JPWO2012057099A1 - Microchip - Google Patents

Abstract

Provided is a microchip capable of achieving both improvement in thermal responsiveness in a reaction chamber and securing of bonding strength between a cover member and a substrate. A substrate having a channel groove and a reaction chamber recess communicated by the channel groove on one surface, and a cover member thermally bonded to the one substrate surface. A thin-walled portion that is thinner than the other portions is provided over a range including only a portion of the reaction chamber recess.

Description

  The present invention relates to a microchip usable for PCR.

  Conventionally, a micro-channel that uses microfabrication technology to form fine channels and circuits on a silicon or glass substrate to perform chemical reactions, separation, and analysis of a liquid sample such as nucleic acid, protein, or blood in a minute space A device called a chip (also referred to as a micro analysis chip or a microfluidic chip) or a μTAS (Micro Total Analysis Systems) using a microchip has been put into practical use. According to such a microchip, the amount of sample and reagent used or the amount of waste liquid discharged can be reduced, and an inexpensive system that can be carried in a small space can be realized.

  The microchip is manufactured by bonding two members that have been subjected to fine processing on at least one member. In recent years, resin microchips have been proposed for easy and low-cost manufacturing. More specifically, in order to manufacture a resin microchip, a resin substrate having a channel groove on the surface and a reaction chamber recess communicated by the channel groove, and a channel groove And a resin cover member (for example, a film) that covers the reaction chamber recess. In such a substrate, a through-hole penetrating in the thickness direction is formed at the end of the channel groove or the like. Then, the cover member is joined to the substrate having the channel groove and the reaction chamber recess on the surface with the channel groove and the reaction chamber recess inside. At this time, the substrate and the cover member are preferably thermally bonded. This is because when an adhesive is used for joining the cover member and the substrate, the adhesive tends to enter the flow path or the reaction chamber, causing problems such as narrowing the flow path or reacting with the introduced sample. by. By this bonding, the cover member functions as a lid for the channel groove and the reaction chamber recess, the channel is formed by the channel groove and the cover member, and the reaction chamber is formed by the reaction chamber recess and the cover member. Is formed. Thereby, the microchip which has a flow path and a reaction chamber inside is manufactured. Further, the flow path and the outside of the microchip are connected by a through hole formed in the substrate, and a liquid sample is introduced and discharged through the through hole.

  With such a microchip, gene analysis using PCR (polymerase chain reaction) or electrophoresis can also be performed. In the PCR method, a solution containing double-stranded DNA is denatured into single-stranded DNA by heating at a high temperature (eg, about 95 degrees), and then the solution containing single-stranded DNA is treated, for example, at about 60 degrees. Let cool down. Thereby, a primer couple | bonds with a part of long single stranded DNA (annealing). When this solution is heated again to a temperature suitable for the activity of the DNA polymerase (for example, about 72 ° C.) without separation of the primer, DNA complementary to the single-stranded portion starts from the portion where the primer is bound. Synthesized. By performing a heat cycle operation in which such heating / cooling steps are repeated in a short cycle, DNA synthesis can be repeated and target DNA can be amplified and cultured (gene amplification).

  A heater is provided in accordance with the position of the microchip flow path or predetermined reaction chamber in which this PCR is performed, and the temperature of the heater is appropriately changed and controlled to heat and cool the liquid sample introduced from the through hole. Is done.

  However, many of the resins used for microchips have low thermal conductivity. Thus, Patent Document 1 discloses a technique for increasing the thermal conductivity by making the thickness of the substrate portion including the PCR reaction portion thinner than the thickness of other portions. Patent Document 2 discloses a technique in which a substrate part including at least a PCR channel part is formed into a thin plate, and a spacer resin film from which a channel is cut out is sandwiched between two thin resin films. A technique for forming a microchip that can be used in the process and facilitating heat transfer to a sample is disclosed.

