a structure in which a concave portion is carved into a flat substrate. In the case of a structure in which a partition is attached to a flat substrate portion, there are necessarily recesses on both sides of the welding rib. On the other hand, in the case of a structure in which a recess is carved in a flat substrate, the recess may not exist on one side. In such a case, as shown in FIG. 6, an additional recess 50 may be formed on the one side. This additional recess 50 is a pocket for receiving the welding rib that has melted during the substrate welding and bonding and flows out beyond the partition wall surface. By providing the additional recess 50, In the event of the above, it is possible to more effectively suppress the penetration of the welded rib that has melted into the concave portion constituting the fluid circuit.

  Next, details of a microchip fluid circuit using the first substrate 100 shown in FIG. 1 and a method of using the same will be described. This microchip can be suitably used for blood tests, and its fluid circuit includes a sample tube mounting unit 151 for mounting (loading) a sample tube from which a sample is collected; A flow rate limiting unit 152 for limiting the liquid width; a separation unit 153 for separating the components of the sample; a liquid reagent holding unit 154, 155 for storing the liquid reagent; a sample measuring unit for measuring the components in the sample 156; Liquid reagent measuring units 157 and 158 for measuring liquid reagents; Mixing units 159, 160, 161 and 162 for mixing liquids or promoting mixing; Examination or analysis of the obtained mixed liquid Detection unit 163 for performing; including waste liquid storage units 164 and 165 for storing waste liquid. Each of the liquid reagent holding units 154 and 155 has reagent injection ports 166 and 167 penetrating the first substrate 100 in the thickness direction for injecting the liquid reagent therein.

  Among the above-mentioned various parts, it is preferable that at least one selected from the flow restriction unit 152, the separation unit 153, the sample measurement unit 156, and the liquid reagent measurement units 157 and 158 is composed of the fine recesses 10a, and all the parts are fine. More preferably, the recess 10a is configured.

  The sample testing / analysis method using this microchip is simple, taking as an example the case where the sample is whole blood, the plasma component is extracted from the whole blood in the fluid circuit, and this plasma component is tested / analyzed. The explanation is as follows. First, a sample tube from which whole blood is collected is loaded into the sample tube mounting unit 151. Next, a centrifugal force is applied to the microchip in the leftward direction in FIG. 1 (hereinafter referred to simply as “leftward”; the same applies to the other directions hereinafter), and whole blood is taken out from the sample tube, and then centrifuged downward. Whole blood is introduced by force into the separation unit 153 via the flow rate restriction unit 152 and centrifuged to separate the plasma component and the blood cell component. When whole blood is introduced into the separation unit 153, the whole blood overflowing from the whole blood is stored in the waste liquid storage unit 164. Further, by this downward centrifugal force, the liquid reagent S1 in the liquid reagent holding unit 154 is introduced into the liquid reagent measuring unit 157 and measured. When the liquid reagent S1 is introduced into the liquid reagent measuring section 157, the liquid reagent S1 overflowing from the liquid reagent measuring section 157 is stored in the overflow liquid storage section 164.

  Next, the separated plasma component is introduced into the sample measuring unit 156 by a rightward centrifugal force and measured. When the plasma component is introduced into the sample measuring unit 156, the plasma component overflowing from the sample component is stored in the waste liquid storage unit 165. Further, by this rightward centrifugal force, the liquid reagent S1 measured by the liquid reagent measuring unit 157 moves to the mixing unit 160, and the liquid reagent S2 in the liquid reagent holding unit 155 is discharged from the discharge port.

  Next, the measured plasma component and the liquid reagent S1 are mixed in the mixing unit 159 by downward centrifugal force. Further, the liquid reagent S2 is measured by the liquid reagent measuring unit 158 by the downward centrifugal force. Next, rightward, downward, and rightward centrifugal forces are sequentially applied, and the mixed solution is moved back and forth between the mixing units 159 and 160 to sufficiently mix the mixed solution.

  Next, the mixed liquid composed of the liquid reagent S1 and the plasma component and the measured liquid reagent S2 are mixed in the mixing unit 161 by upward centrifugal force. Next, leftward, upward, leftward, and upward centrifugal forces are sequentially applied, and the mixed solution is moved back and forth between the mixing units 161 and 162 to sufficiently mix the mixed solution. Finally, the mixed liquid in the mixing unit 161 is introduced into the detection unit 163 by a rightward centrifugal force. The liquid mixture in the detection unit 163 is subjected to optical measurement such as irradiating the detection unit 163 with light and measuring the intensity of the transmitted light.

