JP5268402B2 - Quantitative device - Google Patents

Quantitative device Download PDF

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JP5268402B2
JP5268402B2 JP2008076911A JP2008076911A JP5268402B2 JP 5268402 B2 JP5268402 B2 JP 5268402B2 JP 2008076911 A JP2008076911 A JP 2008076911A JP 2008076911 A JP2008076911 A JP 2008076911A JP 5268402 B2 JP5268402 B2 JP 5268402B2
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branch point
liquid
rotation center
liquid branch
chamber
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JP2009229324A (en
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知裕 来島
博司 佐伯
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Panasonic Corp
Panasonic Holdings Corp
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Panasonic Corp
Matsushita Electric Industrial Co Ltd
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Priority to JP2008076911A priority Critical patent/JP5268402B2/en
Application filed by Panasonic Corp, Matsushita Electric Industrial Co Ltd filed Critical Panasonic Corp
Priority to EP08848318.5A priority patent/EP2219034B1/en
Priority to CN2008801077592A priority patent/CN101802622B/en
Priority to CN201310443484.2A priority patent/CN103487596B/en
Priority to US12/741,929 priority patent/US9182384B2/en
Priority to CN201310443482.3A priority patent/CN103499702B/en
Priority to PCT/JP2008/003222 priority patent/WO2009060617A1/en
Publication of JP2009229324A publication Critical patent/JP2009229324A/en
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Publication of JP5268402B2 publication Critical patent/JP5268402B2/en
Priority to US14/877,663 priority patent/US10101317B2/en
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a quantification device capable of performing quantitative transfer into a chamber, even when a liquid branch point of a capillary channel is not on the same circumference. <P>SOLUTION: A sectional area of a channel of a connection part to a measuring chamber 5 receiving a distribution of sample liquid from a liquid branch point 17 having a shorter distance to a rotation center 13 is formed larger than a sectional area of a connection part E to a liquid branch point 16, in quantification parts 9, 10 having each different distance between the rotation center 13 and each liquid branch point 16, 17. Consequently, introduction of the sample liquid into the measuring chamber is facilitated, and dispersion of a liquid amount with a measuring chamber 6 can be reduced. <P>COPYRIGHT: (C)2010,JPO&amp;INPIT

Description

本発明は、医療分野におけるサンプル液としての血液の成分分析や、その他の各種のサンプル液の成分分析に使用される定量デバイスに関するものである。   The present invention relates to a quantitative device used for component analysis of blood as a sample solution in the medical field and other component analysis of various sample solutions.

従来、マイクロ流路を形成したマイクロチップを用いて生物学的流体を電気化学的にあるいは光学的に分析する方法がある。電気化学的に分析する方法としては、試料液中の特定の成分を分析するバイオセンサーとして、例えば、血液中のグルコースとセンサー中に担持したグルコースオキシダーゼ等の試薬との反応により得られる電流値を測定することにより、血糖値などを求めるものがある。   Conventionally, there is a method of electrochemically or optically analyzing a biological fluid using a microchip in which a microchannel is formed. As a method for electrochemical analysis, as a biosensor for analyzing a specific component in a sample solution, for example, a current value obtained by a reaction between glucose in blood and a reagent such as glucose oxidase supported in the sensor is obtained. Some measure blood glucose levels by measuring them.

また、マイクロチップを用いて分析する方法では、水平軸を有する回転装置を使って流体の制御をすることが可能であり、遠心力を利用して試料液の計量、細胞質材料の分離、分離された流体の移送分配、液体の混合/攪拌等を行うことができるため、種々の生物化学的な分析を行うことが可能である。   In the analysis method using a microchip, the fluid can be controlled using a rotating device having a horizontal axis, and the sample liquid is measured, the cytoplasmic material is separated and separated using a centrifugal force. Therefore, various biochemical analyzes can be performed.

図１０は特許文献１などに見られる遠心移送式バイオセンサ４００を示し、マイクロチップに導入したサンプル液を一度に複数定量して分析することができる。これは、サンプル液を入口ポート４０９から出口ポート４１０まで毛細管力で移送し、各毛細管流路４０４ａ〜４０４ｆをサンプル液で満たした後、バイオセンサ４００の回転によって発生する遠心力によって、それぞれの毛細管流路内の試料液を同一円周上に配置された液分岐点４０６ａ〜４０６ｇで分配し、各連結微小導管４０７ａ〜４０７ｆを通って、次の処理室（図示省略）へ移送される。
特表２００５−５０２０３１号公報 FIG. 10 shows a centrifugal transfer biosensor 400 found in Patent Document 1 and the like, and a plurality of sample liquids introduced into a microchip can be quantified and analyzed at a time. This is because the sample liquid is transferred by capillary force from the inlet port 409 to the outlet port 410, and each capillary channel 404a to 404f is filled with the sample liquid, and then each capillary tube is generated by the centrifugal force generated by the rotation of the biosensor 400. The sample liquid in the flow channel is distributed at the liquid branch points 406a to 406g arranged on the same circumference, and is transferred to the next processing chamber (not shown) through each connected microconduit 407a to 407f.
JP 2005-502031 A

しかしながら、前記従来の構成において、複数ある液分岐点が同一円周上にない場合、遠心力でサンプル液を移送すると、回転中心から毛細管流路の液分岐点までの距離が短い流路から移送が開始され、先のチャンバー内で定量できていないという課題を有している。   However, in the conventional configuration, when a plurality of liquid branch points are not on the same circumference, when the sample liquid is transferred by centrifugal force, the distance from the center of rotation to the liquid branch point of the capillary channel is transferred from a short channel. Has been started and has a problem that it cannot be quantified in the previous chamber.