JP 2006-223126 A JP 2006-81406 A

  However, if the substrate is formed thinner than other parts over the entire reaction chamber or beyond for the purpose of enhancing thermal response, sufficient press will be applied at the periphery of the reaction chamber during thermal bonding. It will disappear. As a result, the substrate and the cover member are not reliably bonded to each other, or the bonding strength is insufficient, thereby causing a problem that the sample leaks and adversely affects the analysis. In addition, when thermal bonding is performed using only a thin film without using a substrate, there arises a problem that the strength of the press at the time of thermal bonding cannot be increased, or the reaction chamber and the flow path are blocked by the film.

  The present invention has been made in view of the above circumstances, and provides a microchip capable of achieving both improvement in thermal response in a reaction chamber and securing of bonding strength between a cover member and a substrate. It is intended.

In order to solve the above-mentioned problem, the invention described in claim 1
A substrate provided with a channel groove and a reaction chamber recess communicated by the channel groove on one surface, and a cover member thermally bonded to the one surface of the substrate,
The microchip is characterized in that the substrate is provided with a thin-walled portion that is thinner than other portions over a range including only a portion of the reaction chamber recess.

The invention according to claim 2 is the microchip according to claim 1,
The thin-walled portion is characterized by a cylindrical shape having a bottom circle with the maximum area that can be formed within the range of the reaction chamber recess.

The invention described in claim 3 is the microchip according to claim 1 or 2,
The thin portion is formed by providing a concave portion on the other surface of the substrate.

The invention according to claim 4 is the microchip according to claim 1 or 3,
The thin-walled portion is provided in a range not including the channel groove.

The invention according to claim 5 is the microchip according to claim 1,
The thin-walled portion is formed so that each of the thin-walled portions includes only a part of the concave portion for the reaction chamber at a plurality of locations on the substrate.

The invention according to claim 6 is the microchip according to claim 1,
The thin-walled portion is provided within the range of the recess for the reaction chamber.

The invention according to claim 7 is the microchip according to claim 1 or 5,
The thin-walled portion has a cylindrical shape.

The invention according to claim 8 is the microchip according to claim 1,
The thin-walled portion has a constant thickness.

  According to the present invention, in the microchip, there is an effect that it is possible to achieve both improvement in thermal responsiveness in the reaction chamber and securing of bonding strength between the film and the substrate.

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 top view which shows schematic structure of a microchip. It is a perspective view which shows the internal shape seen from the side of the microchip. It is a perspective view which shows the internal shape seen from the side of the microchip. It is a top view which shows schematic structure of a microchip. It is a perspective view which shows the internal shape seen from the side of the microchip. It is a perspective view which shows the internal shape seen from the side of the microchip. It is a top view which shows schematic structure of a microchip. It is a perspective view which shows the internal shape seen from the side of the microchip. It is a perspective view which shows the internal shape seen from the side of the microchip. It is a top view which shows the modification of schematic structure of a microchip. It is sectional drawing which shows the modification of schematic structure of a microchip. It is sectional drawing which shows the modification of schematic structure of a microchip. It is sectional drawing which shows the modification of schematic structure of a microchip. It is sectional drawing which shows the modification of schematic structure of a microchip. It is sectional drawing which shows the modification of schematic structure of a microchip. It is a top view which shows the modification of schematic structure of a microchip. It is sectional drawing which shows the modification of schematic structure of a microchip. It is sectional drawing which shows the modification of schematic structure of a microchip.

  Hereinafter, the present invention will be described based on the illustrated embodiment, but the present invention is not limited to the embodiment.

