WO2009131043A1 - Microchip - Google Patents

Microchip Download PDF

Info

Publication number
WO2009131043A1
WO2009131043A1 PCT/JP2009/057573 JP2009057573W WO2009131043A1 WO 2009131043 A1 WO2009131043 A1 WO 2009131043A1 JP 2009057573 W JP2009057573 W JP 2009057573W WO 2009131043 A1 WO2009131043 A1 WO 2009131043A1
Authority
WO
WIPO (PCT)
Prior art keywords
liquid
microchip
dummy
reagent
reagent liquid
Prior art date
Application number
PCT/JP2009/057573
Other languages
French (fr)
Japanese (ja)
Inventor
義一 栗原
継吾 玉木
彰久 中島
理英 村瀬
Original Assignee
コニカミノルタエムジー株式会社
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 コニカミノルタエムジー株式会社 filed Critical コニカミノルタエムジー株式会社
Priority to JP2010509151A priority Critical patent/JPWO2009131043A1/en
Publication of WO2009131043A1 publication Critical patent/WO2009131043A1/en

Links

Images

Classifications

    • 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
    • B01L3/50273—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 means or forces applied to move the fluids
    • 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
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • 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
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/142—Preventing evaporation
    • 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
    • B01L2200/16—Reagents, handling or storing thereof
    • 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
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/025—Displaying results or values with integrated means
    • B01L2300/027—Digital display, e.g. LCD, LED
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • 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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • 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
    • B01L2300/10—Means to control humidity and/or other gases
    • 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
    • B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
    • 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
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • 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
    • B01L3/52—Containers specially adapted for storing or dispensing a reagent
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D81/00—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents
    • B65D81/18—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient
    • B65D81/20—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient under vacuum or superatmospheric pressure, or in a special atmosphere, e.g. of inert gas
    • B65D81/2069—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient under vacuum or superatmospheric pressure, or in a special atmosphere, e.g. of inert gas in a special atmosphere
    • B65D81/2084—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient under vacuum or superatmospheric pressure, or in a special atmosphere, e.g. of inert gas in a special atmosphere in a flexible container
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N2035/00099—Characterised by type of test elements
    • G01N2035/00148—Test cards, e.g. Biomerieux or McDonnel multiwell test cards

