JPWO2009113487A1 - Micro inspection chip and liquid dividing method of micro inspection chip - Google Patents

Micro inspection chip and liquid dividing method of micro inspection chip Download PDF

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JPWO2009113487A1
JPWO2009113487A1 JP2010502804A JP2010502804A JPWO2009113487A1 JP WO2009113487 A1 JPWO2009113487 A1 JP WO2009113487A1 JP 2010502804 A JP2010502804 A JP 2010502804A JP 2010502804 A JP2010502804 A JP 2010502804A JP WO2009113487 A1 JPWO2009113487 A1 JP WO2009113487A1
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山東 康博
康博 山東
孝裕 毛利
孝裕 毛利
東野 楠
楠 東野
中島 彰久
彰久 中島
洋一 青木
洋一 青木
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Konica Minolta Medical and Graphic Inc
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502715Containers 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 interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/04Closures and closing means
    • B01L2300/041Connecting closures to device or container
    • B01L2300/042Caps; Plugs
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/04Closures and closing means
    • B01L2300/041Connecting closures to device or container
    • B01L2300/043Hinged closures
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867Multiple inlets and one sample wells, e.g. mixing, dilution
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087Multiple sequential chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/18Means for temperature control
    • B01L2300/1805Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1822Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00Heating or cooling apparatus; Heat insulating devices
    • B01L7/52Heating 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
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027General features of the devices
    • G01N2035/1032Dilution or aliquotting

Abstract

液体注入口に設けられた液溜り部に貯留された液体を、液溜り部に設けられた複数の連結口を介して、あるいは直接に複数の送液流路に流し込むことで液体を複数に分割することができる。また、液体注入口を封止する蓋に設けられた突起部で複数の連結口を封止することで、複数の送液流路間の連通を阻止できる。それによって、微量の液体を簡単な操作で精度よく複数の送液流路に分割して注入することができ、分割して注入した後に安定して送液することのできるマイクロ検査チップおよびマイクロチップの液体分割方法を提供することができる。Divide the liquid into multiple parts by flowing the liquid stored in the liquid reservoir provided at the liquid inlet through the multiple connection ports provided in the liquid reservoir or directly into the multiple liquid supply channels. can do. Further, by sealing the plurality of connection ports with the protrusions provided on the lid that seals the liquid injection port, communication between the plurality of liquid supply channels can be prevented. Thereby, a micro inspection chip and a microchip that can divide and inject a small amount of liquid into a plurality of liquid supply flow paths with a simple operation with high accuracy and can stably supply liquid after divided injection. The liquid dividing method can be provided.

Description

本発明は、マイクロ検査チップおよびマイクロ検査チップの液体分割方法に関し、特に、遺伝子増幅反応、抗原抗体反応などによる生体物質の検査・分析、その他の化学物質の検査・分析、有機合成等による目的化合物の化学合成などに用いられるマイクロ検査チップおよびマイクロ検査チップの液体分割方法に関する。   The present invention relates to a microinspection chip and a method for dividing a liquid into a microinspection chip, and in particular, a target compound by inspecting / analyzing biological substances by gene amplification reaction, antigen-antibody reaction, etc., inspecting / analyzing other chemical substances, organic synthesis The present invention relates to a micro inspection chip used for chemical synthesis of the liquid and a liquid dividing method of the micro inspection chip.

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分析用チップ(以下、マイクロ検査チップと言う)が開発されている(例えば、特許文献1参照)。   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. An analysis chip (hereinafter referred to as a micro inspection chip) integrated on a chip has been developed (see, for example, Patent Document 1).

これは、μ−TAS(Micro Total Analysis System)、バイオリアクタ、ラブ・オン・チップ(Lab−on−chips)、バイオチップとも呼ばれ、医療検査・診断分野、環境測定分野、農産製造分野でその応用が期待されている。特に、遺伝子検査に見られるように煩雑な工程、熟練した手技、機器類の操作が必要とされる場合には、自動化、高速化および簡便化に優れたマイクロ検査チップは、コスト、必要試料量、所要時間のみならず、時間および場所を選ばない分析を可能とするので、その恩恵は多大と言える。   This is also called μ-TAS (Micro Total Analysis System), bioreactor, Lab-on-chip, biochip, and it is used in the medical examination / diagnosis field, environmental measurement field, and agricultural production field. Application is expected. In particular, when complicated processes such as those found in genetic testing, skilled techniques, and operation of equipment are required, micro test chips that excel in automation, speed-up, and simplification are cost-effective and require sample volume. Because it enables analysis not only for the required time but also for any time and place, the benefits are great.

本出願人は、試薬などを封入したマイクロ検査チップに血液などの検体を注入し、マイクロ検査チップの微細流路にマイクロポンプで駆動液を注入することで、検体などを移動させて順次反応させ、結果を測定することができる反応検出装置を提案している(例えば、特許文献2参照)。   The present applicant injects a specimen such as blood into a micro test chip enclosing a reagent, etc., and injects a driving liquid with a micro pump into the micro flow path of the micro test chip, thereby moving the specimen and reacting sequentially. Have proposed a reaction detection device capable of measuring the results (see, for example, Patent Document 2).

上述したようなマイクロ検査チップでは、検査に用いられる血液等の検体や、検査のための試薬等の液体を、検査項目に従って、複数に分割してマイクロ検査チップに設けられた注入口からマイクロ検査チップ内に注入する作業が必要となる。このようなマイクロ検査チップへの検体の注入は、検査担当者が、スポイトやピペットなどを用いて、検体をマイクロ検査チップの注入口に注入して行っていた。
特開2004−28589号公報 特開2006−149379号公報
In the micro test chip as described above, a sample such as blood used for the test or a liquid such as a reagent for the test is divided into a plurality according to the test item and micro test is performed from the injection port provided in the micro test chip. It is necessary to inject into the chip. Injecting a specimen into such a micro test chip has been performed by a person in charge of the test using a dropper or pipette to inject the sample into the injection port of the micro test chip.
JP 2004-28589 A JP 2006-149379 A

一般的な遺伝子診断においては、単項目の診断であっても、試薬のコンディションや検体に含まれる阻害物質が診断結果に影響する可能性があるため、検体等の液体は、マイクロ検査チップ上の複数の流路へ微量ずつ取り分けて、リファレンス反応との比較で診断の信頼性を確保する方法が多く用いられる。そのためには、検体等の液体を複数に分割する必要がある。   In general genetic diagnosis, even in the case of single item diagnosis, the condition of the reagent and the inhibitor contained in the sample may affect the diagnosis result. A method is often used in which a minute amount is divided into a plurality of flow paths and the reliability of diagnosis is ensured by comparison with a reference reaction. For this purpose, it is necessary to divide a liquid such as a specimen into a plurality of parts.