[First Embodiment]
(1. Inspection device)
First, an inspection apparatus according to an embodiment of the present invention will be described with reference to FIGS. 1 and 2.
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 is loaded with a microchip 2 from the tray 10 by a tray 10 for placing a microchip 2 into which a specimen, a reagent, and the like have been injected in advance, and a loading mechanism (not shown). A transport port 11, an operation unit 12 for inputting inspection contents, inspection 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 micropump 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 when a medium, a specimen, a reagent, or the like has been injected into the microchip in advance, liquid feeding using a driving liquid is unnecessary, and only the micropump may be operated to assist the movement of the medium. Alternatively, a micropump may be used only for inputting 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 sequentially changes the sample in the microchip 2 to a plurality of predetermined temperatures (for example, three temperatures of about 95 ° C. heat denaturation temperature, about 55 ° C. annealing temperature, and about 70 ° C. polymerization temperature). Heat / cool. The heating unit 15 includes a heating element that increases the temperature by energizing a heater, a Peltier element, and the like, a water-cooling element that decreases the temperature by passing water, and the like. The heating element and the water-cooling element are disposed so as to be in contact with a thin portion 202 of the substrate 3 described later, and perform gene amplification by the PCR method by heating a liquid sample inside the reaction chamber 201 of the substrate 3 described later. The set temperature of the heating unit 15 depends on the thickness of the thin portion 202, but when the sample is heated to 95 ° C, for example, the set temperature is raised to 110 ° C. Further, by providing a heating element or a water cooling element also on the upper side of the film 4, the sample may be heated from both sides so as to sandwich the reaction chamber 201.

(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 come into contact with the energizing unit 40 described later to apply a voltage to the liquid sample via the energizing unit 40. By applying the voltage, 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 FIGS. 3A to 3C.
FIG. 3A is a plan view showing the microchip 2. 3B and 3C are perspective views showing the internal shape of the microchip 2 viewed from the side.

  As shown in FIGS. 3A and 3B, the microchip 2 includes a substrate 3 and a film 4 which are bonded to each other.

  The substrate 3 has a channel groove 30 and a reaction chamber recess 301 on a bonding surface to the film 4 (hereinafter referred to as an inner side surface 3A). The channel groove 30 forms the microchannel 20 in cooperation with the film 4 when the substrate 3 and the film 4 are bonded, and the reaction chamber recess 301 is formed between the substrate 3 and the film 4. And the reaction chamber 201 is formed in cooperation with the film 4. The reaction chamber 201 communicates with the fine flow path 20. In the fine channel 20, a detection region 200 is provided as a target substance detection target region by the detection unit 16 of the inspection apparatus 1. The reaction chamber 201 is an area where PCR is performed by heating by the heating unit 15 of the inspection apparatus 1. The shape of the fine channel 20 (the channel groove 30) is such that the amount of analysis sample and reagent used can be reduced, and the width, depth, etc. can be taken into consideration, such as the fabrication accuracy of molds, transferability, and releasability. In addition, the value is preferably in the range of 10 μm to 200 μm, but is not particularly limited. The width and depth of the fine channel 20 may be determined according to the use of the microchip. The cross-sectional shape of the microchannel 20 may be rectangular or curved, but in consideration of the ease of pressing when performing thermal bonding at both sides of the microchannel 20 and the peripheral portion of the reaction chamber 201. Thus, it is preferable to provide a clear boundary for the film 4. The shape of the reaction chamber 201 is not particularly limited, but the microchip 2 of the present embodiment is elliptical. The depth of the reaction chamber 201 (reaction chamber recess 301) is preferably a value within the same range as the depth of the microchannel 20, but should be different from the depth of the microchannel 20. Is possible. In the microchip 2 of this embodiment, the depth of the reaction chamber 201 is formed deeper than the depth of the microchannel 20.

  Further, the substrate 3 has a plurality of through holes 31 penetrating in the thickness direction. These through-holes 31 are formed at end portions or midway portions of the flow channel groove 30, and connect the fine flow channel 20 and the outside of the microchip 2 when the substrate 3 and the film 4 are bonded together. Opening 21 to be formed is formed. The opening 21 is connected to a chip connecting part 141 (for example, a tube or a nozzle) provided in the liquid feeding part 14 of the inspection apparatus 1 and introduces a gel, a liquid sample, a buffer solution, or the like into the fine channel 20. Or is discharged from the fine channel 20. In addition, an electrode (not shown) of the voltage application unit 18 in the inspection apparatus 1 can be inserted into the opening 21. The shape of the opening 21 (through hole 31) may be various shapes other than a circular shape and a rectangular shape. Further, for example, as shown in FIG. 3C, the periphery of the through hole 31 is projected in a cylindrical shape on the surface opposite to the inner surface 3A (hereinafter referred to as the outer surface 3B) of the substrate 3 to connect the chip connecting portion 141. It may be easy to do.

