JP2006071388A - Microchip and fluid control method in microchip - Google Patents

Microchip and fluid control method in microchip Download PDF

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JP2006071388A
JP2006071388A JP2004253671A JP2004253671A JP2006071388A JP 2006071388 A JP2006071388 A JP 2006071388A JP 2004253671 A JP2004253671 A JP 2004253671A JP 2004253671 A JP2004253671 A JP 2004253671A JP 2006071388 A JP2006071388 A JP 2006071388A
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flow
flow path
inflow side
microchip
sample liquid
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Kazuhiro Miyamura
和宏 宮村
Takehiko Kitamori
武彦 北森
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Horiba Ltd
Kanagawa Academy of Science and Technology
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Kanagawa Academy of Science and Technology
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a microchip and a fluid control method in the microchip capable of generating a three-dimensional flow and converging surely a sample flow by using an easy constitution without using an external force such as an electric field, a magnetic field or an ultrasonic wave or a complicated fluid control mechanism. <P>SOLUTION: This microchip is equipped with a passage 83 on the inflow side, a passage 84 on the outflow side, and a sample liquid introduction path 87a and sheath liquid introduction paths 83a, 83b provided so as to join to the upstream side of the passage 83 on the inflow side, and a sample liquid flow S is sandwiched by sheath liquid flows F<SB>1</SB>, F<SB>2</SB>. In the microchip, a step part 2 for converging the sample liquid flow S sandwiched by the sheath liquid flows F<SB>1</SB>, F<SB>2</SB>is provided on the passage 83 on the inflow side. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

この発明は、マイクロチップおよびマイクロチップ中における流体制御方法に関するものである。 The present invention relates to a microchip and a fluid control method in the microchip.

従来から、例えば粒度分布を測定したり、粒子量を計測したり、あるいは、血液中の赤血球、白血球、血小板などの血球を計数する手法の一つとして電気抵抗法（コールター法）が知られている。この電気抵抗法は、例えば血球を計数する場合、血液細胞を等張性希釈液に懸濁させ、粒子が絞り部を通過するときに、血球が占める容積に比例した電気抵抗（インピーダンス）の変化が生じ、このインピーダンス変化に対応して生ずるパルス数を計数することにより、血球の個数を検出することができ、また、前記パルスの高さを検出することにより、血球の容積（白血球、赤血球、血小板であるかの種類）を検出することができる。   Conventionally, for example, the electrical resistance method (Coulter method) is known as a method for measuring particle size distribution, measuring the amount of particles, or counting blood cells such as red blood cells, white blood cells, and platelets in blood. Yes. In this electrical resistance method, for example, when counting blood cells, changes in electrical resistance (impedance) proportional to the volume occupied by blood cells when the blood cells are suspended in an isotonic diluent and the particles pass through the constriction. By counting the number of pulses generated in response to this impedance change, the number of blood cells can be detected, and by detecting the height of the pulse, the volume of blood cells (white blood cells, red blood cells, The type of platelet).

ところで、近年においては、電気抵抗法のマイクロ化が進められており、前記電気抵抗法に則ったチップ状のマイクロコールターカウンタが開発されるに至っている。そのマイクロコールターカウンタの測定部では、例えばシリコン基板に測定対象である微粒子が混入したサンプル液が流れる流入側の流路および流出側の流路と、これら流路の途中に形成される絞り部と、前記流入側の流路および流出側の流路にそれぞれ設けられる電極とが備えられている。   By the way, in recent years, the electric resistance method has been miniaturized, and a chip-shaped micro coulter counter conforming to the electric resistance method has been developed. In the measurement unit of the micro coulter counter, for example, an inflow channel and an outflow channel through which a sample liquid in which fine particles to be measured are mixed in a silicon substrate, and a throttle unit formed in the middle of these channels, And an electrode provided in each of the inflow side flow path and the outflow side flow path.