Definitions

  • the present invention relates to a microchip having a reagent liquid stored therein.
  • micromachine technology In recent years, by making full use of micromachine technology and ultrafine processing technology, devices and means (for example, pumps, valves, flow paths, sensors, etc.) for performing conventional sample preparation, chemical analysis, chemical synthesis, etc. have been miniaturized.
  • a system integrated on a chip has been developed (for example, Patent Document 1). This is also called ⁇ -TAS (Micro Total Analysis System).
  • a sample for example, urine, saliva, blood extracted from DNA subjected to DNA treatment
  • a reagent liquid In this method, the characteristics of the specimen are examined by mixing and detecting the reaction.
  • Microchip performs a photolithographic process (a method of creating a groove by etching a pattern image with a chemical) or a groove processing using laser light on a substrate made of a resin material or a glass material, and causes a reagent liquid or specimen to flow.
  • a fine flow path that can be used and a reservoir for storing reagent liquid are provided, and various patterns have been proposed (for example, Patent Document 1).
  • a small amount of reagent liquid in a fine channel and a sample are mixed at a predetermined mixing ratio to perform a reaction or the like.
  • it is necessary to accurately control the mixing ratio of the two, and for that purpose, it is important to manage the amount of the reagent liquid.
  • a reagent liquid in advance in the microchip and newly inject only the sample when performing the test.
  • the reagent liquid will evaporate, so the mixing ratio can be controlled. May be difficult.
  • Patent Document 2 discloses a microchip that prevents the reagent liquid from evaporating by sealing the outside of the reagent liquid in the flow path with an inert liquid.
  • an object of the present invention is to provide a microchip having a reagent liquid stored therein that can be stored for a long period of time.
  • a microchip stored in a packaging bag having a moisture barrier property or a gas barrier property A microfluidic channel; a reagent liquid reservoir that stores a reagent liquid for feeding the microfluidic channel and mixing it with a sample; a dummy liquid reservoir that stores a dummy liquid for evaporation; and the dummy liquid An opening connected to the reservoir,
  • microchip as described in 1 above, further comprising an inlet for injecting the reagent liquid into the reagent liquid reservoir.
  • microchip housed in the packaging bag, wherein the injection port is closed by a sealing member, and the opening is not closed. Microchip.
  • the present invention it is possible to provide a microchip that can be stored for a long period of time and stores a reagent liquid therein.
  • FIG. 2A is a top view of the microchip 100
  • FIG. 2B is a side view of the microchip 100
  • FIG. 1 is a schematic diagram showing an internal structure of a microchip 100.
  • FIG. It is a perspective view of the microchip 100 accommodated in the packaging bag 5 in this embodiment.
  • FIG. 5A is a top view of the microchip 100 according to the second embodiment
  • FIG. 5B is a schematic diagram showing the internal structure of the microchip 100. It is a graph which shows transition of the evaporation amount of the reagent liquid with the elapsed days in an Example and a comparative example.
  • microchip refers to a chip in a micro total analysis system used for various applications such as synthesis and inspection, and “microchip” particularly used for inspection of biological materials.
  • the “fine channel” may refer only to a narrow channel portion excluding a structure portion that may be formed wide, but in a broad sense includes such a structure portion.
  • the fluid flowing in the communicating fine flow path is actually a liquid, and specifically, various reagent liquids, sample liquids, denaturant liquids, cleaning liquids, driving liquids, and the like are applicable.
  • the present invention can be applied to a reaction detection apparatus using a microchip regardless of the use of the microchip.
  • embodiments of the present invention will be described with reference to the drawings.
  • FIG. 1 is a schematic diagram illustrating an example of a micro analysis system.
  • FIG. 1 shows a state in which the microchip 100 according to the present embodiment is loaded on the inspection apparatus 20 that is the micro-analysis system according to the present embodiment.
  • the inspection apparatus 20 is included in a micropump unit 210 that feeds liquid in the microchip, a heating / cooling unit 230 for promoting and suppressing the reaction in the microchip, and a product liquid obtained by the reaction in the microchip.
  • a detection unit 250 that detects the target substance to be detected
  • a drive control unit 270 that drives, controls, and detects each unit in the inspection apparatus.
  • the micropump unit 210 includes a micropump 211 that performs liquid feeding, a chip connection unit 213 that connects the micropump 211 and the microchip 100, a driving liquid tank 215 that is filled with driving liquid for liquid feeding, and a driving liquid tank 215.
  • the driving liquid supply unit 217 and the like for supplying the driving liquid to the micro pump 211.
  • the driving liquid tank 215 can be removed and replaced from the driving liquid supply unit 217 for replenishment of the driving liquid.
  • the micropump 211 is formed by one or a plurality of pumps. In the case of a plurality of micropumps 211, the micropumps 211 can be driven independently or in conjunction with each other.
  • the heating / cooling unit 230 includes a cooling unit 231 configured with a Peltier element and the like, a heating unit 233 configured with a heater and the like. Of course, the heating unit may also be composed of Peltier elements.
  • the detection unit 250 includes a light emitting diode (LED) 251 and a light receiving element (PD) 253, and optically detects a target substance contained in a product solution obtained by a reaction in the microchip.
  • LED light emitting diode
  • PD light receiving element
  • the microchip 100 and the micropump 211 are connected and communicated with each other via a chip connection unit 213, and when the micropump 211 is driven, various reagent liquids and specimens stored in a plurality of storage units in the microchip 100 are transferred. Then, the liquid is fed through the air by the driving liquid flowing into the microchip 100 from the micropump 211 via the chip connection portion 213.
  • FIG. 2A is a top view of the microchip 100
  • FIG. 2B is a side view of the microchip 100.
  • the microchip 100 includes a groove forming substrate 108 and a covering substrate 109 that covers the groove forming substrate 108.
  • the groove forming substrate 108 is formed with respective structural parts such as a reagent liquid storage part, which will be described later, and fine flow channels r1 and r2 (see FIG. 3) for communicating these structural parts.
  • the width and height of the fine channels r1 and r2 are about several ⁇ m to several hundred ⁇ m.
  • the size of the microchip 100 is usually about several tens mm in length and width and about several mm in height.
  • the microchip 100 is configured by bringing the covering substrate 109 into close contact with the groove forming substrate 108 and covering these structural portions and the fine flow path.
  • at least to-be-detected part needs to use the light-transmitting material with respect to detection light among said structure parts.
  • the microchip 100 is usually manufactured by appropriately combining one or more molding materials.
  • the molding material for the microchip 100 include plastic resins, various inorganic glasses, silicon, ceramics, and metals.
  • plastic resins plastic resins
  • the substrate for forming and processing the flow path such as the groove forming substrate 108, the flow path is not easily deformed due to water absorption, and a hydrophobic and water-repellent plastic is used so that a small amount of sample liquid can be fed without loss in the middle. preferable.
  • polystyrene examples include resins such as polystyrene, polyethylene, polypropylene, polyethylene terephthalate, polyethylene naphthalate, polyethylene vinyl alcohol, polycarbonate, polymethylpentene, fluorocarbon, and saturated cyclic polyolefin.
  • resins such as polystyrene, polyethylene, polypropylene, polyethylene terephthalate, polyethylene naphthalate, polyethylene vinyl alcohol, polycarbonate, polymethylpentene, fluorocarbon, and saturated cyclic polyolefin.
  • polystyrene is preferable as a material for forming the groove forming substrate 108 because it is excellent in transparency, mechanical properties, and moldability, and can be finely processed.
  • the coated substrate 109 is made of a flexible material such as polyolefin, and is provided with openings (holes) that connect the internal structures and the outside air, or the fine flow path and the outside air.
  • openings include an injection port for injecting a reagent liquid or a specimen sample, a connection port connected to a micropump via a chip connection portion, and various holes opened to the outside air.
  • polyolefins include polypropylene, polycarbonate, polystyrene, polyethylene, and cycloolefin polymers.
  • FIG. 3 is a schematic diagram showing the internal structure of the microchip 100 and shows a state where the covering substrate 109 is removed.
  • 133a and 133b are reagent liquid storage units for storing reagent liquids
  • 137 is a sample storage unit for storing sample samples.
  • constituent elements are generically indicated by reference numerals with alphabetic suffixes omitted, and individual constituent elements are indicated by reference numerals with suffixes.
  • an inlet i1 for injecting a reagent liquid and an inlet i3 for injecting a specimen sample are provided beside each storage unit.
  • connection ports 132a and 132b opened from one surface of the microchip 100 to the outside are provided on the upstream side in the liquid feeding direction of the storage unit.
  • the microchip 100 is connected to the micropump 211 through the connection ports 132 a and 132 b and the chip connection part 213 so as to be connected to the micropump 211.
  • a reaction unit 139 that mixes and reacts the reagent liquid from the reagent liquid storage unit 133 and the liquid from the sample storage unit 137 is provided downstream of the reagent liquid storage unit 133 and the sample storage unit 137.
  • a detected part 148 is provided downstream of the reaction part 139, and a waste liquid part 60 is provided further downstream.
  • the detection unit 250 detects the reaction of the detected unit 148.
  • the reagent liquid stored in the reagent liquid storage part 133 is driven via air by the driving liquid sent from the micro pump 211 communicating with the connection port 132a (flowed) and flows into the reaction part 139.
  • the sample stored in the specimen storage unit 137 is driven by the driving liquid sent from the separate micro pump 211 communicating with the connection port 132b and flows into the reaction unit 139.
  • the reaction part 139 the reagent liquid sent from the reagent liquid storage part 133 and the sample sent from the sample storage part 137 are mixed.
  • the reagent liquid and the sample mixed in the reaction unit 139 are heated by the heating unit 233 provided in the inspection apparatus 20 to start the reaction.
  • the liquid after the reaction is sent to the detected part 148.
  • the target substance is detected by, for example, an optical detection method.
  • the liquid detected by the detected part 148 is sent to the waste liquid part 60.
  • the present invention is not limited to this, and the pressurized air is directly connected by the syringe pump.
  • the reagent liquid or the like may be fed by being fed into the port 132.
  • the dummy liquid storage unit 150 stores a dummy liquid.
  • the dummy liquid is not used for inspection. If the reagent liquid is an aqueous solution, the dummy liquid uses an aqueous solution or pure water. If the reagent liquid is an alcohol solution, the dummy liquid also uses an alcohol solution or alcohol. By doing so, the dummy liquid or its solvent is shared with the reagent liquid solvent. That is, the evaporation component from the dummy liquid is common with at least a part of the evaporation component from the reagent liquid, and therefore the evaporation component from the dummy liquid (or its solvent) that more actively evaporates causes the inside of the packaging bag 5 to be inside. Can be prevented from evaporating from the reagent liquid using the same solvent.
  • dummy liquids not only one type of dummy liquid but also different types of dummy liquids may be stored in the plurality of dummy liquid storage units 150.
  • reagent liquids using different types of solvents are stored in the reagent liquid storage units 133a and 133b, it is preferable to use dummy liquids corresponding to the plurality of types of solvents.
  • the dummy liquid is injected from the opening i2 into the dummy liquid storage unit 150, and the opening i2 and the dummy liquid storage unit 150 are connected by the fine flow path r1.
  • the dummy liquid storage unit 150 is connected to a fine channel r2 having a different path from the fine channel r1 to which the reagent liquid storage unit 133 storing the reagent liquid is connected.
  • FIG. 4 is a perspective view of the microchip 100 housed in the packaging bag according to the present embodiment.
  • Reference numeral 5 denotes a packaging bag in which the microchip 100 is accommodated in an inside sealed with an adhesive 51.
  • the packaging bag 5 is made of a flexible packaging material having gas barrier properties or moisture barrier properties.
  • the “packaging bag having moisture barrier property or gas barrier property” of the present invention refers to a packaging bag formed of a packaging material having a performance higher than a moisture permeability of 10.0 g / m 2 / day.
  • the moisture permeability is preferably 0.5 g / m2 / day or less, and more preferably 0.05 g / m2 / day or less.
  • the moisture permeability is measured under the conditions of 40 ° C. and 90% RH according to the method described in JIS-Z-0208. The lower the numerical value of moisture permeability, the better because the gas in which the liquid inside has evaporated does not leak to the outside of the packaging bag.
  • the microchip 100 in which the dummy liquid of the same system as the reagent liquid is stored is accommodated in the packaging bag 5 having a low value of moisture permeability of 0.05 g / m 2 / day.
  • the dummy liquid also evaporates along with the reagent liquid, so that the inside of the packaging bag 5 can be quickly brought into a saturated state of the evaporated gas (saturated water vapor state if water). Thereby, evaporation derived from the reagent liquid can be suppressed.
  • the dummy liquid can be stored in a larger amount than the reagent liquid, and the dummy liquid storage portion Since the flow path 150 communicates with the plurality of openings i2, the evaporation of the dummy liquid is more dominant than the evaporation of the reagent liquid, so that the evaporation of the reagent liquid can be further suppressed.
  • the dummy liquid storage part 150 and the opening part i2 of the dummy liquid are connected by the fine flow path r2, excessive evaporation can be prevented and, in turn, the occurrence of condensation within the packaging bag 5 can be suppressed. it can. Further, since the liquid is connected to the outside via the fine channel r2, the liquid dummy liquid is difficult to move in the fine channel r2 due to its surface tension. As a result, even when the microchip 100 is tilted during transportation or the like, the liquid dummy liquid can be prevented from leaking outside the microchip 100.
  • the injection port i1 of the microchip 100 Prior to being housed in the packaging bag 5, the injection port i1 of the microchip 100 is closed with a sealing member such as a thermoplastic resin, and the opening i2 is not closed. .
  • the microchip 100 in such a state is stored in the packaging bag 5.
  • the reagent liquid in the reagent liquid storage unit 133 does not come into direct contact with the outside air. Therefore, the evaporation of the reagent liquid to the outside of the microchip 100 (inside the packaging bag 5) occurs on the groove forming substrate 108. Only the amount that evaporates through the substrate.
  • the packaging bag 5 is made of a material having a moisture barrier property or a gas barrier property, the reagent liquid is difficult to evaporate after becoming saturated, and thus the evaporation of the reagent liquid can be further suppressed. Thereby, the amount of the reagent liquid can be accurately maintained over a long period of time, and a long-term storage of the microchip in which the reagent liquid is stored can be realized.
  • FIG. 5A is a top view of the microchip 100 according to the second embodiment
  • FIG. 5B is a schematic diagram showing the internal structure of the microchip 100. 2 correspond to FIG. 2A and FIG. 3, respectively, and components having the same functions as those of the microchip 100 in the embodiment shown in FIG. 2, FIG.
  • the microchip 100 in the second embodiment is not provided with the injection ports i1 and i3. Instead of the opening i2 for evaporating the dummy liquid, a line of openings g is newly provided.
  • the dummy liquid is injected into the dummy liquid reservoir 150 and the reagent liquid is injected into the reagent liquid reservoir 133.
  • the injection port can be omitted and there is no need to seal with a sealing member.
  • injection of the specimen sample into the specimen reservoir 137 is performed, for example, by inserting a syringe needle into the coated substrate 109 above the specimen reservoir 137.
  • the opening g is provided above the fine channel r2 adjacent to the dummy liquid reservoir 150, and the opening g and the dummy liquid reservoir 150 are communicated with each other via the fine channel r1.
  • the dummy liquid is evaporated from the opening g.
  • FIG. 6 is a graph showing the transition of the evaporation amount of the reagent liquid with the elapsed days in the example and the comparative example.
  • evaporation occurs initially but tends to be saturated.
  • the reduction in reagent liquid due to evaporation at saturation is approximately 1%.
  • the comparative example it can be seen that the evaporation rate of the reagent liquid is high, and no saturation tendency is observed, and evaporation continues at a constant rate.
  • the decrease in reagent liquid due to evaporation is about 6% when 120 days have passed.
  • the storage period is longer than 120 days, since the saturation tendency is not shown in the embodiment, the difference further increases.