  On the back side of the reaction chamber 201, a thin portion 202 is formed that is thinner than other portions of the substrate 3 by providing a gap portion 203. The thin portion 202 and the gap 203 are formed in a columnar shape in the microchip 2 of the present embodiment. Further, the size of the thin portion 202 is smaller than the size of the reaction chamber 201.

  The film 4 is a cover member in the present invention. The cover member may be provided with a channel groove or hole, but it is preferable that the cover member does not become too thick in order to ensure bonding with the substrate. When necessary depending on the specimen, reagent, or type of test, the electrode of the voltage application unit 18 is inserted into the opening 21 (through hole 31) and a voltage is applied to the sample in the microchannel 20 for electrophoresis. To do.

  The position and shape of the opening 21 may be in other forms as shown in FIGS. 4A and 4B or FIGS. 5A and 5B, for example. Here, FIG. 4B and FIG. 5B are perspective views showing an internal shape of a portion surrounded by a thick line in FIG. 4A and FIG. 5A when viewed from the side. In the microchip 2 of FIGS. 4A and 4B, the conductive current-carrying portion 40 is provided from the position facing the through hole 31 to the edge of the film 4 in the surface facing the substrate 3 in the film 4. Yes. The energization unit 40 may be patterned on the film 4 by printing or the like. According to such a microchip 2, a voltage is applied to the fluid in the microchannel 20 from the edge of the film 4 via the energization unit 40 without inserting an electrode into the through hole 31 (opening 21). (Refer to the arrow symbol on the right side in FIG. 4B), even when a plurality of microchips 2 are used sequentially, a liquid sample adheres to the electrodes and is mixed into the next microchip 2. Can be prevented. Moreover, in the microchip 2 of FIG. 5A and FIG. 5B, while the through-hole 31 is provided along with each edge part of the groove | channel 30 for flow paths, and the adjacent position of the said edge part, the electricity supply part 40 is 2 adjacent. It is provided over the opposing position of the two through holes 31. According to such a microchip 2, a liquid sample or the like is supplied / discharged using the through hole 31 (opening 21) at the end of the channel groove 30 (see the arrow symbol on the left side in FIG. 5B). ), It is possible to apply a voltage from the adjacent through hole 31 (opening 21) to the fluid in the microchannel 20 via the energization unit 40 (see the arrow symbol on the right side in FIG. 5B). Even when the chips 2 are used in order, it is possible to prevent the liquid sample from adhering to the electrodes and being mixed into the next microchip 2. Even in these cases, as shown in FIGS. 4C and 5C, the outer surface 3 </ b> B of the substrate 3 protrudes in a cylindrical shape around the through hole 31 to facilitate the connection of the chip connecting portion 141. good.

  Further, 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. In addition, the plate thickness of the substrate 3 having the channel groove 30 is preferably 0.2 mm to 5 mm, more preferably 0.5 mm to 2 mm in consideration of moldability. The thickness of the film 4 functioning as a lid (cover) for covering the channel groove is preferably 30 μm to 300 μm, and more preferably 50 μm to 150 μm. Further, the thickness of the thin portion of the substrate 3 is preferably 0.1 mm to 1 mm, that is, it is preferably set thicker than the film 4.

  Moreover, the board | substrate 3 and the film 4 are formed with resin. With respect to the resin used for the substrate 3 and the film 4, conditions such as good moldability (transferability and releasability), high transparency, and low autofluorescence with respect to ultraviolet rays and visible light can be mentioned as conditions. Further, the resin used for the substrate 3 is required to have heat resistance against the heating temperature during PCR. For example, a thermoplastic resin is used for the film 4. Examples of the thermoplastic resin include polycarbonate, polymethyl methacrylate (PMMA), polystyrene, polyacrylonitrile, polyvinyl chloride, polyethylene terephthalate, nylon 6, nylon 66, polyvinyl acetate, polyvinylidene chloride, polypropylene, polyisoprene, and polyethylene. Polydimethylsiloxane, cyclic polyolefin, etc. are preferably used. Particular preference is given to using polycarbonate, polymethyl methacrylate, cyclic polyolefin. For the substrate 3, for example, polycarbonate is used. The same material may be used for the substrate 3 and the film 4, or different materials 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.

