JP2012095583A - Microchip and method for manufacturing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a microchip that has superior dimensional stability without causing a weld line and plane strain on the periphery of a chamber, heat resistance and superior response of temperature in the chamber in PCR operation and a method for manufacturing the same.SOLUTION: In the microchip 2 that is equipped with a substrate 3 made of a resin and a film 4 bonded to one surface 3A of the substrate 3 in which a plurality of flow channels 20 for introducing a reagent into the inside or discharging the reagent to the outside and a chamber 26 that communicates with the flow channels 20 and performs examination of at least a specimen or a reagent and amplification of a specimen to be a target of analysis and examination are formed by bonding the substrate 3 to the film 4, the substrate 3 is formed by injection molding and the substrate 3 has a gate filling mark 80 formed by a gate 63 of a mold 6 for injection molding. The gate filling mark 80 is arranged far off at the upstream side in a resin injection direction X relatively to a chamber 70 and a plurality of the flow channels 20 are arranged between the chamber 70 and the gate filling mark 80.

Description

  The present invention relates to a microchip and a method for manufacturing the microchip.

A microchip that uses microfabrication technology to form fine channels and circuits on silicon and glass substrates, and to perform chemical reactions, separation, and analysis of liquid samples such as nucleic acids, proteins, or blood in a microspace ( Devices called micro analysis chips and microfluidic chips) or μTAS (Micro Total Analysis Systems) have been put into practical use. According to such a microchip, it is conceivable to realize an inexpensive system that can be carried in a small space because the amount of sample or reagent used or the amount of discharged waste liquid is reduced.

  A polymerase chain reaction method (hereinafter referred to as a PCR method) is known as a gene propagation method for performing genetic diagnosis using such a microchip. In the PCR method, a specimen containing a gene to be amplified is amplified under a plurality of temperature conditions (for example, three temperature conditions of about 95 ° C. heat denaturation temperature, about 55 ° C. annealing temperature, and about 70 ° C. polymerization temperature). The gene can be amplified in large quantities by repeating this cycle many times.

  A microchip with a PCR function used in the PCR method includes a substrate and a cover member (for example, a film) bonded to one surface of the substrate. On one surface of the substrate, a plurality of channel grooves and a chamber recess communicating with the channel grooves are formed. A well through-hole penetrating the other surface of the substrate (the surface opposite to the bonding surface of the cover member) is formed at the end of the channel groove. Then, by joining the cover member to one surface of the substrate, the cover member functions as a channel groove or a lid for the chamber recess, a plurality of channels, a chamber for testing and analyzing reagents and specimens, Is formed. In addition, a well (opening) that connects the flow path and the outside of the microchip is formed by the well through hole. And a reagent is introduce | transduced into a some flow path through a well, or the reagent in a flow path is discharged | emitted outside.

  By the way, it is known that glass, resin, or the like is used as a material for the substrate of the microchip. However, when glass is used, a fine pattern by machining, etching, or the like is applied to each chip. Direct processing is necessary, and mass production is difficult. Therefore, in recent years, development of inexpensive and disposable resin microchips has been particularly desired (see, for example, Patent Document 1).

JP 2006-223126 A

When manufacturing a resin microchip, it can be formed by an injection molding method capable of transferring a fine concavo-convex pattern, and is formed by injecting molten resin into a mold and cooling.
However, in a microchip with a PCR function, the chamber needs to have a certain volume because of the PCR operation. For example, the depth is about 10 times larger than the flow path. In addition, from the viewpoint of responsiveness of the temperature in the chamber during PCR operation, it is required to make the resin thickness of the portion responsible for heat transfer between the heat cycle heat source such as a heater and chiller and the chamber thinner. That is, in the molding die, a convex chamber molding portion having a negative shape corresponding to the chamber shape for molding the chamber is disposed at a position corresponding to the chamber. The convex chamber molding portion has an extremely larger shape than the convex channel molding portion having a negative shape corresponding to the channel shape for molding the channel. Therefore, if such a large convex chamber molding part is arranged in the middle of the flow of the molten resin, this chamber molding part becomes a barrier, and the flow of the molten resin injected into the mold is blocked. Will be. As a result, the molten resin flows in such a manner as to avoid the outer peripheral portion of the chamber molding that is a thin portion with respect to the plate thickness. Since the mold temperature is very low with respect to the resin temperature, the resin temperature is already filled while being cooled in the filling process. Therefore, a little cooling is performed at the point where the outer periphery of the chamber forming part is joined from the both sides to the substantially central position (on the center line Y (see FIG. 3) passing through the center of the chamber) opposite to the gate. The advanced resin will collide, and a weld line is likely to occur there, and surface distortion is also likely to occur.
The weld line has an adverse effect on the actual use (inspection) results, particularly in terms of stability and reproducibility, when applied to the flow path.Surface distortion can occur during bonding with films and other substrates. It affects the deterioration of responsiveness with the heat cycle heat source during PCR operation. Therefore, a microchip excellent in heat resistance and responsiveness of the temperature in the chamber during PCR operation is required.
The present invention has been made in view of the above circumstances, and is a microchip and a microchip having excellent dimensional stability without causing weld line and surface distortion around the chamber, and excellent thermal responsiveness during PCR operation. The object is to provide a manufacturing method.