Landscapes

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

Abstract

Provided is a microchip which can internally store a liquid reagent for a long period of time. The microchip is therefore provided with a micro-channel (r1), a liquid reagent reservoir (133) which stores a liquid reagent that is transferred through the micro-channel (r1) and mixed with a sample, and a dummy liquid reservoir (150) which stores a dummy liquid for evaporation. The microchip is stored in a packaging bag having moisture barrier properties or gas barrier properties.

Description

マイクロチップMicrochip
　本願発明は内部に試薬液体を貯留したマイクロチップに関する。 The present invention relates to a microchip having a reagent liquid stored therein.
　近年、マイクロマシン技術および超微細加工技術を駆使することにより、従来の試料調製、化学分析、化学合成などを行うための装置、手段（例えばポンプ、バルブ、流路、センサーなど）を微細化して１チップ上に集積化したシステムが開発されている（例えば特許文献１）。これは、μ－ＴＡＳ（Ｍｉｃｒｏ　Ｔｏｔａｌ　Ａｎａｌｙｓｉｓ　Ｓｙｓｔｅｍ）とも呼ばれ、マイクロチップといわれる部材中で、検体（例えば、検査を受ける被験者の尿、唾液、血液をＤＮＡ処理した抽出溶液など）と試薬液体を混合させ、その反応を検出することにより検体の特性を調べる方法である。 In recent years, by making full use of micromachine technology and ultrafine processing technology, devices and means (for example, pumps, valves, flow paths, sensors, etc.) for performing conventional sample preparation, chemical analysis, chemical synthesis, etc. have been miniaturized. A system integrated on a chip has been developed (for example, Patent Document 1). This is also called μ-TAS (Micro Total Analysis System). In a member called a microchip, a sample (for example, urine, saliva, blood extracted from DNA subjected to DNA treatment) and a reagent liquid are collected. In this method, the characteristics of the specimen are examined by mixing and detecting the reaction.
　マイクロチップは、樹脂材料やガラス材料からなる基体に、フォトリソプロセス（パターン像を薬品によってエッチングして溝を作成する方法）や、レーザ光を利用して溝加工を行い、試薬液体や検体を流すことができる微細な流路と試薬液体を蓄える貯留部を設けており、さまざまなパターンが提案されている（例えば特許文献１）。 Microchip performs a photolithographic process (a method of creating a groove by etching a pattern image with a chemical) or a groove processing using laser light on a substrate made of a resin material or a glass material, and causes a reagent liquid or specimen to flow. A fine flow path that can be used and a reservoir for storing reagent liquid are provided, and various patterns have been proposed (for example, Patent Document 1).
　マイクロチップにおいては、微細流路内の微量の試薬液体と検体と所定の混合比で混合させて反応等を行う。反応の際には両者の混合比を精度良くコントロールすることが必要であり、そのためには試薬液体の量を管理することが重要である。 In a microchip, a small amount of reagent liquid in a fine channel and a sample are mixed at a predetermined mixing ratio to perform a reaction or the like. In the reaction, it is necessary to accurately control the mixing ratio of the two, and for that purpose, it is important to manage the amount of the reagent liquid.
　また検査を円滑に行うためにはマイクロチップ内にはあらかじめ試薬液体を貯留させておいて、検査を行う際に検体のみをあらたに注入することが好ましい。しかし、このような場合には、試薬液体をマイクロチップ内に貯留させた状態で、すぐに検査を行わず、長期に渡って保管すると、試薬液体が蒸発してしまうために混合比のコントロールが困難となる虞がある。 Also, in order to perform the test smoothly, it is preferable to store a reagent liquid in advance in the microchip and newly inject only the sample when performing the test. However, in such a case, if the reagent liquid is stored in the microchip and not immediately inspected and stored for a long period of time, the reagent liquid will evaporate, so the mixing ratio can be controlled. May be difficult.
　このような問題に対して特許文献２においては、流路内の試薬液体の外側を不活性の液体でシールすることにより試薬液体の蒸発を防ぐマイクロチップが開示されている。 For such a problem, Patent Document 2 discloses a microchip that prevents the reagent liquid from evaporating by sealing the outside of the reagent liquid in the flow path with an inert liquid.
特開２００４－２８５８９号公報JP 2004-28589 A 特開２００５－２７４１９９号公報JP 2005-274199 A
　しかし、特許文献２に開示されたマイクロチップでは、マイクロチップの外気と触れている液体は蒸発し続けるため、シール液体は最終的には消失してしまうことになり、長期間の保管には適さない。またシール液体と試薬液体とは相互に不活性な液体としなくてはならず、シール液体と試薬液体との組み合わせに制約が生じるおそれがある。 However, in the microchip disclosed in Patent Document 2, since the liquid in contact with the outside air of the microchip continues to evaporate, the sealing liquid will eventually disappear, which is suitable for long-term storage. Absent. Further, the seal liquid and the reagent liquid must be inert to each other, and there is a possibility that the combination of the seal liquid and the reagent liquid may be restricted.
　本願発明は上記問題に鑑み、長期に渡って保管可能な、内部に試薬液体を貯留したマイクロチップを提供することを目的とする。 In view of the above problems, an object of the present invention is to provide a microchip having a reagent liquid stored therein that can be stored for a long period of time.
　１．水分バリア性又はガスバリア性のある包装袋に収納されたマイクロチップであって、
微細流路と、前記微細流路を送液させて検体と混合させるための試薬液体が貯留された試薬液体貯留部と、蒸発用のダミー液体が貯留されたダミー液体貯留部と、前記ダミー液体貯留部と接続する開口部とを備え、
前記ダミー液体からの蒸発成分は、前記試薬液体からの蒸発成分の少なくとも一部と共通することを特徴とするマイクロチップ。 1. A microchip stored in a packaging bag having a moisture barrier property or a gas barrier property,
A microfluidic channel; a reagent liquid reservoir that stores a reagent liquid for feeding the microfluidic channel and mixing it with a sample; a dummy liquid reservoir that stores a dummy liquid for evaporation; and the dummy liquid An opening connected to the reservoir,
The microchip according to claim 1, wherein the evaporation component from the dummy liquid is common to at least a part of the evaporation component from the reagent liquid.
　２．前記試薬液体を前記試薬液体貯留部に注入するための注入口を備えたことを特徴とする前記１に記載のマイクロチップ。 2. 2. The microchip as described in 1 above, further comprising an inlet for injecting the reagent liquid into the reagent liquid reservoir.
　３．前記ダミー液体貯留部と前記開口部とは微細流路で連結されていることを特徴とする前記１又は２に記載のマイクロチップ。 3. 3. The microchip as described in 1 or 2 above, wherein the dummy liquid storage part and the opening part are connected by a fine channel.
　４．前記試薬液体は水溶液であり、前記蒸発用のダミー液体は水溶液又は水であることを特徴とする前記１から３のいずれかに記載のマイクロチップ。 4. 4. The microchip according to any one of 1 to 3, wherein the reagent liquid is an aqueous solution, and the dummy liquid for evaporation is an aqueous solution or water.
　５．前記試薬液体はアルコール溶液であり、前記蒸発用のダミー液体はアルコール溶液又はアルコールであることを特徴とする前記１から３のいずれかに記載のマイクロチップ。 5. 4. The microchip according to any one of 1 to 3, wherein the reagent liquid is an alcohol solution, and the evaporation dummy liquid is an alcohol solution or alcohol.
　６．前記包装袋に収納されているマイクロチップは、前記注入口を封止部材により塞がれており、前記開口部は塞がれていないことを特徴とする前記１から５のいずれかに記載のマイクロチップ。 6. 6. The microchip housed in the packaging bag, wherein the injection port is closed by a sealing member, and the opening is not closed. Microchip.
　本願発明によれば、長期に渡って保管可能な、内部に試薬液体を貯留したマイクロチップを提供することが可能となる。 According to the present invention, it is possible to provide a microchip that can be stored for a long period of time and stores a reagent liquid therein.
マイクロ分析システムの一例を示す模式図である。It is a schematic diagram which shows an example of a micro analysis system. 図２（ａ）はマイクロチップ１００の上面図、図２（ｂ）はマイクロチップ１００の側面図を示す図である。2A is a top view of the microchip 100, and FIG. 2B is a side view of the microchip 100. FIG. マイクロチップ１００の内部構造を示す模式図である。1 is a schematic diagram showing an internal structure of a microchip 100. FIG. 本実施形態における包装袋５に収納されたマイクロチップ１００の斜視図である。It is a perspective view of the microchip 100 accommodated in the packaging bag 5 in this embodiment. 図５（ａ）は第２の実施形態におけるマイクロチップ１００の上面図、図５（ｂ）は同マイクロチップ１００の内部構造を示す模式図である。FIG. 5A is a top view of the microchip 100 according to the second embodiment, and FIG. 5B is a schematic diagram showing the internal structure of the microchip 100. 実施例と比較例における、経過日数にともなう試薬液体の蒸発量の推移を示すグラフである。It is a graph which shows transition of the evaporation amount of the reagent liquid with the elapsed days in an Example and a comparative example.
　本発明を実施の形態に基づいて説明するが、本発明は該実施の形態に限られない。 The present invention will be described based on an embodiment, but the present invention is not limited to the embodiment.
　本明細書において、「マイクロチップ」は、合成や検査などさまざまな用途に用いられるマイクロ総合分析システムにおけるチップのことであるが、特に生体物質を対象とした検査に用いられるものについて「マイクロチップ」と呼ぶこともある。「微細流路」は、狭義には、広幅に形成されることもある構造部を除いた幅の狭い流路部位のみを指すこともあるが、広義には、そのような構造部を含めた一連の流路を指す。連通する微細流路内を流れる流体は、実際は液体であることが多く、具体的には、各種の試薬液、試料液、変性剤液、洗浄液、駆動液などが該当する。 In the present specification, “microchip” refers to a chip in a micro total analysis system used for various applications such as synthesis and inspection, and “microchip” particularly used for inspection of biological materials. Sometimes called. In the narrow sense, the “fine channel” may refer only to a narrow channel portion excluding a structure portion that may be formed wide, but in a broad sense includes such a structure portion. Refers to a series of flow paths. In many cases, the fluid flowing in the communicating fine flow path is actually a liquid, and specifically, various reagent liquids, sample liquids, denaturant liquids, cleaning liquids, driving liquids, and the like are applicable.