本発明は、前記従来の課題を解決するもので、毛細管流路の液分岐点が同一円周上になくても測定チャンバーに定量を移送できる定量デバイスを提供することを目的とする。   An object of the present invention is to solve the above-mentioned conventional problems, and to provide a quantitative device capable of transferring a quantitative amount to a measurement chamber even when the liquid branch points of the capillary channel are not on the same circumference.

本発明の請求項１記載の定量デバイスは、充填用チャンバーのサンプル液を複数の測定チャンバーに分配するために回転中心の回りに回転させて使用する定量デバイスであって、前記回転中心に対して前記複数の測定チャンバーを外周側に沿って配置し、基端が前記充填用チャンバーに接続され蛇行しながら前記回転中心と前記複数の測定チャンバーの間を周方向に延長され内周側の変曲点を液分岐点として前記複数の測定チャンバーにサンプル液を分配する接続部を有する定量毛細管流路を設け、前記回転中心と液分岐点との距離が異なる部分では、前記回転中心と液分岐点との距離が短い方の液分岐点からサンプル液の分配を受ける測定チャンバーとの接続部の流路の断面積が、前記回転中心と液分岐点との距離が長い方の液分岐点に接続された流路と前記回転中心と液分岐点との距離が短い方の液分岐点に接続された流路との接続部の断面積よりも大きいことを特徴とする。   The quantitative device according to claim 1 of the present invention is a quantitative device that is used by rotating around a rotation center in order to distribute the sample liquid in the filling chamber to a plurality of measurement chambers. The plurality of measurement chambers are arranged along the outer peripheral side, and a base end is connected to the filling chamber and meanderingly extends between the rotation center and the plurality of measurement chambers in a circumferential direction and is bent on the inner peripheral side. A fixed capillary channel having a connection part for distributing the sample liquid to the plurality of measurement chambers with the point as a liquid branch point is provided, and at a portion where the distance between the rotation center and the liquid branch point is different, the rotation center and the liquid branch point The cross-sectional area of the flow path at the connection with the measurement chamber that receives the distribution of the sample liquid from the liquid branch point with the shorter distance to the liquid branch point is in contact with the liquid branch point with the longer distance between the rotation center and the liquid branch point. Flow paths and being larger than the cross-sectional area of the connecting portion between the rotation center and the liquid branch point and flow path length is connected to the shorter of the liquid branch point.

本発明の請求項２記載の定量デバイスは、請求項１において、前記定量部と前記チャンバーの接続部の面積は、Ｘ＝γ／（ｍ・ｒ・ω２／Ｓ）、Ｘ：拡張に必要な長さ、ｍ：分子の質量、ｒ：回転半径、ω：回転数、Ｓ：断面積、γ：表面張力、で示される長さを、前記定量部と定量部の接続部の流路幅もしくは厚みに足した長さで表されることを特徴とする。 The quantitative device according to claim 2 of the present invention is the quantitative device according to claim 1, wherein the area of the connecting portion between the quantitative portion and the chamber is X = γ / (m · r · ω 2 / S), X: required for expansion Length, m: molecular mass, r: radius of rotation, ω: rotational speed, S: cross-sectional area, γ: surface tension, and the flow path width of the connecting portion between the quantification unit and the quantification unit Or it is represented by the length added to thickness.

本発明の請求項３記載の定量デバイスは、請求項１において、流路および測定チャンバーの壁面には親水処理が施されていることを特徴とする。   The quantitative device according to claim 3 of the present invention is characterized in that, in claim 1, the flow path and the wall surface of the measurement chamber are subjected to hydrophilic treatment.

本発明の定量デバイスによれば、毛細管流路の液分岐点の位置が回転中心から異なる距離にあっても定量毛細管流路内で定量されたサンプル液をチャンバー内に移送することができる。   According to the quantitative device of the present invention, the sample liquid quantified in the quantitative capillary channel can be transferred into the chamber even if the position of the liquid branch point of the capillary channel is at a different distance from the rotation center.

以下に、本発明の実施の形態を図１〜図９に基づいて説明する。
図１〜図７は本発明の実施の形態を示し、図８と図９は比較例を示す。
本発明の実施の形態の定量デバイスは、図１と図２に示すように微細な凹凸形状を表面に有するマイクロチャネル構造が形成されたベース基板３１と、ベース基板３１の上面を覆うカバー基板３２とを貼り合わせて構成されており、説明の都合上、図１ではカバー基板３２を取り除いた状態で図示されている。 Hereinafter, embodiments of the present invention will be described with reference to FIGS.
1 to 7 show an embodiment of the present invention, and FIGS. 8 and 9 show comparative examples.
As shown in FIGS. 1 and 2, the quantitative device according to the embodiment of the present invention includes a base substrate 31 on which a microchannel structure having fine irregularities on the surface is formed, and a cover substrate 32 that covers the upper surface of the base substrate 31. For convenience of explanation, FIG. 1 is shown with the cover substrate 32 removed.