According to one aspect of the present invention, a resin substrate, and a cover member bonded to one surface of the substrate,
By joining the substrate and the cover member, a plurality of flow paths for introducing or discharging a reagent to the inside and a chamber communicating with the flow path and amplifying at least a specimen to be examined are formed. In the microchip to be
The substrate is formed by injection molding,
The substrate has a gate filling mark formed by a gate of a molding die for injection molding,
The gate filling mark is disposed farthest upstream in the resin injection direction with respect to the chamber, and the plurality of flow paths are disposed between the chamber and the gate filling mark. A microchip is provided.

According to another aspect of the present invention, comprising: a resin substrate; and a cover member joined to one surface of the substrate;
By joining the substrate and the cover member, a plurality of flow paths for introducing or discharging a reagent to the inside and a chamber communicating with the flow path and amplifying at least a specimen to be examined are formed. In the microchip manufacturing method to be performed,
A molding die for injection molding has a plurality of flow path molding parts for molding the plurality of flow paths, and a chamber molding part for molding the chambers,
The gate is arranged farthest upstream in the resin injection direction with respect to the chamber molding part, and the plurality of flow path molding parts are arranged between the chamber molding part and the gate,
There is provided a method for manufacturing a microchip, wherein the substrate is formed by injecting a resin from a gate of the mold.

  According to the microchip of the present invention, since there is no weld line or surface distortion around the chamber, it is possible to provide a microchip that has excellent heat resistance and does not adversely affect actual use (inspection) results. it can. Furthermore, according to the production method of the present invention, it is possible to produce a microchip having excellent responsiveness with a heat cycle heat source at the time of bonding a substrate and a film or at the time of PCR operation and having the above-described characteristics.

It is a figure which shows the external appearance structure of an inspection apparatus. It is a schematic diagram which shows the internal structure of an inspection apparatus. It is a figure which shows schematic structure of a microchip, (a) is a top view, (b), (c) is arrow sectional drawing at the time of cut | disconnecting along the cutting line II. It is a figure which shows schematic structure of a microchip, (a) is a top view, (b), (c) is arrow sectional drawing at the time of cut | disconnecting along the cutting line II-II. It is a figure which shows schematic structure of a microchip, (a) is a top view, (b), (c) is arrow sectional drawing at the time of cut | disconnecting along the cutting line III-III. It is a side view which shows the shaping | molding apparatus of a board | substrate. It is a sectional side view which shows the shaping | molding die of a board | substrate. (A), (b) is a plane sectional view which shows the shaping | molding die of a board | substrate.

(1. Inspection device)
First, the inspection apparatus according to the present embodiment will be described with reference to FIGS.
FIG. 1 is a perspective view illustrating an example of an external configuration of the inspection apparatus 1, and FIG. 2 is a schematic diagram illustrating an example of an internal configuration of the inspection apparatus 1.

  As shown in FIG. 1, the inspection apparatus 1 includes a tray 10 on which the microchip 2 is placed, a transport port 11 into which the microchip 2 is carried from the tray 10 by a loading mechanism (not shown), and details of inspection and inspection. An operation unit 12 for inputting target data and the like, a display unit 13 for displaying inspection results, and the like are provided.

  Further, as shown in FIG. 2, the inspection apparatus 1 includes a liquid feeding unit 14, a heating unit 15, a voltage application unit 18, a detection unit 16, a drive control unit 17, and the like.

(1-1. Liquid feeding part)
The liquid feeding unit 14 is a unit for feeding the liquid in the microchip 2 and is connected to the microchip 2 carried into the inspection apparatus 1 from the carrying port 11. The liquid feeding unit 14 includes a micro pump 140, a chip connection unit 141, a driving liquid tank 142, a driving liquid supply unit 143, and the like.