　本発明は、マイクロチップの用途にかかわらず、マイクロチップを用いた反応検出装置に適用できる。以下、図面に基づき本発明の実施形態を説明する。 The present invention can be applied to a reaction detection apparatus using a microchip regardless of the use of the microchip. Hereinafter, embodiments of the present invention will be described with reference to the drawings.
　まず、本実施形態におけるマイクロ総合分析システムについて、図１を用いて説明する。図１は、マイクロ分析システムの一例を示す模式図である。 First, the micro integrated analysis system in the present embodiment will be described with reference to FIG. FIG. 1 is a schematic diagram illustrating an example of a micro analysis system.
　図１においては、本実施形態におけるマイクロ分析システムである検査装置２０に、本実施形態におけるマイクロチップ１００を装填した状態を示している。図１において検査装置２０は、マイクロチップ内の送液を行うマイクロポンプユニット２１０、マイクロチップ内の反応を促進および抑制するための加熱冷却ユニット２３０、マイクロチップ内の反応によって得られる生成液に含まれる標的物質を検出する検出部２５０、および検査装置内の各部の駆動、制御、検出等を行う駆動制御部２７０等で構成される。 FIG. 1 shows a state in which the microchip 100 according to the present embodiment is loaded on the inspection apparatus 20 that is the micro-analysis system according to the present embodiment. In FIG. 1, the inspection apparatus 20 is included in a micropump unit 210 that feeds liquid in the microchip, a heating / cooling unit 230 for promoting and suppressing the reaction in the microchip, and a product liquid obtained by the reaction in the microchip. A detection unit 250 that detects the target substance to be detected, and a drive control unit 270 that drives, controls, and detects each unit in the inspection apparatus.
　マイクロポンプユニット２１０は、送液を行うマイクロポンプ２１１、マイクロポンプ２１１とマイクロチップ１００とを接続するチップ接続部２１３、送液のための駆動液が充填された駆動液タンク２１５および駆動液タンク２１５からマイクロポンプ２１１に駆動液を供給するための駆動液供給部２１７等で構成される。駆動液タンク２１５は、駆動液の補充のために駆動液供給部２１７から取り外して交換可能である。マイクロポンプ２１１は１個又は複数のポンプで形成されており、複数の場合は、各々独立にあるいは連動して駆動可能に構成されている。 The micropump unit 210 includes a micropump 211 that performs liquid feeding, a chip connection unit 213 that connects the micropump 211 and the microchip 100, a driving liquid tank 215 that is filled with driving liquid for liquid feeding, and a driving liquid tank 215. The driving liquid supply unit 217 and the like for supplying the driving liquid to the micro pump 211. The driving liquid tank 215 can be removed and replaced from the driving liquid supply unit 217 for replenishment of the driving liquid. The micropump 211 is formed by one or a plurality of pumps. In the case of a plurality of micropumps 211, the micropumps 211 can be driven independently or in conjunction with each other.
　加熱冷却ユニット２３０は、ペルチエ素子等で構成される冷却部２３１およびヒータ等で構成される加熱部２３３等で構成される。もちろん、加熱部もペルチエ素子で構成してもよい。検出部２５０は、発光ダイオード（ＬＥＤ）２５１および受光素子（ＰＤ）２５３等で構成され、マイクロチップ内の反応によって得られる生成液に含まれる標的物質を光学的に検出する。 The heating / cooling unit 230 includes a cooling unit 231 configured with a Peltier element and the like, a heating unit 233 configured with a heater and the like. Of course, the heating unit may also be composed of Peltier elements. The detection unit 250 includes a light emitting diode (LED) 251 and a light receiving element (PD) 253, and optically detects a target substance contained in a product solution obtained by a reaction in the microchip.
　マイクロチップ１００とマイクロポンプ２１１とはチップ接続部２１３で接続されて連通され、マイクロポンプ２１１が駆動されることにより、マイクロチップ１００内の複数の収容部に収容されている各種試薬液体や検体が、マイクロポンプ２１１からチップ接続部２１３を介してマイクロチップ１００に流入する駆動液により空気を介して送液される。 The microchip 100 and the micropump 211 are connected and communicated with each other via a chip connection unit 213, and when the micropump 211 is driven, various reagent liquids and specimens stored in a plurality of storage units in the microchip 100 are transferred. Then, the liquid is fed through the air by the driving liquid flowing into the microchip 100 from the micropump 211 via the chip connection portion 213.
　図２（ａ）はマイクロチップ１００の上面図、図２（ｂ）はマイクロチップ１００の側面図を示す図である。図２（ｂ）に示すようにマイクロチップ１００は溝形成基板１０８と、溝形成基板１０８を覆う被覆基板１０９から構成されている。溝形成基板１０８には、後述の試薬液体貯留部等の各構造部と、これらの構造部を連通させる微細流路ｒ１、ｒ２（図３参照）が形成されている。微細流路ｒ１、ｒ２の幅および高さとしては数μｍ～数百μｍ程度である。またマイクロチップ１００のサイズは、通常、縦横が数十ｍｍ、高さが数ｍｍ程度である。 2A is a top view of the microchip 100, and FIG. 2B is a side view of the microchip 100. FIG. As shown in FIG. 2B, the microchip 100 includes a groove forming substrate 108 and a covering substrate 109 that covers the groove forming substrate 108. The groove forming substrate 108 is formed with respective structural parts such as a reagent liquid storage part, which will be described later, and fine flow channels r1 and r2 (see FIG. 3) for communicating these structural parts. The width and height of the fine channels r1 and r2 are about several μm to several hundred μm. The size of the microchip 100 is usually about several tens mm in length and width and about several mm in height.
　溝形成基板１０８に被覆基板１０９を密着させてこれらの構造部および微細流路を覆うことによりマイクロチップ１００が構成される。なお、マイクロチップ１００内における反応を光学的に検出する構成とした場合には上記の構造部のうち少なくとも被検出部は検出光に対して光透過性の材料を用いる必要がある。 The microchip 100 is configured by bringing the covering substrate 109 into close contact with the groove forming substrate 108 and covering these structural portions and the fine flow path. In addition, when it is set as the structure which detects the reaction in the microchip 100 optically, at least to-be-detected part needs to use the light-transmitting material with respect to detection light among said structure parts.
　また、マイクロチップ１００は、通常は１以上の成形材料を適宜に組み合わせて作製される。マイクロチップ１００の成形材料としては、例えば、プラスチック樹脂、各種の無機ガラス、シリコン、セラミックス、金属などが挙げられる。中でも、多数の測定検体、とりわけ汚染、感染のリスクのある臨床検体を対象とするチップに対しては、ディスポーサブルであることが望まれ、更に多用途対応性、量産性などを具えることが望ましい点から、マイクロチップ１００の成形材料としてプラスチック樹脂を用いることが好ましい。溝形成基板１０８など流路を形成加工する基板では、吸水による流路の変形などが起こりにくく、微量の検体液が途中でロスすることなく送液されるように疎水性、撥水性のプラスチックが好ましい。このような材質には、ポリスチレン、ポリエチレン、ポリプロピレン、ポリエチレンテレフタレート、ポリエチレンナフタレート、ポリエチレンビニルアルコール、ポリカーボネート、ポリメチルペンテン、フルオロカーボン、飽和環状ポリオレフィンなどの樹脂が例示される。中でもポリスチレンは、透明性、機械的特性および成型性に優れて微細加工がしやすく、溝形成基板１０８の形成材料として好ましい。 Further, the microchip 100 is usually manufactured by appropriately combining one or more molding materials. Examples of the molding material for the microchip 100 include plastic resins, various inorganic glasses, silicon, ceramics, and metals. Above all, it is desirable to be disposable for chips that target a large number of samples to be measured, especially clinical samples that are at risk of contamination and infection, and it is also desirable to have versatility and mass productivity. From the viewpoint, it is preferable to use a plastic resin as a molding material of the microchip 100. In the substrate for forming and processing the flow path such as the groove forming substrate 108, the flow path is not easily deformed due to water absorption, and a hydrophobic and water-repellent plastic is used so that a small amount of sample liquid can be fed without loss in the middle. preferable. Examples of such materials include resins such as polystyrene, polyethylene, polypropylene, polyethylene terephthalate, polyethylene naphthalate, polyethylene vinyl alcohol, polycarbonate, polymethylpentene, fluorocarbon, and saturated cyclic polyolefin. Among them, polystyrene is preferable as a material for forming the groove forming substrate 108 because it is excellent in transparency, mechanical properties, and moldability, and can be finely processed.
　被覆基板１０９は、ポリオレフィン類等の可撓性材料から構成されており、内部の各構造部と外気、或いは微細流路と外気とを結ぶ開口（孔）が設けられている。開口には、例えば試薬液体や検体試料を注入する注入口、チップ接続部を介してマイクロポンプに接続する接続口、その他に外気へ開放される各種の孔等を挙げることができる。ポリオレフィン類としては例えば、ポリプロピレン、ポリカーボネート、ポリスチレン、ポリエチレン、シクロオレフィンポリマーがある。 The coated substrate 109 is made of a flexible material such as polyolefin, and is provided with openings (holes) that connect the internal structures and the outside air, or the fine flow path and the outside air. Examples of the opening include an injection port for injecting a reagent liquid or a specimen sample, a connection port connected to a micropump via a chip connection portion, and various holes opened to the outside air. Examples of polyolefins include polypropylene, polycarbonate, polystyrene, polyethylene, and cycloolefin polymers.
　次に、第１の実施形態におけるマイクロチップ１００の内部構成について、図３を用いて説明する。図３は、マイクロチップ１００の内部構造を示す模式図であり、被覆基板１０９を取り外した状態を示している。１３３ａ、１３３ｂは試薬液体を収容する試薬液体貯留部であり、１３７は検体試料を収容する検体貯留部である。 Next, the internal configuration of the microchip 100 according to the first embodiment will be described with reference to FIG. FIG. 3 is a schematic diagram showing the internal structure of the microchip 100 and shows a state where the covering substrate 109 is removed. 133a and 133b are reagent liquid storage units for storing reagent liquids, and 137 is a sample storage unit for storing sample samples.