例えば、図6(a)に示すように、1箇所の注入口113から液体貯留部111に注入された液体を、マイクロポンプとの接続口117から注入される駆動液によって下流に送液し、分割流路115で複数に分割(ここでは2分割)する方法が考えられる。   For example, as shown in FIG. 6A, the liquid injected into the liquid reservoir 111 from one injection port 113 is sent downstream by the driving liquid injected from the connection port 117 with the micropump, A method of dividing into a plurality of division channels 115 (here, division into two) is conceivable.

しかしながら、この場合、分割された液体が送液される先の流路115aと流路115bとが分割流路115で連通しているために、送液の際のマイクロポンプの力などが相互に影響し合い、安定な送液ができなかったり、分割時の計量精度が低下したりする問題がある。さらに多項目の診断の場合、液体をより多数に分割する必要があるので、より一層複雑な分割および連通のある流路が必要になると考えられ、マイクロ検査チップ100が大型化し、本来の小型、迅速で高精度であるμ−TASのメリットが活かせなくなってしまう。   However, in this case, since the flow path 115a and the flow path 115b to which the divided liquid is fed are communicated with each other through the divided flow path 115, the force of the micropumps at the time of liquid feeding is mutually There is a problem in that stable liquid feeding cannot be performed and measurement accuracy at the time of division is reduced. Further, in the case of multi-item diagnosis, since it is necessary to divide the liquid into a larger number, it is considered that a more complicated division and a flow path with communication are necessary, and the micro inspection chip 100 is enlarged, and the original small size, The merit of μ-TAS, which is quick and highly accurate, cannot be utilized.

また、例えば図6(b)に示すように、検査担当者が手動のピペットなどで、液体を複数(例えば2カ所)の注入口(例えば113aおよび113b)からそれぞれの液体貯留部(例えば111aおよび111b)に注入する方法も考えられる。この場合には、上述した分割流路115での連通の影響はない。   Further, for example, as shown in FIG. 6 (b), the person in charge of inspection uses a manual pipette or the like to supply liquid from a plurality of (for example, two places) inlets (for example, 113a and 113b) to respective liquid storage portions (for example, 111a and A method of injecting into 111b) is also conceivable. In this case, there is no influence of communication in the divided flow path 115 described above.

しかし、特に多項目診断への対応の場合、注入数が多くなって非常に手間がかかり、また作業が煩雑になるために作業ミス(気泡の混入、注入量過多)の発生する確率が高く、診断精度を低下させてしまうなど、ユーザビリティ低下が大きな問題となる。さらに、一般に注入口は通常の流路よりも大きなスペースを必要とするため、多数の注入口を設けると、マイクロ検査チップが大きくなってしまい、本来の小型、迅速で高精度であるμ−TASのメリットが活かせなくなってしまう。   However, especially when dealing with multi-item diagnosis, the number of injections increases, which is very time-consuming, and the work becomes complicated, so there is a high probability that an operation error (mixing of bubbles, excessive injection amount) will occur. Decreasing usability, such as reducing diagnostic accuracy, is a major problem. Furthermore, since the injection port generally requires a larger space than a normal flow path, if a large number of injection ports are provided, the micro inspection chip becomes large, and the original small, quick and high-precision μ-TAS. The benefits of will be lost.

本発明は、上記課題に鑑みてなされたものであって、微量の液体を簡単な操作で精度よく複数の送液流路に分割して注入することができ、分割して注入した後に安定して送液することのできるマイクロ検査チップおよびマイクロチップの液体分割方法を提供することを目的とする。   The present invention has been made in view of the above problems, and a minute amount of liquid can be divided and injected into a plurality of liquid feeding channels with a simple operation with high accuracy, and is stable after divided injection. It is an object of the present invention to provide a micro inspection chip and a liquid separation method of a micro chip that can be fed in a liquid state.

本発明の目的は、下記構成により達成することができる。   The object of the present invention can be achieved by the following constitution.

1.液体を注入するための液体注入口と、注入された液体を送液する複数の送液流路とを備えたマイクロ検査チップにおいて、
前記液体注入口は、前記液体注入口を封止する蓋と、前記蓋を保持する保持部と、液体を一時的に貯留する液溜り部とを有し、
前記液溜り部は、複数の前記送液流路のそれぞれと連通された複数の連結口を有し、
前記蓋は、前記蓋が前記保持部に挿入された時に、複数の前記連結口を封止して、複数の前記送液流路間の連通を阻止する突起部を有することを特徴とするマイクロ検査チップ。
1. In a micro test chip comprising a liquid inlet for injecting a liquid and a plurality of liquid supply channels for supplying the injected liquid,
The liquid inlet has a lid that seals the liquid inlet, a holding portion that holds the lid, and a liquid reservoir that temporarily stores liquid,
The liquid reservoir has a plurality of connection ports communicated with each of the plurality of liquid supply passages,
The lid has a protrusion that seals the plurality of connection ports and prevents communication between the plurality of liquid supply channels when the lid is inserted into the holding portion. Inspection chip.

2.前記突起部は、前記蓋が前記保持部に挿入された時に前記液溜り部の全部または一部に密着する形状を有し、
前記蓋を前記保持部に挿入することで、
前記突起部によって、前記液溜り部に滴下された液体を複数の前記連結口に押し出し、複数に分割して複数の前記送液流路へ流し込むことを特徴とする前記1に記載のマイクロ検査チップ。
2. The protruding portion has a shape that is in close contact with all or a part of the liquid reservoir when the lid is inserted into the holding portion.
By inserting the lid into the holding part,
2. The micro test chip according to 1 above, wherein the protrusion drops the liquid dropped on the liquid reservoir into a plurality of the connection ports, and divides the liquid into a plurality of flow paths. .

3.液体を注入するための液体注入口と、注入された液体を送液する複数の送液流路とを備えたマイクロ検査チップにおいて、
前記液体注入口は、前記液体注入口を封止する蓋と、前記蓋を保持する保持部と、液体を一時的に貯留する液溜り部とを有し、
複数の前記送液流路は、前記液溜り部の下部に配置され、各々の一部または全部が前記液溜り部の底面に開口しており、
前記蓋は、前記蓋が前記保持部に挿入された時に、複数の前記送液流路を封止して、複数の前記送液流路間の連通を阻止する突起部を有することを特徴とするマイクロ検査チップ。
3. In a micro test chip comprising a liquid inlet for injecting a liquid and a plurality of liquid supply channels for supplying the injected liquid,
The liquid inlet has a lid that seals the liquid inlet, a holding portion that holds the lid, and a liquid reservoir that temporarily stores liquid,
The plurality of liquid supply passages are disposed at the lower part of the liquid reservoir, and a part or all of each is open on the bottom surface of the liquid reservoir,
The lid includes a protrusion that seals the plurality of liquid supply channels and prevents communication between the plurality of liquid channels when the lid is inserted into the holding unit. Micro inspection chip.