図１２は従来のこの種マイクロコールターカウンタにおける測定部のマイクロチップ構成を示す上面図である。図１２において、８０はシリコン基板で、例えば厚さが５００μｍ、長さが１０ｍｍ、幅が５ｍｍ程度の大きさに形成されている。８１はシリコン基板８０の上面に形成される流路で、例えば、ＭＥＭＳ（マイクロ・エレクトロ・メカニカル・システムズ）プロセスや、マイクロマシニングや、エッチング、あるいは光造型などによる加工技術を用いて形成される適宜の深さａ〔図１３（Ｂ）および図１３（Ｃ）参照〕の溝よりなる。前記光造型とは、光線を照射すると硬化する樹脂に紫外線レーザを当てて成形する方法である。なお、図１３（Ａ）は、図１２から後述する電極８５，８６、電極リード部９０，９１、信号端子９２，９３を除いたものを示し、図１３（Ｂ）、図１３（Ｃ）および図１３（Ｄ）は流路測定部のチップ断面図を示し、それぞれ、図１３（Ａ）におけるＸ−Ｘ´線断面図、Ｙ−Ｙ´線断面図およびＺ−Ｚ´線断面図を示す。   FIG. 12 is a top view showing a microchip configuration of a measuring section in a conventional micro Coulter counter of this type. In FIG. 12, reference numeral 80 denotes a silicon substrate, which has a thickness of about 500 μm, a length of 10 mm, and a width of about 5 mm. Reference numeral 81 denotes a flow path formed on the upper surface of the silicon substrate 80. For example, the flow path is appropriately formed by using a processing technique such as a MEMS (micro electro mechanical systems) process, micro machining, etching, or photo molding. And a groove having a depth a (see FIGS. 13B and 13C). The photomolding is a method in which an ultraviolet laser is applied to a resin that cures when irradiated with light. FIG. 13A shows a configuration obtained by removing electrodes 85 and 86, electrode lead portions 90 and 91, and signal terminals 92 and 93, which will be described later, from FIG. 12, and FIG. 13B, FIG. FIG. 13D shows a chip cross-sectional view of the flow path measuring unit, and shows a cross-sectional view taken along line XX ′, a cross-sectional view taken along line YY ′, and a cross-sectional view taken along line ZZ ′ in FIG. .

この流路８１は、絞り部８２とこの絞り部８２の上流側に形成される流入側の流路８３と、絞り部８２の下流側に形成される流出側の流路８４とから主としてなる。絞り部８２は、流路８１のほぼ中間において流路幅が一定長さの例えば１０〜６０μｍと狭くなるよう形成され、流路８３，８４は、例えば１００〜１０００μｍと比較的幅広の一定長さの流路幅を有する。流路８３，８４の断面は図１３（Ｂ）、図１３（Ｃ）および図１３（Ｄ）に示すように例えば逆台形形状をなしており、深さ（高さ）ａが例えば４０μｍ、下底の幅ｂが例えば５００μｍ、上底の幅ｃが例えば５１０μｍである。また、絞り部８２の断面も例えば逆台形形状をなしており、深さ（高さ）が例えば４０μｍ、下底の幅が例えば５０μｍ、上底の幅が例えば６０μｍである。そして、前記流路８１などを覆うようにしてシリコン基板８０上に例えば陽極接合などの手法で例えば透明なガラス板（閉塞部）Ｇが接合されている。このガラス板Ｇはシリコン基板８０と同じ寸法を有し、ガラス板Ｇがシリコン基板８０に接合されることにより、流路８１の各部である流入側の流路８３と絞り部８２と流出側の流路８４は、外部と遮断された状態で閉塞される。８５は流入側の流路８３におけるガラス板底面に形成される電極であり、８６は流出側の流路８４におけるガラス板底面に形成される電極である。これらの電極８５，８６はサンプル液８７が絞り部８２を通過するときに生ずるインピーダンス変化を検出するためのものである。８８，８９は、例えば血球を計数する場合、例えば生理食塩水などの液体（以下、シース液という）で、サンプル液８７を挟む形で流路８３に導入される。８３ａ，８３ｂは流路８３の上流側に設けたシース液導入路で流路８３に連通するようシリコン基板８０の上面に形成される。８７ａは、流路８３の上流側に設けたサンプル液導入路で流路８３に連通するようシリコン基板８０の上面に形成される。なお、シリコン基板８０以外に、アクリル樹脂、ＰＥＴ樹脂、ポリスチレン樹脂、エポキシ樹脂、ガラスなどが基板の材料として適用可能である。   The flow path 81 mainly includes a throttle section 82, an inflow side flow path 83 formed on the upstream side of the throttle section 82, and an outflow side flow path 84 formed on the downstream side of the throttle section 82. The narrowing portion 82 is formed so that the flow path width becomes narrow at a certain length, for example, 10 to 60 μm, approximately in the middle of the flow path 81, and the flow paths 83 and 84 have a relatively wide constant length, for example, 100 to 1000 μm. The flow path width is as follows. The cross sections of the flow paths 83 and 84 have, for example, an inverted trapezoidal shape as shown in FIGS. 13 (B), 13 (C), and 13 (D), and the depth (height) is 40 μm, for example. The bottom width b is, for example, 500 μm, and the top width c is, for example, 510 μm. In addition, the section of the diaphragm 82 has, for example, an inverted trapezoidal shape, and the depth (height) is, for example, 40 μm, the width of the lower base is, for example, 50 μm, and the width of the upper base is, for example, 60 μm. For example, a transparent glass plate (blocking portion) G is bonded onto the silicon substrate 80 by a technique such as anodic bonding so as to cover the flow path 81 and the like. The glass plate G has the same dimensions as the silicon substrate 80, and the glass plate G is bonded to the silicon substrate 80, whereby the inflow side flow channel 83, the throttle unit 82, and the outflow side of the flow channel 81. The flow path 84 is closed in a state of being blocked from the outside. Reference numeral 85 denotes an electrode formed on the bottom surface of the glass plate in the flow channel 83 on the inflow side, and reference numeral 86 denotes an electrode formed on the bottom surface of the glass plate in the flow channel 84 on the outflow side. These electrodes 85 and 86 are for detecting a change in impedance that occurs when the sample liquid 87 passes through the throttle portion 82. For example, when counting blood cells, 88 and 89 are introduced into the flow path 83 in a form that sandwiches the sample liquid 87 with a liquid such as physiological saline (hereinafter referred to as a sheath liquid). 83 a and 83 b are formed on the upper surface of the silicon substrate 80 so as to communicate with the flow path 83 through a sheath liquid introduction path provided on the upstream side of the flow path 83. 87 a is formed on the upper surface of the silicon substrate 80 so as to communicate with the flow path 83 through a sample solution introduction path provided on the upstream side of the flow path 83. In addition to the silicon substrate 80, an acrylic resin, a PET resin, a polystyrene resin, an epoxy resin, glass, or the like can be used as a substrate material.