　なお本願明細書においては構成要素を総称する場合にはアルファベットの添え字を省略した参照符号で示し、個別の構成要素を指す場合には添え字を付した参照符号で示す。 In the specification of the present application, constituent elements are generically indicated by reference numerals with alphabetic suffixes omitted, and individual constituent elements are indicated by reference numerals with suffixes.
　またそれぞれの貯留部の脇には、試薬液体を注入する注入口ｉ１、検体試料を注入する注入口ｉ３が設けられている。また貯留部の送液方向上流側には、マイクロチップ１００の一方の面から外部へ開放された接続口１３２ａ、１３２ｂが設けられている。マイクロチップ１００はこれらの接続口１３２ａ、１３２ｂとチップ接続部２１３とを介してマイクロポンプ２１１に重ね合わせて接続してマイクロポンプ２１１に連通される。 Further, an inlet i1 for injecting a reagent liquid and an inlet i3 for injecting a specimen sample are provided beside each storage unit. Further, connection ports 132a and 132b opened from one surface of the microchip 100 to the outside are provided on the upstream side in the liquid feeding direction of the storage unit. The microchip 100 is connected to the micropump 211 through the connection ports 132 a and 132 b and the chip connection part 213 so as to be connected to the micropump 211.
　試薬液体貯留部１３３および検体貯留部１３７の下流には、試薬液体貯留部１３３からの試薬液体と検体貯留部１３７からの液体とが混合され反応する反応部１３９が設けられている。 A reaction unit 139 that mixes and reacts the reagent liquid from the reagent liquid storage unit 133 and the liquid from the sample storage unit 137 is provided downstream of the reagent liquid storage unit 133 and the sample storage unit 137.
　反応部１３９の下流には、被検出部１４８が設けられ、更に下流には廃液部６０が設けられている。前述の検出部２５０により被検出部１４８の反応を検出する。 A detected part 148 is provided downstream of the reaction part 139, and a waste liquid part 60 is provided further downstream. The detection unit 250 detects the reaction of the detected unit 148.
　試薬液体貯留部１３３に収容された試薬液体は、接続口１３２ａに連通するマイクロポンプ２１１から送り込まれる駆動液により、空気を介して駆動され（送液され）反応部１３９へ流れ込む。一方、検体貯留部１３７に収容された試料は、接続口１３２ｂに連通する別途のマイクロポンプ２１１から送り込まれる駆動液により、駆動され反応部１３９へ流れ込む。これにより、反応部１３９において、試薬液体貯留部１３３から送り込まれた試薬液体と検体貯留部１３７から送り込まれた試料とが混合される。 The reagent liquid stored in the reagent liquid storage part 133 is driven via air by the driving liquid sent from the micro pump 211 communicating with the connection port 132a (flowed) and flows into the reaction part 139. On the other hand, the sample stored in the specimen storage unit 137 is driven by the driving liquid sent from the separate micro pump 211 communicating with the connection port 132b and flows into the reaction unit 139. Thereby, in the reaction part 139, the reagent liquid sent from the reagent liquid storage part 133 and the sample sent from the sample storage part 137 are mixed.
　反応部１３９で混合された試薬液体と試料とは、検査装置２０に設けられた加熱部２３３により加熱され反応が開始される。反応後の液は、被検出部１４８へ送液される。被検出部１４８では、例えば光学的な検出方法などによって目的物質の検出が行われる。被検出部１４８にて検出された液体は、廃液部６０に送られる。 The reagent liquid and the sample mixed in the reaction unit 139 are heated by the heating unit 233 provided in the inspection apparatus 20 to start the reaction. The liquid after the reaction is sent to the detected part 148. In the detected part 148, the target substance is detected by, for example, an optical detection method. The liquid detected by the detected part 148 is sent to the waste liquid part 60.
　なお、本実施形態においては、マイクロポンプ２１１により送られた駆動液により空気を介して試薬液体等を送液させる例について説明したが、これに限られずシリンジポンプにより直接、加圧した空気を接続口１３２に送り込むようにして試薬液体等を送液させるようにしてもよい。 In the present embodiment, the example in which the reagent liquid or the like is sent via the air by the driving liquid sent by the micropump 211 has been described. However, the present invention is not limited to this, and the pressurized air is directly connected by the syringe pump. The reagent liquid or the like may be fed by being fed into the port 132.
　［ダミー液体貯留部１５０］
　ダミー液体貯留部１５０では、ダミー液体を貯留する。ダミー液体は検査には使用しない。また試薬液体が水溶液であれば、ダミー液体は水溶液又は純水を用い、試薬液体がアルコール溶液であれば、ダミー液体もアルコール溶液又はアルコールを用いる。このようにすることによりダミー液体あるいはその溶媒が、試薬液体の溶媒と共通することになる。つまりダミー液体からの蒸発成分は、試薬液体からの蒸発成分の少なくとも一部と共通することになるので、より積極的に蒸発するダミー液体（あるいはその溶媒）からの蒸発成分により包装袋５の内部を蒸発ガスの飽和状態にすることにより、同じ溶媒を用いる試薬液体からの当該溶媒の蒸発を抑止することができる。 [Dummy liquid reservoir 150]
The dummy liquid storage unit 150 stores a dummy liquid. The dummy liquid is not used for inspection. If the reagent liquid is an aqueous solution, the dummy liquid uses an aqueous solution or pure water. If the reagent liquid is an alcohol solution, the dummy liquid also uses an alcohol solution or alcohol. By doing so, the dummy liquid or its solvent is shared with the reagent liquid solvent. That is, the evaporation component from the dummy liquid is common with at least a part of the evaporation component from the reagent liquid, and therefore the evaporation component from the dummy liquid (or its solvent) that more actively evaporates causes the inside of the packaging bag 5 to be inside. Can be prevented from evaporating from the reagent liquid using the same solvent.
　またダミー液体は１種類だけでなく、複数のダミー液体貯留部１５０に互いに異なる種類のダミー液体を貯留しておいてもよい。特に、試薬液体貯留部１３３ａ、１３３ｂにそれぞれ異なる種類の溶媒を用いた試薬液体が貯留されているような場合に、その複数種類の溶媒に対応したダミー液体を用いることが好ましい。 Further, not only one type of dummy liquid but also different types of dummy liquids may be stored in the plurality of dummy liquid storage units 150. In particular, when reagent liquids using different types of solvents are stored in the reagent liquid storage units 133a and 133b, it is preferable to use dummy liquids corresponding to the plurality of types of solvents.
　またダミー液体は開口部ｉ２からダミー液体貯留部１５０に注入され、開口部ｉ２とダミー液体貯留部１５０とは微細流路ｒ１で連結されている。ここで、ダミー液体貯留部１５０は、試薬液体が貯留している試薬液体貯留部１３３が連結する微細流路ｒ１とは異なる経路の微細流路ｒ２に連結させている。 Further, the dummy liquid is injected from the opening i2 into the dummy liquid storage unit 150, and the opening i2 and the dummy liquid storage unit 150 are connected by the fine flow path r1. Here, the dummy liquid storage unit 150 is connected to a fine channel r2 having a different path from the fine channel r1 to which the reagent liquid storage unit 133 storing the reagent liquid is connected.
　［包装袋５］
　図４は、本実施形態における包装袋に収納されたマイクロチップ１００の斜視図である。５は包装袋で、接着剤５１により密閉された内部にマイクロチップ１００を収納している。この包装袋５には、ガスバリア性あるいは水分バリア性を有する可撓性の包装材を用いている。 [Packaging bag 5]
FIG. 4 is a perspective view of the microchip 100 housed in the packaging bag according to the present embodiment. Reference numeral 5 denotes a packaging bag in which the microchip 100 is accommodated in an inside sealed with an adhesive 51. The packaging bag 5 is made of a flexible packaging material having gas barrier properties or moisture barrier properties.
　ここで本発明の「水分バリア性又はガスバリア性のある包装袋」とは、透湿度１０．０ｇ／ｍ２／ｄａｙよりも性能の高い包装材で形成された包装袋をいう。 Here, the “packaging bag having moisture barrier property or gas barrier property” of the present invention refers to a packaging bag formed of a packaging material having a performance higher than a moisture permeability of 10.0 g / m 2 / day.
　包装材としては、例えばポリエステル、ポリプロピレンを基体としてその表面にアルミを蒸着させたシートを用いることができる。透湿度としては０．５ｇ／ｍ２／ｄａｙ以下であることが好ましく、０．０５ｇ／ｍ２／ｄａｙ以下であることがさらに好ましい。なお透湿度とはＪＩＳ－Ｚ－０２０８に記載の方法に従い、条件４０℃９０％ＲＨで測定したものである。透湿度の数値が低いほど、内部の液体が蒸発したガスが包装袋の外部に漏れないので、好ましい。 As the packaging material, for example, a sheet in which aluminum is deposited on the surface of polyester or polypropylene as a base can be used. The moisture permeability is preferably 0.5 g / m2 / day or less, and more preferably 0.05 g / m2 / day or less. The moisture permeability is measured under the conditions of 40 ° C. and 90% RH according to the method described in JIS-Z-0208. The lower the numerical value of moisture permeability, the better because the gas in which the liquid inside has evaporated does not leak to the outside of the packaging bag.
　本実施形態によれば、試薬液体と同系統のダミー液体を貯留させたマイクロチップ１００を、透湿度０．０５ｇ／ｍ２／ｄａｙである透湿度の数値の低い包装袋５に収容させている。これにより試薬液体の蒸発とともにダミー液体も蒸発するので、包装袋５の内部を迅速に蒸発ガスの飽和状態（水であれば飽和水蒸気状態）にすることができる。このことにより試薬液体由来の蒸発を抑制することができる。 According to the present embodiment, the microchip 100 in which the dummy liquid of the same system as the reagent liquid is stored is accommodated in the packaging bag 5 having a low value of moisture permeability of 0.05 g / m 2 / day. As a result, the dummy liquid also evaporates along with the reagent liquid, so that the inside of the packaging bag 5 can be quickly brought into a saturated state of the evaporated gas (saturated water vapor state if water). Thereby, evaporation derived from the reagent liquid can be suppressed.
