WO2012057099A1 - Micropuce - Google Patents

Micropuce Download PDF

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Publication number
WO2012057099A1
WO2012057099A1 PCT/JP2011/074476 JP2011074476W WO2012057099A1 WO 2012057099 A1 WO2012057099 A1 WO 2012057099A1 JP 2011074476 W JP2011074476 W JP 2011074476W WO 2012057099 A1 WO2012057099 A1 WO 2012057099A1
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WO
WIPO (PCT)
Prior art keywords
microchip
reaction chamber
substrate
thin
film
Prior art date
Application number
PCT/JP2011/074476
Other languages
English (en)
Japanese (ja)
Inventor
毅彦 五島
幹司 関原
Original Assignee
コニカミノルタオプト株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by コニカミノルタオプト株式会社 filed Critical コニカミノルタオプト株式会社
Priority to JP2012540855A priority Critical patent/JP5973350B2/ja
Publication of WO2012057099A1 publication Critical patent/WO2012057099A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1883—Means for temperature control using thermal insulation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0421—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic electrophoretic flow

Definitions

  • the present invention relates to a microchip usable for PCR.
  • 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
  • ⁇ TAS Micro Total Analysis Systems
  • a microchip is manufactured by bonding two members that have been finely processed to at least one member.
  • 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.
  • the substrate and the cover member are preferably thermally bonded.
  • 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
  • the reaction chamber is formed by the reaction chamber recess and the cover member. Is formed.
  • 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.
  • Such a microchip can also perform gene analysis using PCR (polymerase chain reaction) or electrophoresis.
  • PCR polymerase chain reaction
  • 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
  • a temperature suitable for the activity of the DNA polymerase for example, about 72 ° C.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 part of the recess for the reaction chamber.
  • 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.
  • the microchip in the microchip, there is an effect that it is possible to achieve both the improvement of the thermal response in the reaction chamber and the securing of the bonding strength between the film and the substrate.
  • FIG. 1 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.
  • FIG. 1 is a perspective view illustrating an example of an external configuration of the inspection apparatus 1
  • FIG. 2 is a schematic diagram illustrating an example of an internal configuration of the inspection apparatus 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the microchip 2 and the micropump 140 are connected and communicated by the chip connecting part 141.
  • the driving liquid 146 is injected into the microchip 2 via the chip connection part 141 or is sucked from the microchip 2.
  • 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.
  • 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 disease are performed.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the microchip 2 includes a substrate 3 and a film 4 bonded to each other.
  • the substrate 3 has a channel groove 30 and a reaction chamber recess 301 on the 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.
  • the reaction chamber 201 is formed in cooperation with the film 4.
  • the reaction chamber 201 communicates with the fine flow path 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.
  • the value is preferably in the range of 10 ⁇ m to 200 ⁇ m, 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.
  • 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.
  • 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 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.
  • a thin wall 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.
  • 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.
  • 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.
  • FIGS. 4A and 4B or FIGS. 5A and 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.
  • 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.
  • 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).
  • a liquid sample adheres to the electrodes and is mixed into the next microchip 2. Can be prevented.
  • the electricity supply part 40 is 2 adjacent. It is provided over the opposing position of the two through holes 31.
  • 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 energizing 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.
  • 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.
  • the size may be 10 mm square to 200 mm square. Further, the size may be 10 mm square to 100 mm square.
  • the 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 ⁇ m to 300 ⁇ m, and more preferably 50 ⁇ m to 150 ⁇ m.
  • 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.
  • the substrate 3 and the film 4 are made of resin.
  • 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.
  • the resin used for the substrate 3 is required to have heat resistance against the heating temperature during PCR.
  • a thermoplastic resin is used for the film 4.
  • thermoplastic resin examples 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.
  • 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.
  • the substrate 3 and the film 4 are bonded by thermal fusion (thermal bonding).
  • thermal fusion thermal bonding
  • it joins by heating the board
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the heat of the heater can be efficiently transmitted to the reaction chamber 201.
  • 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. .
  • the thin-walled portion 202 is provided in a range that does not include the channel groove 30, so that the bonding strength of the microchannel 20 together with the reaction chamber 201 can be sufficiently secured.
  • the microchip 2 of Modification 1 is provided with reaction chambers 201a 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.
  • 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.
  • 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.
  • FIG. 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.
  • the left opening 21 (through hole 31) and the reaction chamber 201a are communicated with each other by the fine channel 20 (channel groove 30). ing.
  • 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.
  • 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.
  • 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.
  • 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.
  • FIG. 7A to FIG. 7C are views showing modified examples of the shape of the thin-walled portion by cross-sectional views taken along section line C10 in FIG. 6A.
  • 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.
  • the shape of the gap 203b may be a truncated pyramid.
  • 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.
  • the thickness of the substrate 3 gradually increases.
  • the shape of the gap 203c may be a paraboloid, a hyperboloid, an ellipsoid, or the like.
  • the shape of the heater can be adapted, or the sample in the reaction chamber 201a can be heated in a balanced manner.
  • 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. 1 is 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.
  • 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.
  • FIG. 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.
  • the cross section along the cutting line C12 includes two thin portions 202h and 202i.
  • the two thin portions 202h and 202i are provided across the peripheral edge (long side) of the reaction chamber 201a.
  • 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.
  • the thin 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 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.
  • 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 greatly deviates 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 embodiment, and various modifications can be made.
  • 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.
  • a thin portion can be formed for each reaction chamber.
  • the cavity is formed by providing a recess on the back side of the reaction chamber.
  • the heating when using the PCR method has been described.
  • the present invention can be applied to those requiring heating even for uses other than the PCR method.
  • 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.
  • the present invention can be used for a microchip that can be used for PCR.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention porte sur une micropuce qui a à la fois une sensibilité thermique améliorée dans une chambre de réaction et un pouvoir de liaison garantie entre un élément de couvercle et un substrat. La micropuce comprend un substrat qui a une rainure de trajet d'écoulement formée sur une surface de celui-ci et une partie de chambre de réaction concave qui est en communication avec la rainure de trajet d'écoulement et un élément de couvercle qui est lié thermiquement à ladite surface du substrat, une partie mince ayant une épaisseur inférieure à celle de l'autre partie étant formée sur une région qui contient seulement une partie de la partie de chambre de réaction concave est formée dans le substrat.
PCT/JP2011/074476 2010-10-29 2011-10-25 Micropuce WO2012057099A1 (fr)