ベース基板３１には、充填用チャンバー１、測定チャンバー３，４，５，６、廃棄用チャンバー７、空気穴チャンバー２４，２５と、定量毛細管流路２が形成されている。図１において各凹部の位置に示された孔３３ａ，３３ｂ，３３ｃ，３３ｄ，３３ｅ，３３ｆ，３３ｇ，３３ｈは、図２に示すようにベース基板３１に形成されており大気に連通している。   The base substrate 31 is formed with a filling chamber 1, measurement chambers 3, 4, 5, 6, a disposal chamber 7, air hole chambers 24, 25, and a quantitative capillary channel 2. 1, holes 33a, 33b, 33c, 33d, 33e, 33f, 33g, and 33h shown in FIG. 1 are formed in the base substrate 31 as shown in FIG. 2, and communicate with the atmosphere.

回転中心１３に対して測定チャンバー３〜６は外周側に沿って配置されている。定量毛細管流路２は、基端が充填用チャンバー１に接続され蛇行しながら回転中心１３と測定チャンバー３〜６の間を周方向に延長され内周側の変曲点を液分岐点１４，１５，１６，１７，１８として、各液分岐点で分岐されたサンプル液を測定チャンバー３〜６に分配する接続部１９，２０，２１，２２を有し、また定量毛細管流路２は、接続部２３から廃棄用チャンバー７へ余ったサンプル液を配る。   The measurement chambers 3 to 6 are arranged along the outer peripheral side with respect to the rotation center 13. The fixed capillary channel 2 has a proximal end connected to the filling chamber 1 while meandering and extending between the rotation center 13 and the measurement chambers 3 to 6 in the circumferential direction, and the inflection point on the inner circumference side is a liquid branch point 14. 15, 16, 17, and 18 have connecting portions 19, 20, 21, and 22 that distribute the sample liquid branched at each liquid branch point to the measurement chambers 3 to 6, and the fixed capillary channel 2 is connected The surplus sample solution is distributed from the section 23 to the disposal chamber 7.

充填用チャンバー１にサンプル液を充填すると、サンプル液は毛細管力により定量毛細管流路２を満たす。このとき空気穴として設けられたのが空気穴用チャンバー２４，２５である。この定量毛細管流路２は同形状の流路が複数連なっており回転中心１３側に液分岐点、外周方向へ測定用チャンバー３，４，５，６へサンプル液を導入するための接続部１９〜２３を繰り返す構成となっている。   When the filling chamber 1 is filled with the sample liquid, the sample liquid fills the fixed capillary channel 2 by capillary force. At this time, the air hole chambers 24 and 25 are provided as air holes. The fixed capillary channel 2 has a plurality of channels having the same shape, and a connection point 19 for introducing the sample solution into the measurement chambers 3, 4, 5, 6 in the outer peripheral direction at the liquid branch point on the rotation center 13 side. It is the structure which repeats ~ 23.

サンプル液が定量毛細管流路２を満たした状態で、この定量デバイスを回転中心１３を中心として回転させることで遠心力をかけると、定量毛細管流路２内のサンプル液は定量毛細管流路２の液分岐点から左右に分断され測定チャンバー３，４，５，６内および充填チャンバー１、廃棄用チャンバー７に移送される。   When a centrifugal force is applied by rotating the quantitative device around the rotation center 13 in a state where the sample liquid fills the quantitative capillary channel 2, the sample liquid in the quantitative capillary channel 2 is in the quantitative capillary channel 2. It is divided from the liquid branch point to the left and right, and transferred to the measurement chambers 3, 4, 5, 6, the filling chamber 1 and the disposal chamber 7.

定量毛細管流路２には、図３に仮想線で示すように定量部８，９，１０，１１が形成されている。各定量部８，９，１０，１１の外周方向には、測定チャンバー３，４，５，６がそれぞれ配置されている。このとき各測定チャンバー３，４，５，６に要するサンプル液の量は、定量毛細管流路２内の各液分岐点１４から液分岐点１８までで区切られた定量部８，９，１０，１１の容量である。定量部８，９は３マイクロリットル、定量部１０，１１は７マイクロリットルが導入されるよう設計されている。   In the fixed capillary channel 2, fixed portions 8, 9, 10, and 11 are formed as shown by phantom lines in FIG. 3. Measurement chambers 3, 4, 5, and 6 are arranged in the outer peripheral direction of each of the quantification units 8, 9, 10, and 11, respectively. At this time, the amount of sample liquid required for each of the measurement chambers 3, 4, 5, and 6 is determined by the quantification units 8, 9, 10, and 6 separated from each liquid branch point 14 to the liquid branch point 18 in the quantitative capillary channel 2. 11 capacity. The quantification units 8 and 9 are designed to introduce 3 microliters, and the quantification units 10 and 11 are designed to introduce 7 microliters.

この実施の形態では、定量部１０と測定チャンバー５との接続部２１に、図４〜図６に示す特徴的な手段３４が設けられている。
この特徴的な手段３４の説明に先立って、比較例を説明する。 In this embodiment, the characteristic means 34 shown in FIGS. 4 to 6 is provided in the connection part 21 between the quantitative unit 10 and the measurement chamber 5.
Prior to the description of the characteristic means 34, a comparative example will be described.