Among these, one or more micropumps 140 are provided in the liquid feeding unit 14, and the driving liquid 146 is injected into the microchip 2 or a fluid such as an analysis sample is sucked from the microchip 2. Then, liquid feeding in the microchip 2 is performed. When a plurality of micropumps 140 are provided, each micropump 140 can be driven independently or in conjunction with each other. Note that if a medium, specimen, reagent, etc. are injected into the microchip in advance, the city does not necessarily need to use a driving liquid, and only the micropump can be operated to assist the movement of the medium. Good. A micropump may be used only for the introduction of reagents and specimens.
The chip connection part 141 connects the micropump 140 and the microchip 2 to communicate with each other.

The driving liquid tank 142 stores the driving liquid 146 and supplies it to the driving liquid supply unit 143. The drive liquid tank 142 can be removed from the drive liquid supply unit 143 and replaced for replenishment of the drive liquid 146.
The driving liquid supply unit 143 supplies the driving liquid 146 from the driving liquid tank 142 to the micro pump 140.

  In the liquid feeding unit 14 described above, the microchip 2 and the micropump 140 are connected and communicated with each other by the chip connecting unit 141. When the micropump 140 is driven, the driving liquid 146 is injected into the microchip 2 via the chip connection part 141 or is sucked from the microchip 2. At this time, specimens, reagents, and the like stored in the plurality of storage units in the microchip 2 are sent in the microchip 2 by the driving liquid 146. As a result, the specimen and reagent in the microchip 2 are mixed and reacted, and as a result, inspections such as detection of a target substance and determination of a disease are performed.

(1-2. Heating part)
The heating unit 15 generates heat to heat the microchip 2 to a plurality of specific temperatures. For example, the microchip 2 is heated to three temperatures: a heat denaturation temperature of about 95 ° C., an annealing temperature of about 55 ° C., and a polymerization temperature of about 70 ° C. Thereby, gene amplification by PCR method is performed. The heating unit 15 includes an element that can increase the temperature by energization such as a heater and a Peltier element, an element that can decrease the temperature by water flow, and the like.

(1-3. Voltage application unit)
The voltage application unit 18 has a plurality of electrodes. These electrodes are inserted into the liquid sample in the microchip 2 and directly apply a voltage to the liquid sample, or contact the energizing unit 40 described later and apply a voltage to the liquid sample via the energizing unit 40. As a result, electrophoresis is performed on the liquid sample in the microchip 2.

(1-4. Detection unit)
The detection unit 16 includes a light source such as a light emitting diode (LED) or a laser and a light receiving unit such as a photodiode (PD), and the like, and a target substance contained in a product liquid obtained by a reaction in the microchip 2 is obtained. Optical detection is performed at a predetermined position (a detection area 200 described later) on the microchip 2. The arrangement of the light source and the light receiving unit includes a transmission type and a reflection type, and may be determined as necessary.

(1-5. Drive control unit)
The drive control unit 17 includes a microcomputer, a memory, and the like (not shown), and drives, controls, and detects each unit in the inspection apparatus 1.

(2. Microchip)
Next, the microchip 2 in the present embodiment will be described with reference to FIG.
3A and 3B are diagrams showing a schematic configuration of the microchip 2, in which FIG. 3A is a plan view, and FIG. 3B and FIG. 3C are cross-sectional views taken along the cutting line II.
The microchip in this embodiment is used for PCR as a gene amplification method.

  As shown in FIGS. 3A and 3B, the microchip 2 includes a substrate 3 and a film 4 which are bonded to each other. By bonding the substrate 3 and the film 4, the flow path 20, the chamber 70, the sample introduction flow path 22, the sample discharge flow path 23, the sample introduction port 24, and the sample discharge port 25 are formed inside. The channel 20 includes a first channel 211, a second channel 212, a third channel 213, and a plurality of wells 26.

The substrate 3 is formed by resin injection molding.
The substrate 3 has a first flow path groove 311, a second flow path groove 312, a third flow path groove 313, a plurality of well through holes 36, a chamber recess 71, a sample introduction groove 32, a sample on the bonding surface 3 </ b> A to the film 4. A discharge groove 33, a sample introduction through hole 34, a sample discharge through hole 35, and a detection region 200 are formed.