Priority Applications (1)

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JP2012540855A JP5973350B2 (ja) 2010-10-29 2011-10-25 マイクロチップ

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JP2010-243667 2010-10-29
JP2010243667 2010-10-29

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WO2018216673A1 (fr) * 2017-05-23 2018-11-29 ウシオ電機株式会社 Micropuce

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US20060228258A1 (en) * 2005-04-12 2006-10-12 Chromedx Inc. Blood collection and measurement apparatus
JP2009097902A (ja) * 2007-10-15 2009-05-07 Sony Corp 反応制御装置及び反応制御方法
JP2009119387A (ja) * 2007-11-15 2009-06-04 Fujifilm Corp マイクロ流路内混合方法および装置
JP2009166416A (ja) * 2008-01-18 2009-07-30 Konica Minolta Opto Inc マイクロチップの製造方法、及びマイクロチップ

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JP4695851B2 (ja) * 2003-07-10 2011-06-08 シチズンホールディングス株式会社 マイクロ化学チップ温度調節装置
JP2006234467A (ja) * 2005-02-23 2006-09-07 Yamaha Corp マイクロチップ用の温度制御装置
JP2006246777A (ja) * 2005-03-10 2006-09-21 Canon Inc 生化学反応用カートリッジおよび生化学反応カートリッジ内での溶液の移動方法
JP5303983B2 (ja) * 2008-03-26 2013-10-02 株式会社島津製作所 反応処理方法及び反応処理装置

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Publication number Priority date Publication date Assignee Title
US20060228258A1 (en) * 2005-04-12 2006-10-12 Chromedx Inc. Blood collection and measurement apparatus
JP2009097902A (ja) * 2007-10-15 2009-05-07 Sony Corp 反応制御装置及び反応制御方法
JP2009119387A (ja) * 2007-11-15 2009-06-04 Fujifilm Corp マイクロ流路内混合方法および装置
JP2009166416A (ja) * 2008-01-18 2009-07-30 Konica Minolta Opto Inc マイクロチップの製造方法、及びマイクロチップ

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018216673A1 (fr) * 2017-05-23 2018-11-29 ウシオ電機株式会社 Micropuce
JP2018197663A (ja) * 2017-05-23 2018-12-13 ウシオ電機株式会社 マイクロチップ

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JPWO2012057099A1 (ja) 2014-05-12

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