　また図３等に示すように、ダミー液体を貯留するダミー液体貯留部１５０を複数設けていることからダミー液体を試薬液体に比べて多量に貯留させることが可能なこと、および当該ダミー液体貯留部１５０が連通する流路は複数の開口部ｉ２を備えているので、ダミー液体の蒸発の方が試薬液体の蒸発に比べてより支配的となるので、試薬液体の蒸発を更に抑制できる。 Further, as shown in FIG. 3 and the like, since a plurality of dummy liquid storage portions 150 for storing the dummy liquid are provided, the dummy liquid can be stored in a larger amount than the reagent liquid, and the dummy liquid storage portion Since the flow path 150 communicates with the plurality of openings i2, the evaporation of the dummy liquid is more dominant than the evaporation of the reagent liquid, so that the evaporation of the reagent liquid can be further suppressed.
　またダミー液体のダミー液体貯留部１５０と開口部ｉ２は微細流路ｒ２で連結されているので、過剰な蒸発を防止することができ、ひいては包装袋５内部での結露の発生を抑制することができる。また微細流路ｒ２を介して外部と連結されていることから液体状態のダミー液体はその表面張力により微細流路ｒ２を移動しづらい。その結果、搬送時等においてマイクロチップ１００が傾いた場合であっても、液体状態のダミー液体がマイクロチップ１００の外部へ漏れることを防止することができる。 Moreover, since the dummy liquid storage part 150 and the opening part i2 of the dummy liquid are connected by the fine flow path r2, excessive evaporation can be prevented and, in turn, the occurrence of condensation within the packaging bag 5 can be suppressed. it can. Further, since the liquid is connected to the outside via the fine channel r2, the liquid dummy liquid is difficult to move in the fine channel r2 due to its surface tension. As a result, even when the microchip 100 is tilted during transportation or the like, the liquid dummy liquid can be prevented from leaking outside the microchip 100.
　また、包装袋５に収容するに先だって、マイクロチップ１００の注入口ｉ１を熱可塑性の樹脂等の封止部材で塞がれている状態とし、開口部ｉ２は塞がれていない状態にしている。このような状態のマイクロチップ１００を包装袋５に収納させている。このようにすることにより試薬液体貯留部１３３内の試薬液体は外気とは直接触れないため、当該試薬液体のマイクロチップ１００の外（包装袋５の内部）への蒸発は、溝形成基板１０８の基材を透過して蒸発する分のみになる。一方ダミー液体は、微細流路ｒ２等を介して直接外気（包装袋５の内部）と触れるために試薬液体に比べて蒸発量は多くなる。そして包装袋５は、水分バリア性又はガスバリア性のある材料により構成しているため飽和状態となった以降は、試薬液体は蒸発しづらくなるので、試薬液体の蒸発を更に抑制できる。これにより、長期にわたり試薬液体の量を精度よく保持することができ、内部に試薬液体を貯留したマイクロチップの長期間の保管を実現できる。 Prior to being housed in the packaging bag 5, the injection port i1 of the microchip 100 is closed with a sealing member such as a thermoplastic resin, and the opening i2 is not closed. . The microchip 100 in such a state is stored in the packaging bag 5. By doing so, the reagent liquid in the reagent liquid storage unit 133 does not come into direct contact with the outside air. Therefore, the evaporation of the reagent liquid to the outside of the microchip 100 (inside the packaging bag 5) occurs on the groove forming substrate 108. Only the amount that evaporates through the substrate. On the other hand, since the dummy liquid directly contacts the outside air (inside the packaging bag 5) through the fine channel r2 and the like, the amount of evaporation is larger than that of the reagent liquid. Since the packaging bag 5 is made of a material having a moisture barrier property or a gas barrier property, the reagent liquid is difficult to evaporate after becoming saturated, and thus the evaporation of the reagent liquid can be further suppressed. Thereby, the amount of the reagent liquid can be accurately maintained over a long period of time, and a long-term storage of the microchip in which the reagent liquid is stored can be realized.
　［第２の実施形態におけるマイクロチップ１００］
　図５に基づいて第２の実施形態におけるマイクロチップ１００について説明する。図５（ａ）は第２の実施形態におけるマイクロチップ１００の上面図、図５（ｂ）は同マイクロチップ１００の内部構造を示す模式図である。それぞれ図２（ａ）、図３に対応するものであり、図２、図３等に示した実施形態おけるマイクロチップ１００と同機能の構成部に関しては同符号を付すことにより説明に代える。 [Microchip 100 in Second Embodiment]
A microchip 100 according to the second embodiment will be described with reference to FIG. FIG. 5A is a top view of the microchip 100 according to the second embodiment, and FIG. 5B is a schematic diagram showing the internal structure of the microchip 100. 2 correspond to FIG. 2A and FIG. 3, respectively, and components having the same functions as those of the microchip 100 in the embodiment shown in FIG. 2, FIG.
　第２の実施形態におけるマイクロチップ１００は、図２乃至図４に示したマイクロチップ１００と異なり注入口ｉ１、ｉ３を設けていない。なおダミー液体を蒸発させるための開口部ｉ２に代わりに、一列状の開口部ｇをあらたに設けている。 Unlike the microchip 100 shown in FIGS. 2 to 4, the microchip 100 in the second embodiment is not provided with the injection ports i1 and i3. Instead of the opening i2 for evaporating the dummy liquid, a line of openings g is newly provided.
　図５に示すマイクロチップ１００では、溝形成基板１０８に被覆基板１０９を取り付ける前に、ダミー液体貯留部１５０にダミー液体を、試薬液体貯留部１３３には試薬液体を注入している。この状態で被覆基板１０９を取り付けることにより注入口を省略することができ封止部材により封止をする必要がないというメリットがある。なお、検査時において検体試料の検体貯留部１３７への注入は、例えば、検体貯留部１３７の上方位置の被覆基板１０９に注射針を突き刺すことにより行う。 In the microchip 100 shown in FIG. 5, before attaching the covering substrate 109 to the groove forming substrate 108, the dummy liquid is injected into the dummy liquid reservoir 150 and the reagent liquid is injected into the reagent liquid reservoir 133. By attaching the covering substrate 109 in this state, there is an advantage that the injection port can be omitted and there is no need to seal with a sealing member. At the time of examination, injection of the specimen sample into the specimen reservoir 137 is performed, for example, by inserting a syringe needle into the coated substrate 109 above the specimen reservoir 137.
　また開口部ｇは、ダミー液体貯留部１５０に隣接する微細流路ｒ２の上方に設けられており、微細流路ｒ１を介して、開口部ｇとダミー液体貯留部１５０は連通されている。当該開口部ｇからダミー液体の蒸発が行われる。 The opening g is provided above the fine channel r2 adjacent to the dummy liquid reservoir 150, and the opening g and the dummy liquid reservoir 150 are communicated with each other via the fine channel r1. The dummy liquid is evaporated from the opening g.
　次に、本願発明の実施例について説明する。実施例においては図１乃至図４に示したマイクロチップを用いた。その他の詳細な条件は以下のとおりである。 Next, examples of the present invention will be described. In the example, the microchip shown in FIGS. 1 to 4 was used. Other detailed conditions are as follows.
　［実施例の実験条件］
包装袋の内部の体積（容積）　２０ｍｌ
試薬液体の体積　　　　　　　１０μｌ
ダミー液体の体積　　　　　　１０μｌ
体積比　　　　　　　　　　　包装袋内部：試薬液体：ダミー液体＝２０００：１：１
試薬液体　　　　　　　　　　水溶液
ダミー液体　　　　　　　　　純水
包装袋　　　　　　　　　　　透湿度　０．０５ｇ／ｍ２／ｄａｙのアルミ蒸着シート
保管環境：　　　　　　　　　２～８℃
試薬液体の注入孔　　　　　　封止状態
マイクロチップ材質　　　　　ポリプロピレン（透湿度　約６．５ｇ／ｍ２／ｄａｙ）
　［比較例の実験条件］
比較例では、上記実施例と同一のマイクロチップを用いているが以下の条件で異なっている。
ダミー液体の体積　　　　　　無し（貯留させず）
　［測定方法］
所定断面積の微細流路内に配置された試薬液体の端面位置の変動を測定することにより蒸発量の測定を行った。 [Experimental conditions of Examples]
Volume (volume) inside the packaging bag 20ml
Reagent liquid volume 10 μl
Dummy liquid volume 10μl
Volume ratio Inside packaging bag: reagent liquid: dummy liquid = 2000: 1: 1
Reagent liquid Aqueous solution dummy liquid Pure water packaging bag Water vapor transmission rate 0.05g / m2 / day of aluminum deposition sheet Storage environment: 2-8 ° C
Reagent liquid injection hole Sealed state Microchip material Polypropylene (moisture permeability of about 6.5 g / m2 / day)
[Experimental conditions for comparative example]
The comparative example uses the same microchip as in the above example, but differs under the following conditions.
No dummy liquid volume (not stored)
[Measuring method]
The amount of evaporation was measured by measuring the variation in the position of the end face of the reagent liquid disposed in the fine channel having a predetermined cross-sectional area.
　［実験結果］
　図６は、実施例と比較例における、経過日数にともなう試薬液体の蒸発量の推移を示すグラフである。図６に示すように実施例においては初期的には蒸発が発生しているが飽和傾向にあることがわかる。飽和時の蒸発による試薬液体の減少はおよそ１％である。一方比較例では、試薬液体の蒸発速度が速く、かつ飽和傾向はみられず一定の速度で蒸発し続けることがわかる。同図に示す例では１２０日経過時点では蒸発による試薬液体の減少はおよそ６％である。保管期間を１２０日よりも長くした場合には実施例では飽和傾向を示さないのでその差は更に拡大することになる。 [Experimental result]
FIG. 6 is a graph showing the transition of the evaporation amount of the reagent liquid with the elapsed days in the example and the comparative example. As shown in FIG. 6, it can be seen that in the example, evaporation occurs initially but tends to be saturated. The reduction in reagent liquid due to evaporation at saturation is approximately 1%. On the other hand, in the comparative example, it can be seen that the evaporation rate of the reagent liquid is high, and no saturation tendency is observed, and evaporation continues at a constant rate. In the example shown in the figure, the decrease in reagent liquid due to evaporation is about 6% when 120 days have passed. When the storage period is longer than 120 days, since the saturation tendency is not shown in the embodiment, the difference further increases.
　２０　検査装置
　５　包装袋
　１００　マイクロチップ
　１０８　溝形成基板
　１０９　被覆基板
　１３３、１３３ａ、１３３ｂ　試薬液体貯留部
　１３７　検体貯留部
　１３９　反応部
　１５０　ダミー液体貯留部
　ｒ１、ｒ２　微細流路
　ｉ１、ｉ３　注入口
　ｉ２、ｇ　開口部
　２１１　マイクロポンプ 20 Inspection device 5 Packaging bag 100 Microchip 108 Groove forming substrate 109 Coated substrate 133, 133a, 133b Reagent liquid storage part 137 Sample storage part 139 Reaction part 150 Dummy liquid storage part r1, r2 Micro flow path i1, i3 Inlet i2, g Opening 211 Micro pump