The first channel groove 311, the second channel groove 312, and the third channel groove 313 are channels for introducing a reagent into or out of the microchip 2.
The first flow path groove 311, the second flow path groove 312 and the third flow path groove 313 cooperate with the film 4 when the substrate 3 and the film 4 are bonded to each other. A channel 212 and a third channel 213 are formed.
The first flow path 211 extends substantially linearly along the front-rear direction (resin injection direction X) of the substrate 3. The two second flow channels 212 communicate with the middle portion of the first flow channel 211, extend in a substantially linear shape along a direction (left-right direction) orthogonal to the first flow channel 211, and are substantially mutually separated. It is parallel. The third flow path 213 communicates with one end of the first flow path 211 (upstream end in the resin injection direction X), and extends substantially linearly along a direction orthogonal to the first flow path 211. is doing.

The plurality of well through holes 36 are formed so as to penetrate in the thickness direction of the substrate 3. The well through holes 36 communicate with both end portions of the second flow path 212 and the third flow path 213, respectively. And when the board | substrate 3 and the film 4 are bonded together, the well 26 (opening part) which connects the 1st-3rd flow paths 211-213 and the exterior of the microchip 2 is formed.
The well 26 is connected to a chip connecting part 141 (tube or nozzle) provided in the liquid feeding part 14 of the inspection apparatus 1 to introduce a reagent into the first to third flow paths 211 to 213, It discharges from the 3rd channel 211-213.
Further, an electrode (not shown) of the voltage application unit 18 in the inspection apparatus 1 can be inserted into the well 26. The well 26 (well through hole 36) has a circular shape when viewed from the thickness direction of the substrate 3.
Further, for example, as shown in FIG. 3C, the periphery of the well through hole 36 is projected in a cylindrical shape on the surface 3B opposite to the surface 3A of the substrate 3 so that the chip connecting portion 141 can be easily connected. good.

The chamber recess 71 communicates with the other end of the first flow path groove 311 (downstream end in the resin injection direction X). Then, when the substrate 3 and the film 4 are bonded together, the chamber 70 is formed in cooperation with the film 4. The chamber 70 communicates with the other end of the first flow path 211 (downstream end in the resin injection direction X). The chamber 70 has an elliptical shape when viewed from the thickness direction of the substrate 3.
The chamber 70 is an area for amplifying at least a specimen to be examined.
Further, as shown in FIGS. 3A and 3C, the surface 3B opposite to the bonding surface 3A of the substrate 3 with the film 4 is located at a position corresponding to the chamber 70 so that the thickness of the substrate 3 is reduced. A thinned portion 38 may be formed. That is, the thickness of the substrate 3 at the position where the chamber 70 is formed is made thinner than the thickness of the substrate 3 at other positions.

One end of the sample introduction groove 32 communicates with the chamber recess 71, and the other end communicates with the sample introduction through hole 34. The sample discharge groove 33 has one end communicating with the chamber recess 71 and the other end communicating with the sample discharge through hole 35. The sample introduction through hole 34 and the sample discharge through hole 35 penetrate the surface 3B opposite to the bonding surface 3A of the substrate 3.
The sample introduction groove 32 and the sample discharge groove 33 form the sample introduction channel 22 and the sample discharge channel 23 in cooperation with the film 4 when the substrate 3 and the film 4 are bonded together. In addition, the sample introduction through hole 34 and the sample discharge through hole 35 connect the sample introduction flow path 22 and the sample discharge flow path 23 to the outside of the macro chip 2 when the substrate 3 and the film 4 are bonded together. A mouth 24 and a specimen outlet 25 are formed.
The sample introduction groove 32 and the sample discharge groove 33 are each curved from the outer periphery of the chamber 70 when viewed from the thickness direction of the substrate 3. The sample introduction through hole 34 and the sample discharge through hole 35 are circular.
The sample introduced from the sample introduction port 24 is introduced into the chamber 70 via the sample introduction flow path 22. The sample in the chamber 70 is discharged from the sample discharge port 25 to the outside of the microchip 2 through the sample discharge channel 23.

  The detection region 200 is provided in the first flow path 211. The detection region 200 is a target substance detection target region by the detection unit 16 of the inspection apparatus 1.

Since such a substrate 3 is formed by injection molding, the substrate 3 is provided with a gate filling mark (gate cut residue) 80 formed by the gate 63 of the injection mold 6.
The gate filling mark 80 is formed on one side surface in the front-back direction of the substrate 3 (upstream side surface in the resin injection direction X). That is, the substrate 3 is formed on the side surface opposite to the side surface on the chamber 70 side. Further, the gate filling mark 80 is disposed farthest upstream in the resin injection direction X with respect to the chamber 70, and the first to third flow paths 211 to 213 and the chamber 70 and the gate filling mark 80 are arranged between the chamber 70 and the gate filling mark 80. A plurality of wells 26 are arranged.