4.前記突起部は、前記蓋が前記保持部に挿入された時に前記液溜り部の全部または一部に密着する形状を有し、
前記蓋を前記保持部に挿入することで、
前記突起部によって、前記液溜り部に滴下された液体を複数に分割して複数の前記送液流路へ流し込むことを特徴とする前記3に記載のマイクロ検査チップ。
4). The protruding portion has a shape that is in close contact with all or a part of the liquid reservoir when the lid is inserted into the holding portion.
By inserting the lid into the holding part,
4. The micro test chip according to 3 above, wherein the protrusion drops the liquid dropped into the liquid reservoir part into a plurality of parts and flows into the plurality of liquid supply channels.

5.前記液溜り部および複数の前記送液流路の壁面は、親水性を有することを特徴とする前記3または4に記載のマイクロ検査チップ。   5. 5. The micro test chip according to 3 or 4, wherein the liquid reservoir and the wall surfaces of the plurality of liquid supply channels have hydrophilicity.

6.前記1から5の何れか1項に記載のマイクロ検査チップを用いた液体分割方法において、
前記液溜り部に液体を滴下する滴下工程と、
前記蓋を前記保持部に挿入する挿入工程と、
前記突起部によって、液体を分割して複数の前記送液流路に流し込む分割工程と、
複数の前記送液流路を封止して、複数の前記送液流路間の連通を阻止する分離工程とを備えたことを特徴とするマイクロ検査チップの液体分割方法。
6). In the liquid dividing method using the micro inspection chip according to any one of 1 to 5,
A dropping step of dropping a liquid into the liquid reservoir;
An insertion step of inserting the lid into the holding portion;
A dividing step of dividing the liquid into the plurality of liquid feeding flow paths by the protrusions;
A liquid dividing method for a micro test chip, comprising: a separation step of sealing a plurality of the liquid supply flow paths to prevent communication between the plurality of liquid supply flow paths.

本発明によれば、液体注入口に設けられた液溜り部に貯留された液体を、液溜り部に設けられた複数の連結口を介して、あるいは直接に複数の送液流路に流し込むことで液体を複数に分割することができる。また、液体注入口を封止する蓋に設けられた突起部で複数の連結口あるいは複数の送液流路を封止することで、複数の送液流路間の連通を阻止できる。それによって、微量の液体を簡単な操作で精度よく複数の送液流路に分割して注入することができ、分割して注入した後に安定して送液することのできるマイクロ検査チップおよびマイクロチップの液体分割方法を提供することができる。   According to the present invention, the liquid stored in the liquid reservoir provided in the liquid inlet is poured into the plurality of liquid supply channels through the plurality of connection ports provided in the liquid reservoir or directly. The liquid can be divided into a plurality of pieces. Further, by sealing the plurality of connection ports or the plurality of liquid supply channels with the protrusions provided on the lid that seals the liquid injection port, communication between the plurality of liquid supply channels can be prevented. Thereby, a micro inspection chip and a microchip that can divide and inject a small amount of liquid into a plurality of liquid supply flow paths with a simple operation with high accuracy and can stably supply liquid after divided injection. The liquid dividing method can be provided.

検査装置の一例を示す斜視図である。It is a perspective view which shows an example of an inspection apparatus. 図1に示した検査装置の内部構成の一例を示すブロック図である。It is a block diagram which shows an example of an internal structure of the test | inspection apparatus shown in FIG. マイクロ検査チップの第1の実施の形態を示す模式図である。It is a schematic diagram which shows 1st Embodiment of a micro test | inspection chip. 第1の実施の形態における液体注入口周辺の構成を示す模式図である。It is a schematic diagram which shows the structure of the liquid injection port periphery in 1st Embodiment. 第2の実施の形態における液体注入口周辺の構成を示す模式図である。It is a schematic diagram which shows the structure of the liquid injection port periphery in 2nd Embodiment. 従来の液体の分割方法を示す模式図である。It is a schematic diagram which shows the conventional dividing method of the liquid.

符号の説明Explanation of symbols

1 検査装置
3 トレイ
5 搬送口
7 操作部
9 表示部
100 マイクロ検査チップ
101 流路基板
103 天板
105 流路
107(107a、107b) 送液流路
111 液体貯留部
113 注入口
115 分割流路
117 接続口
151 液体
300 液体注入口
301 蓋
303 保持部
305 ヒンジ
307 液溜り部
309(309a、309b) 連結口
311 突起部
313 漏液受け
315 内壁
DESCRIPTION OF SYMBOLS 1 Inspection apparatus 3 Tray 5 Conveyance port 7 Operation part 9 Display part 100 Micro test | inspection chip 101 Flow path board | substrate 103 Top plate 105 Flow path 107 (107a, 107b) Liquid supply flow path 111 Liquid storage part 113 Inlet 115 Divided flow path 117 Connection port 151 Liquid 300 Liquid injection port 301 Lid 303 Holding part 305 Hinge 307 Liquid reservoir part 309 (309a, 309b) Connection port 311 Protrusion part 313 Leakage receiver 315 Inner wall

以下、本発明を図示の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。なお、図中、同一あるいは同等の部分には同一の番号を付与し、重複する説明は省略する。   Hereinafter, the present invention will be described based on the illustrated embodiment, but the present invention is not limited to the embodiment. In the drawings, the same or equivalent parts are denoted by the same reference numerals, and redundant description is omitted.

まず、本発明のマイクロ検査チップを用いて検査を行うための検査装置について、図1および図2を用いて説明する。図1は、検査装置1の一例を示す斜視図である。   First, an inspection apparatus for performing an inspection using the micro inspection chip of the present invention will be described with reference to FIGS. FIG. 1 is a perspective view showing an example of an inspection apparatus 1.

図1において、検査装置1は、トレイ3、搬送口5、操作部7、表示部9等を備えている。後述する液体注入口から検体や試薬等が注入され、後述する蓋によって液体注入口が封止されたマイクロ検査チップ100は、トレイ3上にセットされ、図示しないローディング機構により、搬送口5から検査装置1内に搬送され、検査が行われる。検査内容や検査対象のデータ等は、操作部7を用いて検査装置1に入力され、検査結果は表示部9に表示される。   In FIG. 1, the inspection apparatus 1 includes a tray 3, a transport port 5, an operation unit 7, a display unit 9, and the like. A micro inspection chip 100 in which a specimen, a reagent, or the like is injected from a liquid injection port described later and the liquid injection port is sealed by a lid described later is set on the tray 3, and is inspected from the transport port 5 by a loading mechanism (not shown). It is conveyed into the apparatus 1 and inspected. Inspection contents, inspection target data, and the like are input to the inspection apparatus 1 using the operation unit 7, and inspection results are displayed on the display unit 9.

図2は、図1に示した検査装置1の内部構成の一例を示すブロック図である。   FIG. 2 is a block diagram showing an example of the internal configuration of the inspection apparatus 1 shown in FIG.