すなわち、流路８１の上流の導入側においては、流路８１の上流側からみてサンプル液導入路８７ａの左右にシース液導入路８３ａ，８３ｂが位置しており、サンプル液導入路８７ａを右側のシース液導入路８３ａと左側のシース液導入路８３ｂで挟むように合流させ、この合流流路を流入側の流路８３としている。９４は前記導入路８３ａ，８３ｂ，８７ａの合流位置を示す。   That is, on the introduction side upstream of the flow path 81, the sheath liquid introduction paths 83 a and 83 b are located on the left and right of the sample liquid introduction path 87 a when viewed from the upstream side of the flow path 81, and the sample liquid introduction path 87 a is located on the right side. The flow is merged so as to be sandwiched between the sheath liquid introduction path 83a and the left sheath liquid introduction path 83b, and this merge flow path is used as the flow path 83 on the inflow side. Reference numeral 94 denotes a joining position of the introduction paths 83a, 83b, 87a.

９０および９１は電極８５および８６にそれぞれ連なる電極リード部である。９２および９３は、サンプル液８７の測定時に、マイクロコールターカウンタの計器本体（図示せず）に接続するための信号端子であり、これらの信号端子９２，９３は電極リード部９０，９１にそれぞれ接続される。   Reference numerals 90 and 91 denote electrode lead portions connected to the electrodes 85 and 86, respectively. Reference numerals 92 and 93 are signal terminals for connection to the instrument body (not shown) of the micro Coulter counter when measuring the sample solution 87. These signal terminals 92 and 93 are connected to the electrode lead portions 90 and 91, respectively. Is done.

なお、Ｓはサンプル液８７の流れ（サンプル流）を示し、Ｆ1 ，Ｆ2 はシース液の流れ（シース流）を示す。 S indicates the flow of the sample liquid 87 (sample flow), and F 1 and F 2 indicate the flow of the sheath liquid (sheath flow).