In the microchip 2 as described above, when viewed from the thickness direction of the substrate 3, the chamber 70, the well 26, the sample introduction channel 22, the sample discharge channel 23, the sample introduction port 24, and the sample discharge port 25 are gates. It passes through the center of the filling mark 80 and is symmetrical with respect to the center line Y along the resin injection direction X. That is, it is symmetrical with respect to the center line Y.
The chamber 70, the first to third channels 211 to 213, the well 26, the sample introduction channel 22, the sample discharge channel 23, the sample introduction port 24, and the sample discharge port 25 are viewed from the thickness direction of the substrate 3. The shape of the case is not limited to the shape shown in FIG. 3A, and is preferably symmetrical with respect to the center line Y, and can be changed as appropriate. Moreover, the cross-sectional shape of each flow path and the through hole is not limited to a rectangular shape, and may be a curved surface.
Moreover, it is preferable that the 1st-3rd flow paths 211-213 (1st-3rd flow path grooves 311-313) and the well 26 (well through-hole 36) are 1-1000 micrometers in both width and depth. The sample introduction channel 22 (sample introduction groove 32) and the sample discharge channel 23 (sample discharge groove 33) are 300 to 2000 μm in both width and depth, the sample introduction port 24 (sample introduction through hole 34), and the sample discharge port 25. The (sample discharge through hole 35) is preferably 0.5 to 5 mm in both width and depth, but is not particularly limited.
The depth of the chamber 70 is 10 times or more larger than that of the first to third flow paths 211 to 213, the sample introduction port 24, the sample discharge port 25, and the well 26. However, the depth of the sample introduction flow path 22 and the sample discharge flow path 23 is the same level as the chamber 70, and the width is also 10 times or more that of the first to third flow paths 211 to 213.

  The film 4 is a cover member in the present invention, and has a sheet shape in the present embodiment. In the film 4, an energizing portion 40 is formed at a position facing the well 26. The energization section 40 is electrically charged with the specimens and reagents in the first to third flow paths 211 to 213 by applying a voltage from the electrode of the voltage application section 18 inserted in the well 26 (well through hole 36). Let run.

  The position and shape of the well 26 may be in other forms as shown in FIGS. 4 (a) and 4 (b) and FIGS. 5 (a) and 5 (b). Here, in the microchip 2 of FIG. 4, the conductive current-carrying portion 40 is provided from the position facing the well through hole 36 to the edge of the film 4 on the surface of the film 4 facing the substrate 3. ing. The energization unit 40 may be patterned on the film 4 by printing or the like. According to such a microchip 2, voltage is applied to the fluid in the flow path 20 from the edge of the film 4 via the energization unit 40 without inserting an electrode into the well 26 (well through hole 36). Therefore, even when a plurality of microchips 2 are used in order, it is possible to prevent a sample or reagent from adhering to the electrodes and mixing into the next microchip 2. Further, in the microchip 2 of FIG. 5, the well through holes 36 are provided side by side at the respective end portions of the first to third flow channel grooves 311 to 313 and adjacent positions of the end portions, and the energizing portion 40 is provided. The two well through holes 36 are provided to face each other. According to such a microchip 2, a reagent or the like is introduced / discharged using the well 26 (well through hole 36), and the flow path 20 is passed from the adjacent well 26 (well through hole 36) via the energization unit 40. Since it is possible to apply a voltage to the reagent inside, it is possible to prevent the reagent from adhering to the electrode and mixing into the next microchip 2 even when a plurality of microchips 2 are used sequentially. Can do. Even in these cases, as shown in FIGS. 4C and 5C, the surface 3B opposite to the bonding surface 3A of the substrate 3 protrudes around the well through hole 36 in a cylindrical shape. The chip connection part 141 may be easily connected.

  The outer shape of the substrate 3 and the film 4 may be any shape that can be easily handled and analyzed, and is preferably a square or a rectangle in plan view. As an example, the size may be 10 mm square to 200 mm square. Moreover, the magnitude | size of 10 mm square-100 mm square may be sufficient. Further, the plate thickness of the substrate 3 is preferably 0.2 mm to 5 mm, more preferably 0.5 mm to 2 mm in consideration of moldability. Further, the thickness of the thin portion 38 is preferably about the thickness of the film 4, but is preferably about 0.2 to 1.0 mm in view of moldability. This numerical value is based on the assumption that the thickness of the substrate 3 is 1.5 mm. The thickness of the film 4 that functions as a lid (cover member) of the substrate 3 is preferably 30 μm to 300 μm, and more preferably 50 μm to 150 μm.