  Moreover, the board | substrate 3 and the film 4 are joined by heat sealing | fusion (thermal joining). 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. Preferably, using a hot press machine, the substrate 3 and the film 4 are sandwiched by a heated hot plate, and the substrate 3 and the film 4 are bonded together by applying pressure with the hot plate and holding it for a predetermined time. As a result, the film 4 functions as a lid (cover member) for the flow channel groove 30, and the micro flow channel 20 is formed by the flow channel groove 30 and the film 4, whereby the microchip 2 is manufactured. Note that in order to heat-bond the substrate 3 and the film 4, it is only necessary to heat the interface between the substrate 3 and the film 4, and there is a possibility that only the interface can be heated by using ultrasonic waves, vibrations, and lasers.

  As described above, according to the microchip 2 of the embodiment of the present invention, the substrate 3 provided with the channel groove 30 and the reaction chamber recess 301 communicated by the channel groove 30, and the substrate 3 The microchip 2 is formed by including the film 4 bonded to the surface provided with the channel 30 and the reaction chamber recess 301, and the substrate 3 has the reaction chamber recess 301 (reaction chamber 201). Since the thin part 202 having a thinner thickness than the other part of the substrate 3 is provided over a range including only a part, the liquid sample is heated when the liquid sample in the reaction chamber 201 is heated to perform PCR. Heat can be transferred efficiently. At the same time, since at least a part of the peripheral edge of the reaction chamber recess 301 is formed with the normal thickness of the substrate 3, a necessary press is applied when the substrate 3 and the film 4 are thermally bonded. Therefore, a sufficient bonding strength can be obtained between the substrate 3 and the film 4.

  In addition, the thin wall portion 202 and the gap portion 203 have a cylindrical shape having a bottom circle with the maximum area that can be formed within the range of the reaction chamber recess 301, thereby providing sufficient bonding strength between the substrate 3 and the film 4. As well as having a shape that can be easily processed and provided in the range of the reaction chamber recess 301, the heat of the heater can be efficiently transmitted to the reaction chamber 201.

  Further, the thin wall portion 202 can be easily formed by forming the void portion 302 (concave portion) on the surface of the substrate 3 where the channel groove 30 and the reaction chamber concave portion 301 are not provided. .

  Moreover, the thin-walled portion 202 is provided in a range not including the channel groove 30, so that the bonding strength of the microchannel 20 can be sufficiently secured together with the reaction chamber 201.

[Modification 1]
Next, a modification of the microchip of the above embodiment will be described.
6A to 6C are a plan view and a cross-sectional view of a range including the reaction chamber 201a in the microchip 2 of the first modification.

  As shown in the plan view of FIG. 6A, the microchip 2 of Modification 1 is provided with reaction chambers 201 a connected to these openings 21 between the two openings 21. The shape of the bottom surface of the reaction chamber 201a in the microchip 2 of Modification 1 is a rectangle. Further, a thin portion 202a is provided on the back side of the reaction chamber 201a. The thin portion 202a has a diameter shorter than the long side of the bottom surface of the reaction chamber 201a and longer than the short side. Further, a part of the fine channel 20 is included in the range of the reaction chamber 201a on the cutting line C10. Other configurations are the same as those of the microchip 2 of the first embodiment, and the same reference numerals are given and names are omitted. The configuration of the lower half of the microchip 2 is the same as that of the microchip 2 of the embodiment, and the description is omitted.

  6B is a cross-sectional view of the microchip 2 of Modification 1 along the cutting line C10 of FIG. 6A. FIG. 6C is a cross-sectional view of the microchip 2 of Modification 1 along the cutting line C11 in FIG. 6A.