図８に示した比較例では、接続部２１に特徴的な手段３４が設けられていないだけで、その他は図１〜図３と構成が同一である。
図９（ａ）に示すように、充填用チャンバー１に充填したサンプル液が毛細管力により定量毛細管流路２を満たしている状態で、回転中心１３を中心として例えば４０００ｒｐｍで回転させて遠心力をかけると、図９（ｂ）に示すように定量毛細管流路２内に保持しているサンプル液が、図９（ｃ）に示すように液分岐点で分断され各測定チャンバー３，４，５，６に移送される。この定量毛細管流路２に保持する量が多くなると、毛細管流路の幅や長さを変更する必要があるが、毛細管力を均一に保持するため定量毛細管流路２の長さを変更すると、回転中心１３から液分岐点１７，１８までの距離が液分岐点１４，１５，１６に比べ短くなる。遠心力による液の移送は回転中心１３から外周方向に広がるため、サンプル液が移送され始めるのは回転中心１３からの距離が短い液分岐点１７，１８からとなる。よって、回転中心１３から距離の長い液分岐点１４，１５，１６の場合は、回転中心１３からの距離が短い液分岐点１７，１８の流路に比べて遅れて移送されることになる。ここで定量部９と定量部１０が隣接する部分では、先に移送が開始された液分岐点１７のサンプル液が測定チャンバー５に導入されず定量部９へ流れ込んでしまう。 In the comparative example shown in FIG. 8, only the characteristic means 34 is not provided in the connection portion 21, and the other configurations are the same as those in FIGS. 1 to 3.
As shown in FIG. 9A, in a state where the sample liquid filled in the filling chamber 1 fills the fixed capillary flow path 2 by capillary force, the centrifugal force is rotated by rotating at, for example, 4000 rpm around the rotation center 13. As shown in FIG. 9 (b), the sample liquid held in the fixed capillary channel 2 is divided at the liquid branch point as shown in FIG. , 6. When the amount held in the quantitative capillary channel 2 increases, it is necessary to change the width and length of the capillary channel, but in order to keep the capillary force uniform, if the length of the quantitative capillary channel 2 is changed, The distance from the rotation center 13 to the liquid branch points 17 and 18 is shorter than the liquid branch points 14, 15 and 16. Since the transfer of the liquid by centrifugal force spreads from the rotation center 13 in the outer peripheral direction, the sample liquid starts to be transferred from the liquid branch points 17 and 18 having a short distance from the rotation center 13. Therefore, in the case of the liquid branch points 14, 15, 16 having a long distance from the rotation center 13, the liquid branch points 14, 15, 16 are transferred later than the flow paths of the liquid branch points 17, 18 having a short distance from the rotation center 13. Here, in the portion where the quantification unit 9 and the quantification unit 10 are adjacent, the sample liquid at the liquid branch point 17 that has been transferred first flows into the quantification unit 9 without being introduced into the measurement chamber 5.

よって、図９（ｃ）に示すように定量毛細管流路２のサンプル液を移送し終わった状態では、測定チャンバー３，４，５，６のサンプル液の量にばらつきがある。これは回転開始の直後では回転数が低いため遠心力が弱いことと、定量毛細管流路２はサンプル液で満たされているため、各定量部８，９，１０，１１と各測定チャンバー３，４，５，６の接続部で働く表面張力より定量部同士が接続する部分での表面張力のほうが弱いため、低速回転時での遠心力ではサンプル液を測定チャンバー内には導入させることができず、サンプル液で満たされている隣の流路内へ流れ込ませてしまう。その結果、回転中心１３から前記液分岐点までの距離が同じ場所からサンプル液を受け入れている測定チャンバー３，４を見ると、測定チャンバー５へ供給するはずのサンプル液の一部が図９（ｂ）に矢印で示すように測定チャンバー４に流入するため、測定チャンバー４のサンプル液の量が測定チャンバー３のサンプル液の量よりも多くなって、測定チャンバー３と測定チャンバー４とでサンプル液の量がばらつく。また、回転中心１３から前記液分岐点までの距離が同じ場所からサンプル液を受け入れている測定チャンバー５，６を見ると、測定チャンバー５へ供給するはずのサンプル液の一部が図９（ｂ）に矢印で示すように測定チャンバー４に流入して失われているため、測定チャンバー５のサンプル液の量が測定チャンバー６のサンプル液の量よりも少なくなって、測定チャンバー５と測定チャンバー６とでサンプル液の量がばらつく。   Therefore, as shown in FIG. 9C, in the state where the sample liquid in the fixed capillary channel 2 has been transferred, the amount of the sample liquid in the measurement chambers 3, 4, 5, and 6 varies. This is because the centrifugal force is weak because the rotational speed is low immediately after the start of rotation, and because the quantitative capillary channel 2 is filled with the sample liquid, each quantitative unit 8, 9, 10, 11 and each measurement chamber 3, Since the surface tension at the part where the determination parts are connected is weaker than the surface tension acting at the connection part of 4, 5 and 6, the sample solution can be introduced into the measurement chamber by centrifugal force at low speed rotation. Instead, it flows into the adjacent flow path filled with the sample liquid. As a result, when viewing the measurement chambers 3 and 4 receiving the sample liquid from the same location from the rotation center 13 to the liquid branch point, a part of the sample liquid to be supplied to the measurement chamber 5 is shown in FIG. Since the liquid flows into the measurement chamber 4 as indicated by an arrow in b), the amount of the sample liquid in the measurement chamber 4 becomes larger than the amount of the sample liquid in the measurement chamber 3, and the sample liquid in the measurement chamber 3 and the measurement chamber 4. The amount of fluctuates. Further, when viewing the measurement chambers 5 and 6 that receive the sample liquid from the same distance from the rotation center 13 to the liquid branch point, a part of the sample liquid to be supplied to the measurement chamber 5 is shown in FIG. ), The amount of the sample liquid in the measurement chamber 5 is smaller than the amount of the sample liquid in the measurement chamber 6, and the measurement chamber 5 and the measurement chamber 6 are lost. And the amount of sample solution varies.