<Microchip manufacturing method>
The above-described microchip according to the present invention includes the following steps:
Forming a first substrate having a concave portion partitioned by a partition wall on at least one surface and having a welding rib on the second substrate side surface in at least a part of the partition wall; and via the welding rib And it can manufacture suitably by the method including the process of welding and bonding a 1st board | substrate and a 2nd board | substrate. Note that this manufacturing method uses a first substrate having a recess having a relatively large width and depth, for example, a width exceeding 0.2 mm and / or a depth exceeding 0.2 mm. It can also be suitably used in a method of manufacturing a microchip, and thereby the quality of the microchip, the accuracy of the fluid circuit, the yield, and the like can be improved.

  As described above, in the present invention, it is necessary to form the welding rib provided on the second substrate side surface of the partition wall defining the fine concave portion with a very narrow width. It is difficult to cut and carve a narrow recess corresponding to the welding rib. Therefore, referring to FIG. 7, when forming narrow welding ribs 30a on the partition walls of the first substrate 100, mold parting lines (partition lines) are used.

  That is, for example, a core mold is composed of at least two mold members (a first mold member 301 and a second mold member 302 in FIG. 7) used in combination, and a portion along the parting line. The surfaces of the mold members 301 and 302 are processed so that the surface shapes of the mold members 301 and 302 in FIG. 3 become a transfer structure of the shape of the narrow welding rib 30a when these mold members are combined. Thus, the first substrate 100 having the narrow welding rib 30a can be formed. Since the surface processing of the mold members 301 and 302 corresponding to the narrow welding rib 30a corresponds to the processing of the end of the mold member, a desired shape is obtained regardless of the diameter of the cutting tool for performing the mold processing. Can be easily processed.

  The step of welding and bonding the first substrate and the second substrate includes, for example, laminating the second substrate on the welding rib, and then melting the welding rib by heating, laser irradiation, ultrasonic irradiation, or the like. It can be performed by a method of pressing from above and below. Especially, it is preferable that the welding rib is melted by ultrasonic irradiation.

  10 recesses, 10a fine recesses, 11, 11a, 11b partition walls, 30, 30a, 30b welding ribs (before substrate bonding), 40, 40a, 40b welding ribs (after substrate bonding), 50 additional recesses, 100th 1 substrate, 151 sample tube placement unit, 152 flow restriction unit, 153 separation unit, 154, 155 liquid reagent holding unit, 156 sample measuring unit, 157, 158 liquid reagent measuring unit, 159, 160, 161, 162 mixing unit, 163 Detection unit, 164, 165 Waste liquid storage unit, 166, 167 Reagent injection port, 200 second substrate, 301 first mold member, 302 second mold member, 310 parting line.

Claims (5)

A first substrate having a recess defined by a partition wall on at least one surface;
A second substrate bonded onto the surface of the first substrate;
A fluid circuit comprising a space constituted by the first substrate side surface of the recess and the second substrate;
Including
The first substrate and the second substrate are welded and bonded via the welding rib provided on the second substrate side surface in at least a part of the partition wall,
The recess includes a fine recess having a width of 0.2 mm or less and / or a depth of 0.2 mm or less, and the width of the welding rib provided on the partition wall defining the fine recess is The microchip which is 0.5 mm or less in a state where the first substrate and the second substrate are bonded to each other. It is a microchip that moves liquid in the fluid circuit by applying centrifugal force in the fluid circuit,
The fluid circuit includes at least one part selected from the group consisting of a part for limiting the flow rate of the liquid, a part for measuring the liquid, and a part for separating the liquid into components.
The microchip according to claim 1, wherein the at least one portion is configured by the fine recess. Forming a first substrate having a concave portion partitioned by a partition wall on at least one surface and having a welding rib on the second substrate side surface in at least a part of the partition wall using a mold;
A step of welding and bonding the first substrate and the second substrate through the welding rib;
Including
The manufacturing method in which at least a part of the welding ribs is formed as a transfer structure of the surface shape of the mold member in a portion along a parting line of at least two mold members used in combination.   The manufacturing method according to claim 3, wherein a maximum width of the at least some welding ribs is less than 0.3 mm before the welding and bonding step.   The manufacturing method of Claim 3 or 4 whose angle of the front-end | tip of the said at least one welding rib is 10-90 degrees.