図2において、検査装置1は、マイクロポンプユニット210、加熱冷却ユニット230、検出部250および駆動制御部270等で構成される。マイクロ検査チップ100は、図示しないローディング機構により搬送口5から検査装置1内に搬送され、マイクロポンプユニット210と接続される。マイクロポンプによる送液により、マイクロ検査チップ100内の検体と試薬とが混合されて反応することで、目的物質の検出や病気の判定等の検査が行われる。   In FIG. 2, the inspection apparatus 1 includes a micro pump unit 210, a heating / cooling unit 230, a detection unit 250, a drive control unit 270, and the like. The micro inspection chip 100 is transported from the transport port 5 into the inspection apparatus 1 by a loading mechanism (not shown) and connected to the micro pump unit 210. Tests such as detection of a target substance and determination of disease are performed by mixing and reacting the specimen and reagent in the micro test chip 100 by liquid feeding by a micropump.

マイクロ検査チップ100は、一般に分析チップ、マイクロリアクタチップなどとも称されるものと同等であり、例えば、樹脂、ガラス、シリコン、セラミックスなどを材料とし、その上に、微細加工技術により、幅および高さが数μm〜数百μmのレベルの微細な流路を形成したものである。マイクロ検査チップ100のサイズおよび形状は、通常、縦横が数十mm、厚さが数mm程度の板状である。   The micro inspection chip 100 is equivalent to what is generally called an analysis chip, a microreactor chip, and the like. For example, the micro inspection chip 100 is made of resin, glass, silicon, ceramics, and the like. Is formed with a fine flow path having a level of several μm to several hundred μm. The size and shape of the micro inspection chip 100 is usually a plate shape having a length and width of several tens of mm and a thickness of several mm.

ここでは、マイクロ検査チップ100は、例えばポリプロピレン等の撥水性の樹脂材料で形成されており、試薬や検体等の液体を流すための溝状の流路が表面に形成された流路基板101と、流路基板101の流路が形成された面に接着され、流路基板101の溝状の流路の蓋として機能する天板103とで構成されているとする。流路基板101および天板103には、マイクロポンプユニット210とマイクロ検査チップ100との接続口や、検体や試薬等を注入するための後述する液体注入口が設けられる。   Here, the micro test chip 100 is formed of a water-repellent resin material such as polypropylene, for example, and has a channel substrate 101 on the surface of which a groove-shaped channel for flowing a liquid such as a reagent or a specimen is formed. Suppose that it is composed of a top plate 103 that is bonded to the surface of the flow path substrate 101 on which the flow path is formed and functions as a groove-shaped flow path cover of the flow path substrate 101. The flow path substrate 101 and the top plate 103 are provided with a connection port between the micro pump unit 210 and the micro test chip 100 and a liquid injection port described later for injecting a specimen, a reagent, and the like.

マイクロポンプユニット210は、マイクロ検査チップ100内の送液を行うためのポンプユニットで、マイクロポンプ211、チップ接続部213、駆動液タンク215および駆動液供給部217等で構成される。マイクロポンプユニット210は、1つあるいは複数のマイクロポンプ211を備えている。マイクロポンプ211は、マイクロ検査チップ100内に駆動液216を注入あるいは吸引することで、マイクロ検査チップ100内の送液を行う。チップ接続部213は、マイクロポンプ211とマイクロ検査チップ100とを接続する。   The micro pump unit 210 is a pump unit for performing liquid feeding in the micro test chip 100, and includes a micro pump 211, a chip connection unit 213, a driving liquid tank 215, a driving liquid supply unit 217, and the like. The micropump unit 210 includes one or a plurality of micropumps 211. The micropump 211 feeds the liquid in the micro test chip 100 by injecting or sucking the driving liquid 216 into the micro test chip 100. The chip connection unit 213 connects the micropump 211 and the micro inspection chip 100.

駆動液供給部217は、駆動液タンク215からマイクロポンプ211に駆動液216を供給する。駆動液タンク215は、駆動液216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上には1個または複数個のポンプが形成されており、複数個の場合は、各々独立にあるいは連動して駆動可能である。   The driving liquid supply unit 217 supplies the driving liquid 216 from the driving liquid tank 215 to the micropump 211. The driving liquid tank 215 can be removed and replaced from the driving liquid supply unit 217 to replenish the driving liquid 216. One or a plurality of pumps are formed on the micropump 211, and the plurality of pumps can be driven independently or in conjunction with each other.

マイクロ検査チップ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ている。マイクロポンプ211が駆動されると、マイクロポンプ211から、チップ接続部213を介して、駆動液216がマイクロ検査チップ100に注入あるいは吸引される。マイクロ検査チップ100内の複数の収容部に収容されている検体や試薬等は、駆動液216によってマイクロ検査チップ100内で送液される。   The micro inspection chip 100 and the micropump 211 are connected by a chip connection part 213 and communicated with each other. When the micro pump 211 is driven, the driving liquid 216 is injected or sucked into the micro test chip 100 from the micro pump 211 via the chip connection portion 213. Samples, reagents, and the like housed in a plurality of housing parts in the micro test chip 100 are sent in the micro test chip 100 by the driving liquid 216.

加熱冷却ユニット230は、冷却部231および加熱部233等で構成され、マイクロ検査チップ100内の反応の促進および抑制のために、検体、試薬およびその混合液等の加熱および冷却を行う。冷却部231はペルチエ素子等で構成される。加熱部233は、ヒータ等で構成される。もちろん、加熱部233もペルチエ素子で構成してもよい。   The heating / cooling unit 230 includes a cooling unit 231, a heating unit 233, and the like, and heats and cools a specimen, a reagent, a mixed solution thereof, and the like in order to promote and suppress a reaction in the micro test chip 100. The cooling unit 231 includes a Peltier element or the like. The heating unit 233 includes a heater or the like. Of course, the heating unit 233 may also be formed of a Peltier element.

検出部250は、発光ダイオード(LED)やレーザ等の光源251と、フォトダイオード(PD)等の受光素子253等で構成され、マイクロ検査チップ100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、マイクロ検査チップ100上の検出領域255の位置で光学的に検出する。   The detection unit 250 includes a light source 251 such as a light emitting diode (LED) or a laser, a light receiving element 253 such as a photodiode (PD), and the like, and a target substance contained in a generated liquid obtained by a reaction in the micro inspection chip 100. Is detected optically at the position of the detection region 255 on the micro inspection chip 100.

駆動制御部270は、図示しないマイクロコンピュータやメモリ等で構成され、検査装置1内の各部の駆動、制御、検出等を行う。   The drive control unit 270 includes a microcomputer, a memory, and the like (not shown), and drives, controls, and detects each unit in the inspection apparatus 1.

次に、本発明におけるマイクロ検査チップの第1の実施の形態について、図3および図4を用いて説明する。図3は、本発明におけるマイクロ検査チップ100の第1の実施の形態を示す模式図で、図3(a)は流路基板101側から見た平面図、図3(b)は図3(a)の矢印A側から見た側面図、図3(c)は天板103側から見た平面図である。ここでは、液体注入口300が流路基板101側に設けられた例を示す。   Next, a first embodiment of the micro test chip according to the present invention will be described with reference to FIGS. 3A and 3B are schematic views showing the first embodiment of the micro inspection chip 100 according to the present invention. FIG. 3A is a plan view seen from the flow path substrate 101 side, and FIG. The side view seen from the arrow A side of a), FIG.3 (c) is the top view seen from the top-plate 103 side. Here, an example in which the liquid inlet 300 is provided on the flow path substrate 101 side is shown.