測定チャンバー３と測定チャンバー４とのサンプル液の液量のばらつきを低減し、測定チャンバー５と測定チャンバー６とのサンプル液の液量のばらつきを低減することを目的として、この実施の形態では図４〜図６に示す特徴的な手段３４が設けられている。この特徴的な手段３４は、回転中心と液分岐点との距離が異なる部分では、前記回転中心と液分岐点との距離が短い方の液分岐点からサンプル液の分配を受ける測定チャンバーとの接続部の流路の断面積が、前記回転中心と液分岐点との距離が長い方の液分岐点に接続された流路と前記回転中心と液分岐点との距離が短い方の液分岐点に接続された流路との接続部の断面積よりも大きくして測定チャンバー５内に流れ易くした。これにより遠心力による液の移送の際にサンプル液が測定チャンバー５内へ流れ易くなり隣の定量部９へ侵入する前に測定チャンバー５に導入させて各測定チャンバーに導入されるサンプル液の量も定量にしようとするものである。   In this embodiment, in order to reduce the variation in the amount of sample liquid between the measurement chamber 3 and the measurement chamber 4 and to reduce the variation in the amount of sample liquid between the measurement chamber 5 and the measurement chamber 6, Characteristic means 34 shown in FIGS. 4 to 6 are provided. This characteristic means 34 is used in a portion where the distance between the rotation center and the liquid branch point is different from the measurement chamber that receives the distribution of the sample liquid from the liquid branch point having a shorter distance between the rotation center and the liquid branch point. The liquid branch whose cross-sectional area of the flow path of the connecting portion is shorter than the distance between the flow center connected to the liquid branch point with the longer distance between the rotation center and the liquid branch point and the rotation center with the liquid branch point. It was made larger than the cross-sectional area of the connection part with the flow path connected to the point to facilitate flow into the measurement chamber 5. This facilitates the flow of the sample liquid into the measurement chamber 5 when the liquid is transferred by centrifugal force, and the amount of the sample liquid introduced into each measurement chamber after being introduced into the measurement chamber 5 before entering the adjacent quantitative unit 9. Is also trying to quantify.

詳しくは、図４〜図６に示すように、ベース基板３１に形成された前記接続部２１に連通した溝形状の誘導毛細管流路１２ａ，１２ｂが、特徴的な手段３４としてカバー基板３２に形成されている。なお、比較例ではこの誘導毛細管流路１２ａ，１２ｂなどが設けられていないために、測定チャンバー５における接続部２１の開口の断面積は、定量部９と定量部１０との接続個所Ｅの開口の断面積と同じであった。   Specifically, as shown in FIGS. 4 to 6, groove-shaped guide capillary channels 12 a and 12 b communicating with the connection portion 21 formed on the base substrate 31 are formed on the cover substrate 32 as characteristic means 34. Has been. In the comparative example, since the guide capillary channels 12a, 12b and the like are not provided, the cross-sectional area of the opening of the connection portion 21 in the measurement chamber 5 is the opening of the connection portion E between the quantitative portion 9 and the quantitative portion 10. The cross-sectional area was the same.

図４は断面積を広く設置した定量部１０と測定チャンバー５の接続部分の拡大斜視図、図５（ａ）（ｂ）は定量部１０と測定チャンバー５のＡ−Ａ，Ｂ−Ｂ接続部分の断面図で、測定チャンバー５の厚み：Ｗ１は３ｍｍ、定量毛細管流路２の厚み：Ｗ２は０．３ｍｍとした。測定チャンバー５の幅：Ｗ３を５ｍｍ、定量毛細管流路２の幅：Ｗ４を２ｍｍとした。また定量部１０と測定チャンバー５の接続部分の断面積を増やすための誘導毛細管流路１２ａ，１２ｂは幅：Ｗ５が１ｍｍ、厚み：Ｗ６は０．５ｍｍとしている。なお、図４は図５（ａ）のＣ−Ｃ断面図である。   4 is an enlarged perspective view of a connecting portion between the quantitative unit 10 and the measurement chamber 5 having a wide cross-sectional area, and FIGS. 5A and 5B are AA and BB connecting portions of the quantitative unit 10 and the measuring chamber 5. FIG. The thickness of the measurement chamber 5: W1 was 3 mm, and the thickness of the quantitative capillary channel 2: W2 was 0.3 mm. The width of the measurement chamber 5: W3 was 5 mm, and the width of the fixed capillary channel 2: W4 was 2 mm. In addition, the guide capillary channels 12a and 12b for increasing the cross-sectional area of the connecting portion between the quantitative unit 10 and the measurement chamber 5 have a width: W5 of 1 mm and a thickness: W6 of 0.5 mm. 4 is a cross-sectional view taken along the line CC of FIG.