  The substrate 3 and the film 4 are formed of resin. The resin used for the substrate 3 and the film 4 includes conditions such as good moldability and bondability, high transparency, and low autofluorescence with respect to ultraviolet rays and visible light (light having a specific wavelength). For example, a thermoplastic resin is used for the substrate 3 and the film 4. Examples of the thermoplastic resin include polycarbonate, polymethyl methacrylate, polystyrene, polyacrylonitrile, polyvinyl chloride, polyethylene terephthalate, nylon 6, nylon 66, polyvinyl acetate, polyvinylidene chloride, polypropylene, polyisoprene, polyethylene, polydimethyl. It is preferable to use siloxane, cyclic polyolefin or the like. Particular preference is given to using polycarbonate, polymethyl methacrylate, cyclic polyolefin. In addition, the same material may be used by the board | substrate 3 and the film 4, and a different material may be used. When the substrate 3 and the film 4 are made of the same type of material, they are compatible with each other, so that they are easily bonded after being melted.

  The substrate 3 and the film 4 are bonded by heat fusion. For example, it joins by heating the board | substrate 3 and the film 4 using a hot plate, a hot air, a hot roll, an ultrasonic wave, a vibration, or a laser. As an example, using a hot press machine, the substrate 3 and the film 4 are sandwiched by a heated hot plate, the pressure is applied by the hot plate and held for a predetermined time, thereby bonding the substrate 3 and the film 4. Thus, the film 4 is covered with the first to third flow channel grooves 311 to 313, the well through hole 36, the sample introduction groove 32, the sample discharge groove 33, the sample introduction through hole 34, the sample discharge through hole 35, and the lid of the chamber recess 71. Functions as a (cover member), and the first to third channels 211 to 213, the well 26, the sample introduction channel 22, the sample discharge channel 23, the sample introduction port 24, the sample discharge port 25, and the chamber 70 are formed. The microchip 2 is manufactured. In order to heat-bond the substrate 3 and the film 4, it is sufficient that only the interface between the substrate 3 and the film 4 can be heated, and there is a possibility that only the interface can be heated by using ultrasonic waves, vibrations, and lasers.

(3. Microchip manufacturing equipment)
Next, an apparatus for manufacturing the microchip 2 will be described.

  The manufacturing apparatus of the microchip 2 is configured to manufacture the microchip 2 by forming the substrate 3 and the film 4 and then bonding them together. As shown in FIG. Etc.

The molding apparatus 5 has a fixed side platen 51 and a movable side platen 52 on a base 50.
The stationary side platen 51 is a flat plate-like member erected on the base 50. Columnar tie bars 53 are provided at the four corners of the fixed side platen 51 and extend perpendicular to the fixed side platen 51.

  The movable side platen 52 is a flat plate-like member disposed to face the fixed side platen 51, and is supported at four corners by tie bars 53 provided on the fixed side platen 51. The movable platen 52 is guided by a tie bar 53 and is movable in a horizontal direction (in the direction of arrows A and A ′ in the drawing), that is, in a contact / separation direction with respect to the fixed platen 51 by a drive mechanism (not shown). .

  A molding die 6 is disposed between the fixed platen 51 and the movable platen 52 described above. When the movable platen 52 moves in the direction of arrow A, the molding die 6 is clamped, and the movable platen is moved. The mold 6 is opened by moving 52 in the direction of the arrow A ′.

(3-1. Mold)
FIG. 7 is a cross-sectional view showing a schematic configuration of the mold 6 and shows a state in which the cavity 64 is filled with the molten resin J. FIG.
As shown in FIG. 7, the mold 6 is an injection mold including a fixed mold 60 and a movable mold 61 provided so as to be able to contact and separate from the fixed mold 60. When the fixed mold 60 and the movable mold 61 are brought into contact with each other, a cavity 64 for molding the molten resin J into the shape of the substrate 3 and a runner 62 and a gate 63 for introducing the molten resin J into the cavity 64 are formed. It is supposed to be. An injection unit is connected to the runner 62 through a sprue (not shown), and the cavity 64 is filled with the molten resin J through the gate 63 from the runner 62.