図3(a)において、流路基板101の上には、液体注入口300を構成する保持部303が設けられている。また、流路基板101の天板103側には、破線で図示した流路105が設けられている。保持部303の内部には、液体注入口300に注入された液体を分割するための連結口309が設けられ、液体注入口300の直下には、分割された液体を送液する送液流路107が設けられている。   In FIG. 3A, a holding part 303 constituting the liquid inlet 300 is provided on the flow path substrate 101. Further, a flow path 105 shown by a broken line is provided on the top plate 103 side of the flow path substrate 101. A connection port 309 for dividing the liquid injected into the liquid injection port 300 is provided inside the holding unit 303, and a liquid supply flow path for supplying the divided liquid immediately below the liquid injection port 300. 107 is provided.

図3(b)および(c)において、流路基板101上には、保持部303と、保持部303に挿入されることで液体注入口300を封止する蓋301とが設けられている。保持部303と蓋301とが、例えば柔軟なヒンジ305等で接続されていると、蓋301の落下や紛失の危険がなく、便利である。このような構成としては、例えば特表平9−504608号公報の図5および図6に、スナップ留めの要領で、柔軟なヒンジに取り付けた密封できる蓋を用いて、血液試料を開口部から導入した後にそれを密封する方法が示されている。   3B and 3C, a holding unit 303 and a lid 301 that seals the liquid inlet 300 by being inserted into the holding unit 303 are provided on the flow path substrate 101. If the holding unit 303 and the lid 301 are connected by, for example, a flexible hinge 305 or the like, there is no risk of the lid 301 being dropped or lost, which is convenient. As such a configuration, for example, in FIG. 5 and FIG. 6 of Japanese Patent Publication No. 9-504608, a blood sample is introduced from an opening using a sealable lid attached to a flexible hinge in the manner of snap fastening. After that, how to seal it is shown.

流路基板101の天板103側には、破線で図示した流路105が設けられている。保持部303の内部には、液体注入口300に注入された液体を分割するための連結口309が設けられ、液体注入口300の直下には、分割された液体を送液する送液流路107が設けられている。保持部303と送液流路107とは、連結口309で連通されている。天板103には、流路105とマイクロポンプとを接続する接続口117が設けられている。   On the top plate 103 side of the flow path substrate 101, a flow path 105 illustrated by a broken line is provided. A connection port 309 for dividing the liquid injected into the liquid injection port 300 is provided inside the holding unit 303, and a liquid supply flow path for supplying the divided liquid immediately below the liquid injection port 300. 107 is provided. The holding unit 303 and the liquid supply channel 107 are communicated with each other through a connection port 309. The top plate 103 is provided with a connection port 117 that connects the flow path 105 and the micropump.

図4は、マイクロ検査チップ100の第1の実施の形態における液体注入口300周辺の構成を示す模式図で、図4(a)は図3(b)のB−B’断面図、図4(b)は流路基板101側から見た液体注入口300周辺の平面図である。ここでは液体を2分割する例を示すが、分割数は任意であり、必要に応じて決めればよい。   FIG. 4 is a schematic diagram showing a configuration around the liquid injection port 300 in the first embodiment of the micro test chip 100. FIG. 4A is a cross-sectional view taken along the line BB ′ of FIG. FIG. 5B is a plan view of the periphery of the liquid inlet 300 viewed from the flow path substrate 101 side. Here, an example in which the liquid is divided into two parts is shown, but the number of divisions is arbitrary and may be determined as necessary.

図4(a)および(b)において、液体注入口300は、液体注入口300を封止する蓋301、蓋301を封止状態に保持する保持部303、および液体151を一時的に貯留する液溜り部307等で構成される。   4A and 4B, the liquid inlet 300 temporarily stores a lid 301 that seals the liquid inlet 300, a holding portion 303 that holds the lid 301 in a sealed state, and a liquid 151. It is comprised by the liquid reservoir part 307 grade | etc.,.

蓋301と保持部303とは、蓋301を保持部303に挿入して、保持部303の溝部303aに蓋301の爪部301aを引っ掛けて係止する所謂スナップ留めの形状となっている。もちろん、それ以外の係止方法であってもよい。   The lid 301 and the holding portion 303 have a so-called snap fastening shape in which the lid 301 is inserted into the holding portion 303 and the claw portion 301a of the lid 301 is hooked on the groove portion 303a of the holding portion 303 and locked. Of course, other locking methods may be used.

保持部303は、その内側に、すり鉢状の凹部である液溜り部307を有している。液溜り部307のすり鉢状の斜面の途中には、液溜り部307に注入された液体を複数に分割するための複数の連結口309(ここでは2個の連結口309aと309b)が設けられている。複数の連結口309は、液体151を送液するための複数の送液流路107(ここでは2個の送液流路107aと107b)にそれぞれ連通されている。連結口309および送液流路107の数は、液溜り部307に注入された液体151をいくつに分割する必要があるかの必要な分割数にあわせて決めればよい。   The holding part 303 has a liquid reservoir part 307 which is a mortar-like concave part inside. A plurality of connection ports 309 (here, two connection ports 309a and 309b) for dividing the liquid injected into the liquid storage portion 307 into a plurality of portions are provided in the middle of the mortar-shaped slope of the liquid storage portion 307. ing. The plurality of connection ports 309 are in communication with a plurality of liquid supply channels 107 (here, two liquid supply channels 107a and 107b) for supplying the liquid 151, respectively. The number of the connection ports 309 and the liquid supply channels 107 may be determined according to the required number of divisions for how many portions of the liquid 151 injected into the liquid reservoir 307 need to be divided.

蓋301には、液溜り部307の少なくとも一部の形状を凹凸反転した形状の突起部311が設けられており、蓋301が保持部303に挿入されると、突起部311の面が液溜り部307の面の全部または一部と密着するようになされている。突起部311と液溜り部307とは全く同一の形状でもよいが、本例では、突起部311の先端311aの液溜り部307の底部に当接する部分を除去してある。すなわち、突起部311の先端311aは、液溜り部307の底部に当接しない形状になっている。   The lid 301 is provided with a protrusion 311 having a shape in which at least a part of the liquid reservoir 307 is inverted in shape, and when the lid 301 is inserted into the holding portion 303, the surface of the protrusion 311 collects the liquid. The part 307 is in close contact with all or part of the surface. The protrusion 311 and the liquid reservoir 307 may have exactly the same shape, but in this example, the portion of the tip 311a of the protrusion 311 that contacts the bottom of the liquid reservoir 307 is removed. That is, the tip 311 a of the protrusion 311 has a shape that does not contact the bottom of the liquid reservoir 307.