Claims (6)

  1. 水分バリア性又はガスバリア性のある包装袋に収納されたマイクロチップであって、
    微細流路と、前記微細流路を送液させて検体と混合させるための試薬液体が貯留された試薬液体貯留部と、蒸発用のダミー液体が貯留されたダミー液体貯留部と、前記ダミー液体貯留部と接続する開口部とを備え、
    前記ダミー液体からの蒸発成分は、前記試薬液体からの蒸発成分の少なくとも一部と共通することを特徴とするマイクロチップ。     A microchip stored in a packaging bag having a moisture barrier property or a gas barrier property,
    A microfluidic channel; a reagent liquid reservoir that stores a reagent liquid for feeding the microfluidic channel and mixing it with a sample; a dummy liquid reservoir that stores a dummy liquid for evaporation; and the dummy liquid An opening connected to the reservoir,
    The microchip according to claim 1, wherein the evaporation component from the dummy liquid is common to at least a part of the evaporation component from the reagent liquid.
  2. 前記試薬液体を前記試薬液体貯留部に注入するための注入口を備えたことを特徴とする請求項１に記載のマイクロチップ。 The microchip according to claim 1, further comprising an inlet for injecting the reagent liquid into the reagent liquid reservoir.
  3. 前記ダミー液体貯留部と前記開口部とは微細流路で連結されていることを特徴とする請求項１又は２に記載のマイクロチップ。 The microchip according to claim 1, wherein the dummy liquid storage portion and the opening are connected by a fine channel.
  4. 前記試薬液体は水溶液であり、前記蒸発用のダミー液体は水溶液又は水であることを特徴とする請求項１から３のいずれかに記載のマイクロチップ。 4. The microchip according to claim 1, wherein the reagent liquid is an aqueous solution, and the dummy liquid for evaporation is an aqueous solution or water.
  5. 前記試薬液体はアルコール溶液であり、前記蒸発用のダミー液体はアルコール溶液又はアルコールであることを特徴とする請求項１から３のいずれかに記載のマイクロチップ。 4. The microchip according to claim 1, wherein the reagent liquid is an alcohol solution, and the evaporation dummy liquid is an alcohol solution or alcohol.
  6. 前記包装袋に収納されているマイクロチップは、前記注入口を封止部材により塞がれており、前記開口部は塞がれていないことを特徴とする請求項１から５のいずれかに記載のマイクロチップ。 6. The microchip housed in the packaging bag has the injection port closed by a sealing member, and the opening is not closed. Microchip.
PCT/JP2009/057573 2008-04-25 2009-04-15 Microchip WO2009131043A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2010509151A JPWO2009131043A1 (en) 2008-04-25 2009-04-15 Microchip