Here, the fixed mold 60 is for forming the joint surface 3 </ b> A of the substrate 3 with the film 4 and is fixed to the fixed platen 51. In addition, in FIG. 7, although a mode that the center part and outer peripheral part of the fixed mold | type 60 were comprised with a different member is illustrated, it is good also as comprising with a single member.
As shown in FIG. 8A, the fixed mold 60 has protrusions corresponding to the shapes of the first to third flow grooves 311 to 313 at positions corresponding to the first to third flow grooves 311 to 313. A first to third flow path forming part 630a having a shape is provided. Further, the fixed mold 60 has a convex well forming portion which is a portion for receiving a well through hole forming pin provided in the movable mold 61 corresponding to the well through hole 36 at a position corresponding to the well through hole 36. 630b is provided.
In addition, a convex chamber forming portion 671 having a negative shape corresponding to the shape of the chamber recess 71 is provided at a position corresponding to the chamber recess 71 of the fixed mold 60.
The gate 63 is disposed farthest upstream in the resin injection direction X with respect to the chamber molding portion 6701. Between the chamber molding portion 671 and the gate 63, the first to third channel molding portions 630a and the wells are arranged. A molding part 630b is arranged.
In addition, the well molding part 630b and the chamber molding part 671 are arranged symmetrically with respect to the center line Z along the resin injection direction X through the center of the gate 63.
Further, an air vent 90 is provided in the cavity 64 at the most downstream position in the resin injection direction X with respect to the gate 63. The air vent 90 may be provided in a straight line shape in a plan view, or may be provided in a U-shape in a plan view as shown in FIG. The air vent 90 is a gap of 5 to 20 μm formed in a state where the fixed mold 60 and the movable mold 61 are closed, and is set to a limit at which resin does not leak by normal injection molding. The air vent 90 may be provided on the fixed mold 60, but is generally provided on the movable mold 61.
The air vent 90 allows the air in the cavity 64 to escape to the outside of the cavity 64 on the downstream side (back side) of the resin injection direction X of the cavity 64 so as to spread the molten resin J.

On the other hand, the movable die 61 forms a surface 3B opposite to the bonding surface 3A of the substrate 3, and is fixed to the movable platen 52.
The movable die 61 has an annular outer peripheral die (usually called “frame core”) 610 and a central die (usually called “core”) 611 fitted inside the outer peripheral die 610. .

  The outer peripheral mold 610 is formed in a cylindrical shape having a molding surface on the inner peripheral portion of the end surface on the fixed mold 60 side, and the outer peripheral portion of the outer surface 3B of the substrate 3 and the side peripheral surface of the substrate 3 are molded. It has become.

  The central die 611 is formed in a columnar shape having a molding surface on the end surface on the fixed die 60 side, and the central portion of the surface 3B opposite to the bonding surface 3A of the substrate 3 is molded.

  The movable mold 61 described above is provided with an eject pin (not shown) that can be projected and retracted from the molding surface so that the molded product is released from the movable mold 61.

(3-2. Microchip manufacturing method)
Then, the manufacturing method of the microchip 2 which manufactures the microchip 2 from the board | substrate 3 using the above shaping | molding die 6 is demonstrated.

  First, the molten resin J is injected from the runner 62 into the gate 63 and the cavity 64 and then molded while being pressurized in the cavity 64. At this time, the air in the cavity 64 escapes from the air vent 90, and the molten resin J can be reliably and easily filled into the cavity 64.

  Next, when the molded product is cooled to a predetermined temperature, the molded product is released from the fixed mold 60 by separating the movable mold 61 from the fixed mold 60.

Next, by ejecting an eject pin from the movable mold 61, the molded product is released from the movable mold 61, and the substrate 3 is manufactured.
A gate filling mark 80 by the gate 63 is formed on the substrate 3 thus manufactured. A chamber recess 71 is formed farthest downstream from the gate filling mark 80 in the resin injection direction X with respect to the first to third flow path grooves 311 to 313 and the well through hole 36. Further, an air vent burr (not shown) may be formed at a position corresponding to the air vent 90.

  Finally, the microchip 2 is manufactured by bonding the separately manufactured film 4 to the bonding surface 3A of the substrate 3 by thermal fusion.