また、定量毛細管流路２の幅を設定している面には親水処理を施しておりサンプル液が毛細管力で流れるようにしている。誘導毛細管流路１２ａ，１２ｂについては全ての面に親水処理を施している。ここで各定量部が接続する部分の断面積は、誘導毛細管流路１２ａ，１２ｂのない場合、定量毛細管流路２と各測定チャンバーの接続する部分の断面積と同じであるが、誘導毛細管流路１２ａ，１２ｂを設置した場合には、誘導毛細管流路１２ａ，１２ｂを設置した部分での断面積の方が広くなる。よってサンプル液の表面張力が小さくなり、液を排出し易くなる。ここで各定量部のサンプル液を他流路への進入なく測定チャンバー５内に導入させることができる断面積は、定量部１０と測定チャンバー５の接続部にかかる圧力を他の接続部にかかる圧力より低くすることが出来ればよい。定量部１０と測定チャンバー５の断面にかかる圧力を低くするための最小流路幅および厚みを算出する。拡張に必要な長さＸは、
Ｘ ＝ γ ／ （ ｍ・ｒ・ω２ ／ Ｓ ）
ここで、Ｘ：拡張に必要な長さ、ｍ：分子の質量、ｒ：回転半径、ω：回転数、Ｓ：断面積、γ：表面張力、で定義することができる。 In addition, the surface on which the width of the fixed capillary channel 2 is set is subjected to a hydrophilic treatment so that the sample liquid flows with a capillary force. The guide capillary channels 12a and 12b are all subjected to hydrophilic treatment. Here, the cross-sectional area of the portion to which each quantification unit is connected is the same as the cross-sectional area of the portion to which the quantification capillary channel 2 and each measurement chamber are connected in the absence of the guide capillary channels 12a and 12b. When the paths 12a and 12b are installed, the cross-sectional area at the part where the guide capillary channels 12a and 12b are installed becomes wider. Therefore, the surface tension of the sample liquid is reduced and the liquid can be easily discharged. Here, the cross-sectional area in which the sample solution of each quantification unit can be introduced into the measurement chamber 5 without entering the other flow path is that the pressure applied to the connection part between the quantification unit 10 and the measurement chamber 5 is applied to the other connection part. What is necessary is just to be able to make it lower than a pressure. The minimum flow path width and thickness for reducing the pressure applied to the sections of the quantification unit 10 and the measurement chamber 5 are calculated. The length X required for expansion is
X = γ / (m · r · ω 2 / S)
Here, X: length necessary for expansion, m: mass of molecule, r: rotational radius, ω: rotational speed, S: cross-sectional area, γ: surface tension can be defined.

各接続部にかかる圧力は（ ｍ・ｒ・ω２ ／ Ｓ ）の部分より求めることが出来る。本実施の形態で使用した表面張力は０．０７Ｎ／ｍ、回転半径ｒ＝１５ｍｍ、回転数ω＝４０００ｒｐｍ、流路幅ｗ＝２ｍｍ、流路厚みｔ＝０．３ｍｍとした。ここで誘導毛細管流路１２ａ，１２ｂのない場合における各定量部と各測定チャンバーの接続部の圧力を求めると、およそ４３８３Ｎ／ｍ２となる。よって定量部１０と測定チャンバー５の接続部にかかる圧力をこれより低くすることが出来ればサンプル液を測定チャンバー５へ導入することが出来る。誘導毛細管流路１２ａ，１２ｂの最小流路幅及び厚みは遠心力で回転させた時の圧力で液を排出させることが出来る０．０１７ｍｍ以上を流路幅及び厚みに足した長さ、即ち流路幅なら２．０１７ｍｍ、厚みなら０．３１７ｍｍとする。また最大の流路幅は定量毛細管流路２として設定した２ｍｍとする。これらの形状においてその効果について示す。 The pressure applied to each connecting portion can be obtained from the portion of (m · r · ω 2 / S). The surface tension used in the present embodiment was 0.07 N / m, the rotation radius r = 15 mm, the rotation speed ω = 4000 rpm, the channel width w = 2 mm, and the channel thickness t = 0.3 mm. Here, when the pressure at the connection portion between each quantification unit and each measurement chamber in the case where there is no guide capillary channel 12a, 12b, it is about 4383 N / m 2 . Therefore, if the pressure applied to the connecting portion between the quantification unit 10 and the measurement chamber 5 can be made lower than this, the sample liquid can be introduced into the measurement chamber 5. The minimum flow channel width and thickness of the guide capillary channels 12a and 12b is a length obtained by adding 0.017 mm or more to the flow channel width and thickness so that the liquid can be discharged by the pressure when rotated by centrifugal force. The road width is 2.017 mm, and the thickness is 0.317 mm. The maximum channel width is 2 mm set as the fixed capillary channel 2. The effect of these shapes will be described.