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2008115105 2008-04-25
JP2008-115105 2008-04-25

Publications (1)

Publication Number Publication Date
WO2009131043A1 true WO2009131043A1 (en) 2009-10-29

Family

ID=41216780

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2009/057573 WO2009131043A1 (en) 2008-04-25 2009-04-15 Microchip

Country Status (2)

Country Link
JP (1) JPWO2009131043A1 (en)
WO (1) WO2009131043A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013160648A (en) * 2012-02-06 2013-08-19 Sony Corp Microchip
JP2015142893A (en) * 2014-01-31 2015-08-06 株式会社日立製作所 System and method for providing drugs
WO2019097984A1 (en) * 2017-11-15 2019-05-23 コニカミノルタ株式会社 Inspection package

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006234590A (en) * 2005-02-25 2006-09-07 Shimadzu Corp Reaction vessel
JP2006521829A (en) * 2003-04-03 2006-09-28 フルイディグム コーポレイション Microfluidic device and method of use thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006521829A (en) * 2003-04-03 2006-09-28 フルイディグム コーポレイション Microfluidic device and method of use thereof
JP2006234590A (en) * 2005-02-25 2006-09-07 Shimadzu Corp Reaction vessel

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013160648A (en) * 2012-02-06 2013-08-19 Sony Corp Microchip
JP2015142893A (en) * 2014-01-31 2015-08-06 株式会社日立製作所 System and method for providing drugs
US10005060B2 (en) 2014-01-31 2018-06-26 Hitachi, Ltd. Drug provision system and drug provision method
WO2019097984A1 (en) * 2017-11-15 2019-05-23 コニカミノルタ株式会社 Inspection package
JPWO2019097984A1 (en) * 2017-11-15 2020-11-19 コニカミノルタ株式会社 Inspection package
JP7237008B2 (en) 2017-11-15 2023-03-10 大塚製薬株式会社 inspection package

Also Published As

Publication number Publication date
JPWO2009131043A1 (en) 2011-08-18

Similar Documents

Publication Publication Date Title
US7482585B2 (en) Testing chip and micro integrated analysis system
JP3952036B2 (en) Microfluidic device, test solution test method and test system
US7820109B2 (en) Testing chip and micro analysis system
US8133456B2 (en) Microreactor and method of liquid feeding making use of the same
US7863054B2 (en) Microfluidic system, sample analysis device, and target substance detection/measurement method
WO2009131043A1 (en) Microchip
WO2007055151A1 (en) Microreactor and microanalysis system
JP2008128869A (en) Microchip inspection system and program used for the microchip inspection system
JP5177533B2 (en) Microchip
JP2006292472A (en) Micro comprehensive analysis system
JP5182099B2 (en) Microchip and microchip inspection system
JP2010057403A (en) Reaction vessel plate and method for reaction treatment
JP2010025854A (en) Micro inspection chip
JP2009109459A (en) Pipette chip, inspection system, pipette, and filling apparatus
JP2009115732A (en) Micro-inspection chip, method for micro-inspection chip to determine quantity of a liquid, and inspection method
JP2010008145A (en) Microinspection chip, quantitative liquid sending method of microinspection chip and inspection apparatus
US9945773B2 (en) Flow cell and liquid feed system
JP2009281954A (en) Reaction vessel plate and reaction processing method
WO2009113487A1 (en) Micro inspection chip and method of dividing liquid for micro inspection chip
JP2009019890A (en) Micro inspection chip and inspection device
JP2009019892A (en) Micro inspection chip and inspection device
JP2010025621A (en) Micro inspection chip, and liquid mixing sending method of micro inspection chip
WO2020251526A1 (en) Microfluidic detection unit and fluid detection method
JP2006284451A (en) Micro total analysis system for analyzing target material in specimen
JP2009058396A (en) Reaction container plate

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09735344

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2010509151

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 09735344

Country of ref document: EP

Kind code of ref document: A1