  As shown in FIG. 6B, on the cutting line C10, the left opening 21 (through hole 31) and the reaction chamber 201a (reaction chamber recess 301a) are communicated with each other by the fine channel 20 (channel groove 30). ing. In addition, a thin portion 202a and a gap portion 203a are provided in the upper part of the reaction chamber 201a. The width of the thin portion 202a is longer than the width of the reaction chamber 201a. On the other hand, as shown in FIG. 6C, the short side of the reaction chamber 201 a is connected to the fine channel 20 on the cutting line C <b> 11. Further, the width of the thin portion 202a at the top of the reaction chamber 201a is shorter than the width of the reaction chamber 201a.

  Thus, even when the thin-walled portion 202a has a width that is partially wider than the reaction chamber recess 301a, the entire reaction chamber recess 301a is not the entire reaction chamber but includes only a part of the reaction chamber recess 301a. Since the thin-walled portion 202a having a thickness smaller than that of the portion is provided, the width of the thin-walled portion 202a is smaller than the width of the recess 301a for the reaction chamber, and the thermal bonding is performed using the peripheral portion of the other reaction chamber 201a. Enough press can be applied. Accordingly, the thermal bonding between the substrate 3 and the film 4 can be reliably performed, and the bonding strength between the substrate 3 and the film 4 can be ensured. In addition, by making the fine channel 20 included in the range of the thin wall portion 202a a part of at most, it is possible to sufficiently secure the bonding strength of the fine channel 20 at the same time as the bonding strength at the peripheral portion of the reaction chamber 201a. it can.

[Modifications 2 to 4]
FIG. 7A to FIG. 7C are diagrams showing modified examples of the shape of the thin-walled portion by cross-sectional views taken along the cutting line C10 in FIG. 6A.

  As shown in FIG. 7A, in the microchip 2 of Modification 2, the thickness of the thin portion 202b of the substrate 3 is small near the approximate center of the reaction chamber 201a due to the truncated cone-shaped gap portion 203b. At the periphery, the thickness of the substrate 3 gradually increases as the distance from the approximate center of the reaction chamber 201a increases. Alternatively, the shape of the gap 203b may be a truncated pyramid.

  Further, as shown in FIG. 7B, in the microchip 2 of the third modification, the thickness of the substrate 3 is thinnest at the approximate center of the reaction chamber 201a and toward the peripheral portion of the thin portion 202c due to the hemispherical gap 203c. Thus, the thickness of the substrate 3 gradually increases. Alternatively, the shape of the gap 203c may be a paraboloid, a hyperboloid, an ellipsoid, or the like.

  As described above, by changing the shape of the thin portion 202c to various shapes, the shape of the heater can be adapted, or the sample in the reaction chamber 201a can be heated in a balanced manner.

  Further, as shown in FIG. 7C, in the microchip 2 of Modification 4, a plurality of irregularities are provided on the upper surface of the thin portion 202d. The shape of the unevenness can be arbitrarily set. By providing such unevenness, the surface area of the upper surface of the thin portion 202d is increased, and the sample in the reaction chamber 201a can be heated more efficiently.

[Modification 5]
8A to 8C are a plan view and a cross-sectional view showing a thin portion provided around the reaction chamber of the substrate in the microchip of Modification 5.

  FIG. 8A is a plan view of the microchip 2 of Modification 5. FIG. In the microchip 2 of Modification 5, the substrate 3 is provided with eight thin portions 202e to 202l. These thin-walled portions 202e to 202l are all smaller in area than the reaction chamber 201a, and all of the thin-walled portions 202e to 202l are located on the upper surface of the reaction chamber 201a. Other configurations are the same as those of the microchip 2 of the embodiment, and the same reference numerals are given and description thereof is omitted. The configuration of the lower half of the microchip 2 is the same as that of the microchip 2 of the embodiment, and the description is omitted.