次に、液体151の分割方法について説明する。まず、作業者によって、ピペット等を用いて、液溜り部307に液体151が滴下される(滴下工程)。続いて、蓋301が図の矢印Z方向に押し下げられて保持部303に挿入される(挿入工程)と、液体151は、液溜り部307と突起部311とに挟まれて連結口309aと309bとの位置まで押し出され、連結口309aと309bとを通って送液流路107aと107bとに流れ出す(分割工程)。従って、蓋301を保持部303に挿入するだけで、液体151を必要な分割数(ここでは2分割)に簡単に精度よく分割することができる。但し、液体151を突起部311によって押し出すことは必須ではない。   Next, a method for dividing the liquid 151 will be described. First, the liquid 151 is dropped into the liquid reservoir 307 by a worker using a pipette or the like (dropping step). Subsequently, when the lid 301 is pushed down in the direction of arrow Z in the drawing and inserted into the holding portion 303 (insertion step), the liquid 151 is sandwiched between the liquid reservoir portion 307 and the projection portion 311 and the connection ports 309a and 309b. Are pushed out to the position of, and flow out to the liquid feeding passages 107a and 107b through the connection ports 309a and 309b (dividing step). Therefore, the liquid 151 can be easily and accurately divided into the required number of divisions (here, two divisions) simply by inserting the lid 301 into the holding portion 303. However, it is not essential to push out the liquid 151 by the protrusion 311.

さらに、蓋301が保持部303に挿入されて、蓋301の爪部301aが保持部303の溝部303aに引っ掛けられて係止されると、液溜り部307の面と突起部311の面とが密着するために、連結口309aと309bとが完全に分離され、送液流路107aと107bとの連通が完全に分離される(分離工程)。これによって、液体151の送液の際のマイクロポンプの力が相互に影響し合って不安定な送液となることがなく、安定した送液が行える。   Further, when the lid 301 is inserted into the holding portion 303 and the claw portion 301a of the lid 301 is hooked and locked in the groove portion 303a of the holding portion 303, the surface of the liquid reservoir portion 307 and the surface of the protruding portion 311 are brought together. In order to be in close contact with each other, the connection ports 309a and 309b are completely separated, and the communication between the liquid supply channels 107a and 107b is completely separated (separation step). Thereby, the force of the micropump at the time of liquid 151 feeding does not affect each other and the liquid feeding becomes unstable, and stable liquid feeding can be performed.

上述したように、マイクロ検査チップ100の第1の実施の形態によれば、液体注入口300の保持部303の内部に設けられた液溜り部307に、液体151の必要な分割数にあわせて、複数の連結口309と複数の送液流路107とを設け、蓋301に液溜り部307の少なくとも一部の形状を凹凸反転した形状の突起部311を設ける。これによって、蓋301を保持部303に挿入するだけで、突起部311の面が液溜り部307の面の全部または一部と密着し、液体151を必要な分割数に簡単に精度よく分割することができる。さらに、複数の送液流路107相互の連通を完全に分離できるので、安定した送液を提供することができる。   As described above, according to the first embodiment of the micro test chip 100, the liquid reservoir 307 provided inside the holding unit 303 of the liquid injection port 300 is matched with the required number of divisions of the liquid 151. A plurality of connection ports 309 and a plurality of liquid supply passages 107 are provided, and a protrusion 311 having a shape obtained by reversing the shape of at least a part of the liquid reservoir 307 on the lid 301 is provided. Thus, just by inserting the lid 301 into the holding portion 303, the surface of the projection 311 is in close contact with all or part of the surface of the liquid reservoir 307, and the liquid 151 is easily and accurately divided into the required number of divisions. be able to. Furthermore, since the communication between the plurality of liquid supply channels 107 can be completely separated, stable liquid supply can be provided.

次に、本発明におけるマイクロ検査チップの第2の実施の形態について、図5を用いて説明する。図5は、マイクロ検査チップ100の第2の実施の形態における液体注入口300周辺の構成を示す模式図で、図5(a)は図5(b)のC−C’断面図、図5(b)は天板103側から見た液体注入口300周辺の平面図である。ここでも液体を2分割する例を示すが、分割数は任意であり、必要に応じて決めればよい。また、ここでは液体注入口300が天板103側に設けられた例を示す。   Next, a second embodiment of the micro test chip according to the present invention will be described with reference to FIG. FIG. 5 is a schematic diagram showing a configuration around the liquid injection port 300 in the second embodiment of the micro test chip 100, and FIG. 5A is a cross-sectional view taken along the line CC ′ of FIG. FIG. 5B is a plan view of the periphery of the liquid inlet 300 viewed from the top plate 103 side. Here, an example in which the liquid is divided into two parts is shown, but the number of divisions is arbitrary and may be determined as necessary. Here, an example in which the liquid inlet 300 is provided on the top plate 103 side is shown.

図5(a)および(b)において、液体注入口300は、液体注入口300を封止する蓋301、蓋301を封止状態に保持する保持部303、液体151を一時的に貯留する液溜り部307、液溜り部307から溢れた液体151を受ける漏液受け313、漏液受け313と液溜り部307とを隔てる内壁315等で構成される。液体注入口300は、流路基板101の天板103側に設けられ、天板103の開口部103aから突出している。   5A and 5B, the liquid inlet 300 includes a lid 301 that seals the liquid inlet 300, a holding portion 303 that holds the lid 301 in a sealed state, and a liquid that temporarily stores the liquid 151. The reservoir 307, the leak receiver 313 that receives the liquid 151 overflowing from the reservoir 307, the inner wall 315 that separates the leak receiver 313 and the reservoir 307, and the like. The liquid inlet 300 is provided on the top plate 103 side of the flow path substrate 101 and protrudes from the opening 103 a of the top plate 103.

蓋301と保持部303とは、蓋301の内壁に設けられた雄ネジと保持部303の外周に設けられた雌ネジとをかみ合わせて係止する所謂ねじ込み式の形状となっている。もちろん、それ以外の係止方法であってもよい。   The lid 301 and the holding portion 303 have a so-called screw-in shape in which a male screw provided on the inner wall of the lid 301 and a female screw provided on the outer periphery of the holding portion 303 are engaged and locked. Of course, other locking methods may be used.