As described above, according to the present embodiment, the substrate 3 has the gate filling mark 80 formed by the gate 63 of the injection mold 6, and the gate filling mark 80 is formed with respect to the chamber 70. A plurality of flow paths 20 (first to third flow paths 211 to 213, wells 26) are disposed between the chamber 70 and the gate filling mark 80, which is disposed farthest upstream in the resin injection direction X. Therefore, the flow of the molten resin J once squeezed by the gate 63 gradually spreads as it fills, and when it reaches the chamber 70, the flow front (the tip of the molten resin flow) is substantially linear. By reaching the chamber 70 in this state, it becomes difficult to be affected by the thinning of the chamber 70, and the microchip 2 in which no weld line or surface distortion occurs around the chamber 70 can be obtained. As a result, the heat resistance is excellent, and a short circuit between the chamber 70 and the other structure (the plurality of flow paths 20) hardly occurs. There is no adverse effect on actual use (inspection) results. Furthermore, it is excellent also in the responsiveness with the heat cycle heat source at the time of joining the board | substrate 3 and the film 4, and the time of PCR operation.
Further, the plurality of flow paths 20 (the wells 26 and the chambers 70 are symmetrical with respect to the center line Y along the resin injection direction X through the center of the gate filling mark 80 when viewed from the thickness direction of the substrate 3. Since it is formed, the molten resin J is filled evenly and uniformly, and the heat resistance and thermal response can be further improved.
Since the thinned portion 38 is formed at a position corresponding to the chamber 70 on the surface 3B opposite to the bonding surface 3A of the substrate 3, the thermal response during PCR operation is very excellent. be able to.

The molding die 6 for injection molding has a plurality of negative-shaped flow path molding portions 630 a and 630 b corresponding to the shapes of the plurality of flow paths 20 and a negative-shaped chamber molding portion 670 corresponding to the shape of the chamber 70. The gate 63 is disposed farthest upstream in the resin injection direction X with respect to the chamber molding portion 671, and a plurality of flow path molding portions 630a and 630b are disposed between the chamber molding portion 671 and the gate 63. Therefore, by using such a molding die 6, the chamber molding portion 71 serving as a barrier for the flow of the molten resin J is not disposed near the gate 63 of the molding die 6. The injected molten resin J is uniformly and evenly flowed and filled in the cavity 64 of the mold 6. Therefore, it is possible to prevent weld lines and surface distortion that are likely to occur around the chamber 70. And it can be excellent in heat resistance and thermal responsiveness.
Since injection molding is performed using the molding die 6 in which the air vent 90 is provided at the most downstream position in the resin injection direction J with respect to the gate 63, the air in the cavity 64 can be removed, and the molten resin J can be surely and easily The cavity 64 can be filled.

  The embodiments to which the present invention can be applied are not limited to the above-described embodiments, and can be appropriately changed without departing from the spirit of the present invention.

2 Microchip 3 Substrate 3A Bonding surface 3B Opposite surface 4 Film (cover member)
6 Mold 20 Channel 38 Thin portion 63 Gate 70 Chamber 80 Gate filling mark 90 Air vent 211 First channel 212 Second channel 213 Third channel 630a First to third channel molding units (channel molding unit)
630b Well molding part (channel molding part)
671 Chamber molding part X Resin injection direction Y, Z Center line

Claims (5)

A resin substrate and a cover member bonded to one surface of the substrate;
By joining the substrate and the cover member, a plurality of flow paths for introducing or discharging a reagent to the inside, and amplification of a sample that is connected to the flow path and is a test or analysis target for at least a sample or a reagent And a microchip on which a chamber is formed,
The substrate is formed by injection molding,
The substrate has a gate filling mark formed by a gate of a molding die for injection molding,
The gate filling mark is disposed farthest upstream in the resin injection direction with respect to the chamber, and the plurality of flow paths are disposed between the chamber and the gate filling mark. To microchip.   The plurality of flow paths and the chambers are formed symmetrically with respect to a center line along the resin injection direction through the center of the gate filling mark when viewed from the thickness direction of the substrate. The microchip according to claim 1.   3. The microchip according to claim 1, wherein a position corresponding to the chamber is thin on a surface of the substrate opposite to a bonding surface with the cover member. 4.   The microchip according to any one of claims 1 to 3, wherein the microchip is injection-molded using the molding die provided with an air vent at a most downstream position in a resin injection direction with respect to the gate. A resin substrate and a cover member bonded to one surface of the substrate;
By joining the substrate and the cover member, a plurality of flow paths for introducing or discharging a reagent to the inside, and amplification of a sample that is connected to the flow path and is a test or analysis target for at least a sample or a reagent And a microchip manufacturing method in which a chamber is formed,
A molding die for injection molding has a plurality of negative-shaped flow path molding portions corresponding to the shapes of the plurality of flow paths, and a negative-shaped chamber molding portion corresponding to the shape of the chamber,
The gate is arranged farthest upstream in the resin injection direction with respect to the chamber molding part, and the plurality of flow path molding parts are arranged between the chamber molding part and the gate,
A method of manufacturing a microchip, wherein the substrate is formed by injecting resin from a gate of the mold.

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