  8B is a cross-sectional view of the microchip 2 taken along the cutting line C12 shown in FIG. 8A. 8C is a cross-sectional view of the microchip 2 taken along the cutting line C13 shown in FIG. 8A.

  As shown in FIG. 8B, the cross section along the cutting line C12 includes two thin portions 202h and 202i. In this cross section, the two thin portions 202h and 202i are provided across the peripheral edge (long side) of the reaction chamber 201a. On the other hand, as shown in FIG. 8C, the cross section along the cutting line C13 includes a thin portion 202j. The thin portion 202j is entirely located within the reaction chamber 201a. Therefore, a sufficient press pressure can be applied to the peripheral portion of the reaction chamber 201a on the left and right and above in FIG.

  As described above, the thin-walled portions 202e to 202l are formed at a plurality of locations on the substrate 3 so that each includes only a part of the reaction chamber recess 301a, so that the entire area of the thin-walled portion is the area of the reaction chamber recess 301a. The thin part can be formed without being too large compared to the above, and the sample in the reaction chamber 201a can be heated in a well-balanced manner. In particular, the thin-walled portions 202e to 202l are all cylindrical, so that even if the shape of the bottom surface of the reaction chamber 201a deviates greatly from a circle, the thin-walled portions can be easily and well-balanced by simple processing. be able to.

  The present invention is not limited to the above-described embodiment, and various modifications can be made. For example, although the reaction chamber connected to the fine channel is provided in the present embodiment, even when a part of the fine channel is used as the reaction unit, the reaction chamber can be applied to the reaction unit. In addition, when there are a plurality of reaction chambers, a thin portion can be formed for each reaction chamber.

  Moreover, in the said embodiment, although the space | gap part was formed by providing a recessed part in the back side of a reaction chamber, it is also possible to form a hollow space | gap part by providing the bent hole, for example.

  In the above-described embodiment, the heating when using the PCR method has been described. However, the present invention can be applied to those requiring heating even for uses other than the PCR method. In addition, the details shown in the embodiment of the present invention, such as the arrangement of the fine flow path and reaction chamber on the microchip and the shape of the opening, can be appropriately changed without departing from the spirit of the present invention.

Industrial applicability

  The present invention can be used for a microchip that can be used for PCR.

DESCRIPTION OF SYMBOLS 1 Inspection apparatus 2 Microchip 3 Board | substrate 3A Inner side surface 3B Outer side surface 4 Film 10 Tray 11 Transport port 12 Operation part 13 Display part 14 Liquid supply part 140 Micropump 141 Chip connection part 142 Drive liquid tank 143 Drive liquid supply part 146 Drive liquid DESCRIPTION OF SYMBOLS 15 Heating part 16 Detection part 17 Drive control part 18 Voltage application part 20 Fine flow path 21 Opening part 30 Flow path groove 301, 301a Reaction chamber concave part 31 Through-hole 40 Current supply part 200 Detection area 201, 201a Reaction chamber 202, 202a ~ 202l Thin part 203, 203a ~ 203l Cavity part

Claims (8)

A substrate provided with a channel groove and a reaction chamber recess communicated by the channel groove on one surface, and a cover member thermally bonded to the one surface of the substrate,
The microchip according to claim 1, wherein the substrate is provided with a thin portion that is thinner than other portions over a range including only a portion of the recess for the reaction chamber. The microchip according to claim 1, wherein the thin portion has a cylindrical shape having a bottom circle with a maximum area that can be formed within the range of the reaction chamber recess. The microchip according to claim 1, wherein the thin portion is formed by providing a concave portion on the other surface of the substrate. The microchip according to claim 1, wherein the thin portion is provided in a range not including the channel groove. 2. The microchip according to claim 1, wherein the thin portion is formed so as to include only a part of the reaction chamber recess at each of a plurality of locations on the substrate. The microchip according to claim 1, wherein the thin portion is provided within a range of the reaction chamber recess. The microchip according to claim 1, wherein the thin portion has a cylindrical shape. The microchip according to claim 1, wherein a thickness of the thin portion is constant.

Images