保持部303は、その内側に、液溜り部307から溢れた液体151を受ける漏液受け313を有し、さらにその内側に内壁315を隔てて、円筒状の凹部である液溜り部307を有している。液溜り部307の底面には、液溜り部307に注入された液体を複数に分割して送液するための複数の送液流路107(ここでは2個の送液流路107aと107b)が設けられ、送液流路107aと107bとは、それぞれの一部(図5(b)の斜線部)が液溜り部307の底面に開口して設けられている。送液流路107の数は、液溜り部307に注入された液体151をいくつに分割する必要があるかの必要な分割数にあわせて決めればよい。   The holding part 303 has a liquid leakage receiver 313 that receives the liquid 151 overflowing from the liquid reservoir 307 inside, and further has a liquid reservoir part 307 that is a cylindrical recess with an inner wall 315 interposed therebetween. is doing. On the bottom surface of the liquid reservoir 307, a plurality of liquid supply channels 107 (here, two liquid supply channels 107a and 107b) for dividing and supplying the liquid injected into the liquid reservoir 307 into a plurality of parts. A part of each of the liquid supply channels 107a and 107b (the hatched portion in FIG. 5B) is opened at the bottom surface of the liquid reservoir 307. The number of the liquid supply channels 107 may be determined according to the required number of divisions for how many portions of the liquid 151 injected into the liquid reservoir 307 need to be divided.

蓋301には、液溜り部307の少なくとも一部の形状を凹凸反転した形状の突起部311が設けられており、蓋301が保持部303にねじ込まれると、突起部311の面が液溜り部307の面の全部または一部と密着するようになされている。突起部311と液溜り部307とは、本例のように全く同一の形状でもよいし、一部が異なってもよい。但し、突起部311の先端311aの液溜り部307の底面の送液流路107に当接する部分の形状は、液溜り部307の底面と同じであることが望ましい。   The lid 301 is provided with a protrusion 311 having a shape in which at least a part of the liquid reservoir 307 is inverted in shape. When the lid 301 is screwed into the holding portion 303, the surface of the protrusion 311 becomes the liquid reservoir. 307 is in close contact with all or part of the surface. The protrusion 311 and the liquid reservoir 307 may have the same shape as in this example, or may be partially different. However, it is desirable that the shape of the part of the bottom surface of the liquid reservoir 307 at the tip 311 a of the protrusion 311 that is in contact with the liquid feeding flow path 107 is the same as the bottom surface of the liquid reservoir 307.

次に、液体151の分割方法について説明する。まず、作業者によって、ピペット等を用いて、液溜り部307に液体151が滴下される(滴下工程)。続いて、蓋301が図の矢印Z方向に押し下げられて保持部303にねじ込まれる(挿入工程)と、液体151は、液溜り部307と突起部311とに挟まれて押し出され、液溜り部307の底面に設けられた送液流路107aおよび107bの開口部を通って、送液流路107aと107bとに流れ出す(分割工程)。従って、蓋301を保持部303にねじ込むだけで、液体151を必要な分割数(ここでは2分割)に簡単に精度よく分割することができる。但し、液体151を突起部311によって押し出すことは必須ではない。   Next, a method for dividing the liquid 151 will be described. First, the liquid 151 is dropped into the liquid reservoir 307 by a worker using a pipette or the like (dropping step). Subsequently, when the lid 301 is pushed down in the direction of arrow Z in the figure and screwed into the holding portion 303 (insertion process), the liquid 151 is pushed out by being sandwiched between the liquid reservoir portion 307 and the projection portion 311. The liquid flows through the openings of the liquid supply channels 107a and 107b provided on the bottom surface of 307 and flows out into the liquid supply channels 107a and 107b (division step). Therefore, the liquid 151 can be easily and accurately divided into the required number of divisions (here, two divisions) simply by screwing the lid 301 into the holding portion 303. However, it is not essential to push out the liquid 151 by the protrusion 311.

さらに、蓋301が保持部303にねじ込まれると、液溜り部307の面と突起部311の面とが密着するために、送液流路107aと107bとの連通が完全に分離される(分離工程)。これによって、液体151の送液の際のマイクロポンプの力が相互に影響し合って不安定な送液となることがなく、安定した送液が行える。   Further, when the lid 301 is screwed into the holding portion 303, the surface of the liquid reservoir 307 and the surface of the protrusion 311 are in close contact with each other, so that the communication between the liquid supply channels 107a and 107b is completely separated (separation). Process). Thereby, the force of the micropump at the time of liquid 151 feeding does not affect each other and the liquid feeding becomes unstable, and stable liquid feeding can be performed.

なお、液溜り部307および送液流路107aと107bの壁面は、蓋301を保持部303にねじ込んだ際に、液体151を液溜り部307から送液流路107aおよび107bにスムーズに流し込むために、親水性であることが望ましい。親水性のレベルは流路の寸法や形状等により異なるが、目安として壁面と純水との接触角が50°以下が好ましく、30°以下がより好ましい。   The liquid reservoir 307 and the wall surfaces of the liquid supply channels 107a and 107b are used to smoothly flow the liquid 151 from the liquid reservoir 307 into the liquid supply channels 107a and 107b when the lid 301 is screwed into the holding unit 303. In addition, it is desirable to be hydrophilic. The hydrophilic level varies depending on the dimensions and shape of the flow path, but as a guide, the contact angle between the wall surface and pure water is preferably 50 ° or less, more preferably 30 ° or less.

液溜まり部307および送液流路107aと107bの壁面が親水性の場合、滴下された検体151は、自発的に送液流路107aおよび107bに流れ込む。この場合、蓋301の突起部311で液体151を押し出す必要がなく、突起部311は、送液流路107aと107bを分離する役割を果たす。   When the liquid reservoir 307 and the wall surfaces of the liquid supply channels 107a and 107b are hydrophilic, the dropped sample 151 spontaneously flows into the liquid supply channels 107a and 107b. In this case, the liquid 151 does not need to be pushed out by the protrusion 311 of the lid 301, and the protrusion 311 plays a role of separating the liquid supply channels 107a and 107b.

蓋301を保持部303にねじ込んだ時に液溜り部307から溢れた液体151は、漏液受け313に流れ込むため、液体151が例えば危険なウイルス等を含む検体であっても、マイクロ検査チップ100の外部に漏れ出すことはなく、安全が保たれる。   Since the liquid 151 overflowing from the liquid reservoir 307 when the lid 301 is screwed into the holding part 303 flows into the leak receiver 313, even if the liquid 151 is a specimen containing, for example, a dangerous virus or the like, There is no leakage to the outside, and safety is maintained.

上述したように、マイクロ検査チップ100の第2の実施の形態によれば、液体注入口300の保持部303の内部に設けられた液溜り部307の下部に、液体151の必要な分割数にあわせて、複数の送液流路107を設けて液溜り部307の底部に開口させ、蓋301に液溜り部307の少なくとも一部の形状を凹凸反転した形状の突起部311を設ける。これによって、蓋301を保持部303にねじ込むだけで、突起部311の面が液溜り部307の面の全部または一部と密着し、液体151を必要な分割数に簡単に精度よく分割することができる。さらに、複数の送液流路107相互の連通を完全に分離できるので、安定した送液を提供することができる。   As described above, according to the second embodiment of the micro inspection chip 100, the required number of divisions of the liquid 151 is provided below the liquid reservoir 307 provided inside the holding unit 303 of the liquid inlet 300. In addition, a plurality of liquid supply passages 107 are provided and opened at the bottom of the liquid reservoir 307, and a protrusion 311 having a shape obtained by reversing the shape of at least a part of the liquid reservoir 307 on the lid 301 is provided. Thus, the surface of the protrusion 311 is in close contact with all or part of the surface of the liquid reservoir 307 simply by screwing the lid 301 into the holding portion 303, and the liquid 151 is easily and accurately divided into the necessary number of divisions. Can do. Furthermore, since the communication between the plurality of liquid supply channels 107 can be completely separated, stable liquid supply can be provided.