図７に誘導毛細管流路１２ａ，１２ｂを設けた場合の流れパターンについて示す。
図７（ａ）には定量毛細管流路内のサンプル液を遠心力により移送するときの図について示す。図７（ｂ）では遠心力がかかり始めると定量部１０，１１のサンプル液は外周側へ移送され始める。しかし誘導毛細管流路１２ａ，１２ｂが設けられているため、定量部１０と測定チャンバー５の接続部に働く表面張力は弱くなり、低い回転数の時でも測定チャンバー５内に導入させることができる。図７（ｃ）を見ると、測定チャンバー５に移送されたサンプル液の量は測定チャンバー６と同じ量が確保されていることが確認できる。このことから測定チャンバー５と定量毛細管流路２との接続部に誘導毛細管流路１２ａ，１２ｂを設置し、断面積を増やすことで遠心力が表面張力より大きければサンプル液は測定チャンバー内に導入され易くなって、測定チャンバー３と測定チャンバー４とのサンプル液の液量のばらつきが低減され、測定チャンバー５と測定チャンバー６とのサンプル液の液量のばらつきが低減されることを確認した。 FIG. 7 shows a flow pattern when the guide capillary channels 12a and 12b are provided.
FIG. 7A shows a diagram when the sample liquid in the quantitative capillary channel is transferred by centrifugal force. In FIG. 7B, when the centrifugal force starts to be applied, the sample liquid in the quantification units 10 and 11 starts to be transferred to the outer peripheral side. However, since the guide capillary channels 12a and 12b are provided, the surface tension acting on the connecting portion between the quantification unit 10 and the measurement chamber 5 becomes weak and can be introduced into the measurement chamber 5 even at a low rotational speed. 7C, it can be confirmed that the same amount of the sample liquid transferred to the measurement chamber 5 as that of the measurement chamber 6 is secured. For this reason, if the centrifugal force is larger than the surface tension by installing guide capillary channels 12a and 12b at the connection between the measurement chamber 5 and the fixed capillary channel 2 and increasing the cross-sectional area, the sample solution is introduced into the measurement chamber. As a result, it was confirmed that the variation in the amount of sample liquid between the measurement chamber 3 and the measurement chamber 4 was reduced, and the variation in the amount of sample liquid between the measurement chamber 5 and the measurement chamber 6 was reduced.

以上のことより、定量部１０と測定チャンバー５の接続部の断面積を、定量部同士が接続する部分の断面積より広く設定することで、圧力を下げ測定チャンバー５内に流入させ易くすると各定量部で定量されたサンプル液を測定チャンバーに移送させることが出来る。   From the above, by setting the cross-sectional area of the connection portion between the quantification unit 10 and the measurement chamber 5 wider than the cross-sectional area of the portion where the quantification units are connected to each other, it is possible to reduce the pressure and easily flow into the measurement chamber 5. The sample liquid quantified by the quantification unit can be transferred to the measurement chamber.

なお、上記の実施の形態では拡張に必要な長さ：Ｘを、定量部と定量部の接続部の流路厚みに足した場合を説明したが、定量部と定量部の接続部の流路の幅に拡張に必要な長さ：Ｘを足して実施することもできる。   In the above embodiment, the case where the length required for expansion: X is added to the channel thickness of the connecting portion between the quantifying unit and the quantifying unit has been described. It is also possible to carry out by adding the length required for expansion to the width: X.

本発明は、定量デバイスを使用して測定チャンバーにおけるサンプル液と試薬との混合物に電気的または光学的にアクセスして、生物学的流体の成分測定する各種の分析装置の分析精度の向上に寄与できる。   The present invention contributes to improving the analysis accuracy of various analyzers that measure components of biological fluids by electrically or optically accessing a mixture of sample liquid and reagent in a measurement chamber using a quantitative device. it can.

本発明の実施の形態における定量デバイスのベース基板の上面図Top view of a base substrate of a quantitative device in an embodiment of the present invention 同実施の形態における定量デバイスの側面図Side view of the quantitative device in the same embodiment 同実施の形態における定量毛細管流路における定量部の説明図Explanatory drawing of the fixed_quantity | quantitative_assay part in the fixed_quantity | capacitance capillary channel in the same embodiment 定量部１０と測定チャンバー５の接続部分の断面の拡大斜視図An enlarged perspective view of a cross section of a connecting portion between the quantification unit 10 and the measurement chamber 5 定量部１０と測定チャンバー５のＡ−Ａ，Ｂ−Ｂ接続部分の断面図Sectional drawing of AA and BB connection part of fixed_quantity | quantitative_assay part 10 and measurement chamber 5 同実施の形態における誘導毛細管流路の拡大斜視図Enlarged perspective view of the guide capillary channel in the same embodiment 同実施の形態における流れパターン図Flow pattern diagram in the same embodiment 比較例における定量デバイスのベース基板の上面図Top view of the base substrate of the quantitative device in the comparative example 同比較例における流れパターン図Flow pattern diagram in the comparative example 従来例の遠心移送式バイオセンサーの試料液分配構成を説明するための図The figure for demonstrating the sample liquid distribution structure of the centrifugal transfer type biosensor of a prior art example