以上に述べたように、本発明によれば、液体注入口に設けられた液溜り部に貯留された液体を、液溜り部に設けられた複数の連結口を介して、あるいは直接に複数の送液流路に流し込むことで液体を複数に分割することができる。また、液体注入口を封止する蓋に設けられた突起部で複数の連結口を封止することで、複数の送液流路間の連通を阻止できる。それによって、微量の液体を簡単な操作で精度よく複数の送液流路に分割して注入することができ、分割して注入した後に安定して送液することのできるマイクロ検査チップおよびマイクロチップの液体分割方法を提供することができる。   As described above, according to the present invention, the liquid stored in the liquid reservoir provided in the liquid inlet is supplied to the plurality of connection ports provided in the liquid reservoir or directly. The liquid can be divided into a plurality of parts by pouring into the liquid feed flow path. Further, by sealing the plurality of connection ports with the protrusions provided on the lid that seals the liquid injection port, communication between the plurality of liquid supply channels can be prevented. Thereby, a micro inspection chip and a microchip that can divide and inject a small amount of liquid into a plurality of liquid supply flow paths with a simple operation with high accuracy and can stably supply liquid after divided injection. The liquid dividing method can be provided.

尚、本発明に係るマイクロ検査チップおよびマイクロチップの液体分割方法を構成する各構成の細部構成および細部動作に関しては、本発明の趣旨を逸脱することのない範囲で適宜変更可能である。   The detailed configuration and detailed operation of each component constituting the micro inspection chip and the microchip liquid dividing method according to the present invention can be changed as appropriate without departing from the spirit of the present invention.

Claims (6)

液体を注入するための液体注入口と、注入された液体を分割して送液する複数の送液流路とを備えたマイクロ検査チップにおいて、
前記液体注入口は、前記液体注入口を封止する蓋と、前記蓋を保持する保持部と、液体を一時的に貯留する液溜り部とを有し、
前記液溜り部は、複数の前記送液流路のそれぞれと連通された複数の連結口を有し、
前記蓋は、前記蓋が前記保持部に挿入された時に、複数の前記送液流路間の連通を阻止する突起部を有することを特徴とするマイクロ検査チップ。
In a micro inspection chip comprising a liquid inlet for injecting liquid and a plurality of liquid supply passages for dividing and supplying the injected liquid,
The liquid inlet has a lid that seals the liquid inlet, a holding portion that holds the lid, and a liquid reservoir that temporarily stores liquid,
The liquid reservoir has a plurality of connection ports communicated with each of the plurality of liquid supply passages,
The micro inspection chip according to claim 1, wherein the lid has a protrusion that prevents communication between the plurality of liquid supply channels when the lid is inserted into the holding portion.
前記突起部は、前記蓋が前記保持部に挿入された時に前記液溜り部の全部または一部に密着する形状を有し、
前記蓋を前記保持部に挿入することで、
前記突起部によって、前記液溜り部に滴下された液体を複数の前記連結口に押し出し、複数に分割して複数の前記送液流路へ流し込むことを特徴とする請求の範囲第1項に記載のマイクロ検査チップ。
The protruding portion has a shape that is in close contact with all or a part of the liquid reservoir when the lid is inserted into the holding portion.
By inserting the lid into the holding part,
2. The liquid according to claim 1, wherein the protrusion drops the liquid dropped into the liquid reservoir into the plurality of connection ports, and divides the liquid into a plurality of flow paths. Micro inspection chip.
液体を注入するための液体注入口と、注入された液体を分割して送液する複数の送液流路とを備えたマイクロ検査チップにおいて、
前記液体注入口は、前記液体注入口を封止する蓋と、前記蓋を保持する保持部と、液体を一時的に貯留する液溜り部とを有し、
複数の前記送液流路は、前記液溜り部の下部に配置され、各々の一部または全部が前記液溜り部の底面に開口しており、
前記蓋は、前記蓋が前記保持部に挿入された時に、複数の前記送液流路間の連通を阻止する突起部を有することを特徴とするマイクロ検査チップ。
In a micro inspection chip comprising a liquid inlet for injecting liquid and a plurality of liquid supply passages for dividing and supplying the injected liquid,
The liquid inlet has a lid that seals the liquid inlet, a holding portion that holds the lid, and a liquid reservoir that temporarily stores liquid,
The plurality of liquid supply passages are disposed at the lower part of the liquid reservoir, and a part or all of each is open on the bottom surface of the liquid reservoir,
The micro inspection chip according to claim 1, wherein the lid has a protrusion that prevents communication between the plurality of liquid supply channels when the lid is inserted into the holding portion.
前記突起部は、前記蓋が前記保持部に挿入された時に前記液溜り部の全部または一部に密着する形状を有し、
前記蓋を前記保持部に挿入することで、
前記突起部によって、前記液溜り部に滴下された液体を複数に分割して複数の前記送液流路へ流し込むことを特徴とする請求の範囲第3項に記載のマイクロ検査チップ。
The protruding portion has a shape that is in close contact with all or a part of the liquid reservoir when the lid is inserted into the holding portion.
By inserting the lid into the holding part,
The micro test chip according to claim 3, wherein the liquid dropped into the liquid reservoir is divided into a plurality of parts and poured into the plurality of liquid supply channels by the protrusions.
前記液溜り部および複数の前記送液流路の壁面は、親水性を有することを特徴とする請求の範囲第3項または第4項に記載のマイクロ検査チップ。   The micro test chip according to claim 3 or 4, wherein the liquid reservoir and the wall surfaces of the plurality of liquid supply channels have hydrophilicity. 請求の範囲第1項から第5項の何れか1項に記載のマイクロ検査チップを用いた液体分割方法において、
前記液溜り部に液体を滴下する滴下工程と、
前記蓋を前記保持部に挿入する挿入工程と、
前記突起部によって、液体を分割して複数の前記送液流路に流し込む分割工程と、
複数の前記送液流路を封止して、複数の前記送液流路間の連通を阻止する分離工程とを備えたことを特徴とするマイクロ検査チップの液体分割方法。
In the liquid dividing method using the micro inspection chip according to any one of claims 1 to 5,
A dropping step of dropping a liquid into the liquid reservoir;
An insertion step of inserting the lid into the holding portion;
A dividing step of dividing the liquid into the plurality of liquid feeding flow paths by the protrusions;
A liquid dividing method for a micro test chip, comprising: a separation step of sealing a plurality of the liquid supply flow paths to prevent communication between the plurality of liquid supply flow paths.
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