符号の説明Explanation of symbols

１ 充填用チャンバー
２ 定量毛細管流路
３，４，５，６ 測定チャンバー
７ 廃棄用チャンバー
８，９，１０，１１ 定量部
１２ａ，１２ｂ 誘導毛細管流路
１３ 回転中心
１４，１５，１６，１７，１８ 液分岐点
１９，２０，２１，２２ 接続部
２３ 接続部
２４，２５ 空気穴チャンバー
３１ ベース基板
３２ カバー基板
３３ａ，３３ｂ，３３ｃ，３３ｄ，３３ｅ，３３ｆ，３３ｇ，３３ｈ 孔
Ｅ 定量部９と定量部１０との接続個所 DESCRIPTION OF SYMBOLS 1 Filling chamber 2 Fixed capillary flow path 3, 4, 5, 6 Measurement chamber 7 Disposal chamber 8, 9, 10, 11 Fixed_quantity | quantitative_assay part 12a, 12b Guide capillary flow path 13 Rotation center 14, 15, 16, 17, 18 Liquid branch point 19, 20, 21, 22 Connection portion 23 Connection portion 24, 25 Air hole chamber 31 Base substrate 32 Cover substrate 33a, 33b, 33c, 33d, 33e, 33f, 33g, 33h Hole E Determination portion 9 and determination portion Connection point with 10

Claims (3)

充填用チャンバーのサンプル液を複数の測定チャンバーに分配するために回転中心の回りに回転させて使用する定量デバイスであって、
前記回転中心に対して前記複数の測定チャンバーを外周側に沿って配置し、
基端が前記充填用チャンバーに接続され蛇行しながら前記回転中心と前記複数の測定チャンバーの間を周方向に延長され内周側の変曲点を液分岐点として前記複数の測定チャンバーにサンプル液を分配する接続部を有する定量毛細管流路を設け、
前記回転中心と液分岐点との距離が異なる部分では、前記回転中心と液分岐点との距離が短い方の液分岐点からサンプル液の分配を受ける測定チャンバーとの接続部の流路の断面積が、前記回転中心と液分岐点との距離が長い方の液分岐点に接続された流路と前記回転中心と液分岐点との距離が短い方の液分岐点に接続された流路との接続部の断面積よりも大きい
定量デバイス。 A quantitative device that is used by rotating around a rotation center to distribute a sample liquid in a filling chamber to a plurality of measurement chambers,
The plurality of measurement chambers are arranged along the outer peripheral side with respect to the rotation center,
The base end is connected to the filling chamber and meanderingly extends between the rotation center and the plurality of measurement chambers in the circumferential direction, and an inflection point on the inner peripheral side is set as a liquid branch point to the plurality of measurement chambers. Providing a metered capillary channel with connections to distribute
In the part where the distance between the rotation center and the liquid branch point is different, the flow path of the connection part with the measurement chamber receiving the distribution of the sample liquid from the liquid branch point with the shorter distance between the rotation center and the liquid branch point is cut off. A flow path connected to a liquid branch point where the distance between the rotation center and the liquid branch point is longer, and a flow path connected to a liquid branch point where the distance between the rotation center and the liquid branch point is shorter Quantitative device larger than the cross-sectional area of the connection part. 前記定量部と前記チャンバーの接続部の面積は、
Ｘ ＝ γ ／ （ ｍ・ｒ・ω２ ／ Ｓ ）
Ｘ：拡張に必要な長さ、ｍ：分子の質量、ｒ：回転半径、ω：回転数、Ｓ：断面積、γ：表面張力、で示される長さを、前記定量部と定量部の接続部の流路幅もしくは厚みに足した長さで表されることを特徴とする
請求項１に記載の定量デバイス。 The area of the connecting portion between the quantitative unit and the chamber is:
X = γ / (m · r · ω 2 / S)
X: Length required for expansion, m: molecular mass, r: radius of rotation, ω: rotational speed, S: cross-sectional area, γ: surface tension The quantitative device according to claim 1, wherein the quantitative device is represented by a length added to a flow path width or a thickness of the portion. 流路および測定チャンバーの壁面には親水処理が施されていることを特徴とする
請求項１に記載の定量デバイス。 The quantitative device according to claim 1, wherein the flow path and the wall surface of the measurement chamber are subjected to hydrophilic treatment.
JP2008076911A 2007-11-08 2008-03-25 Quantitative device Active JP5268402B2 (en)

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Application Number Priority Date Filing Date Title
JP2008076911A JP5268402B2 (en) 2008-03-25 2008-03-25 Quantitative device
CN2008801077592A CN101802622B (en) 2007-11-08 2008-11-07 Analyzing device and analyzing method using same
CN201310443484.2A CN103487596B (en) 2007-11-08 2008-11-07 Analyzing method using analyzing device
US12/741,929 US9182384B2 (en) 2007-11-08 2008-11-07 Analyzing device and analyzing method using same
EP08848318.5A EP2219034B1 (en) 2007-11-08 2008-11-07 Analyzing device and analyzing method using same
CN201310443482.3A CN103499702B (en) 2007-11-08 2008-11-07 Analyzing device
PCT/JP2008/003222 WO2009060617A1 (en) 2007-11-08 2008-11-07 Analyzing device and analyzing method using same
US14/877,663 US10101317B2 (en) 2007-11-08 2015-10-07 Rotatable analyzing device with a separating cavity and a capillary cavity

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