上記構成のマイクロコールターカウンタにおける測定部のマイクロチップにおいて、サンプル液８７の測定を行う場合、流入側の流路８３の最上流側である合流位置９４においてサンプル液８７をシース液８８，８９で挟み込むように合流させ、この状態で、サンプル液８７が流入側の流路８３に導入される。流路８３を流れるサンプル液８７は、幅ｅがμｍオーダーのため層流状態であり、乱流ではない。そして、サンプル液８７が流入側の流路８３から絞り部８２を流れ、流出側の流路８４に導かれ、サンプル流出口９５から排出される。ここで、サンプル液８７が絞り部８２を流れるとき、電極８５と電極８６間のインピーダンスが変化し、このインピーダンスの変化を示す検出信号が電極リード部９０，９１を介して信号端子９２，９３から取り出され、計器本体（図示せず）に入力され、計器本体において所定の演算が行われることによって、例えば粒度分布を測定したり、粒子量を計測したり、あるいは、血液中の赤血球、白血球、血小板などの血球が計数される。   When the sample liquid 87 is measured in the microchip of the measurement unit in the micro coulter counter having the above-described configuration, the sample liquid 87 is sandwiched between the sheath liquids 88 and 89 at the joining position 94 that is the most upstream side of the flow path 83 on the inflow side. In this state, the sample solution 87 is introduced into the flow channel 83 on the inflow side. The sample solution 87 flowing through the flow channel 83 is in a laminar flow state because the width e is on the order of μm, and is not turbulent. Then, the sample liquid 87 flows from the flow path 83 on the inflow side through the throttle portion 82, is guided to the flow path 84 on the outflow side, and is discharged from the sample outlet 95. Here, when the sample liquid 87 flows through the throttle portion 82, the impedance between the electrode 85 and the electrode 86 changes, and a detection signal indicating the change in impedance is transmitted from the signal terminals 92 and 93 via the electrode lead portions 90 and 91. It is taken out and input to the instrument body (not shown), and a predetermined calculation is performed in the instrument body. For example, the particle size distribution is measured, the amount of particles is measured, or red blood cells, white blood cells, Blood cells such as platelets are counted.

ここで、前記検出信号のＳ／Ｎ比を向上させるには、サンプル液８７が絞り部８２に来るまでにシース液８８，８９によって挟まれるサンプル液８７の領域を、少なくとも深さ方向〔図１３（Ｂ）および図１３（Ｃ）における両矢印Ｄで示す方向〕においてできるだけ収束させるのが好ましいけれども、上記構成のマイクロコールターカウンタにおける測定部のマイクロチップにおいては難しかった。   Here, in order to improve the S / N ratio of the detection signal, at least the depth direction of the region of the sample liquid 87 sandwiched between the sheath liquids 88 and 89 before the sample liquid 87 reaches the throttle portion 82 [FIG. (B) and the direction indicated by the double-headed arrow D in FIG. 13C] are preferably converged as much as possible, but are difficult in the microchip of the measurement unit in the micro-coulter counter having the above configuration.

例えば、レーザ光の散乱を利用したパーティクルカウンタに用いられ、サンプル流を一点に集中させて検出信号のＳ／Ｎ比を向上させるための構造として、従来から図１４に示すようなシースフロー構造が一般的である。図１４において、前記シースフロー構造は、パイプ９６，９７を２重にし、外側のパイプ９６よりシース液、内側のパイプ９７のノズル部分よりサンプル液を流すことによりサンプル液の流れがシース液に囲まれてなる層流が発生するとともに、この流れを絞り部９８で絞り込むことによって流れの中にサンプル液を収束でき、この状態でレーザ光が照射されるものである。   For example, a sheath flow structure as shown in FIG. 14 has been conventionally used as a structure for improving the S / N ratio of a detection signal by concentrating a sample flow at one point and used in a particle counter using laser light scattering. It is common. In FIG. 14, the sheath flow structure has pipes 96, 97 doubled, the sheath liquid is surrounded by the sheath liquid by flowing the sheath liquid from the outer pipe 96 and the sample liquid from the nozzle portion of the inner pipe 97. As a result, a laminar flow is generated, and the flow is narrowed by the narrowing portion 98, so that the sample liquid can be converged in the flow, and the laser beam is irradiated in this state.

しかし、上記構成のマイクロコールターカウンタではマイクロチップの特性上マイクロチップ中において前記シースフロー構造のような３次元構造を作成することが難しく、図１２に示したような２次元的な構造を採用せざるを得なかった。   However, in the micro Coulter counter configured as described above, it is difficult to create a three-dimensional structure such as the sheath flow structure in the microchip due to the characteristics of the microchip, and a two-dimensional structure as shown in FIG. I had to.

そのため、上記構成のマイクロコールターカウンタにおける測定部のマイクロチップにおいて、サンプル液８７は、サンプル流Ｓの少なくともＤ方向における流路断面形状が図１３（Ｂ）で示す合流位置９４での略矩形１００のまま高さａが絞られることなく図１３（Ｃ）で示すような状態で流入側の流路８３を流れることになり、この流路８３を流れるサンプル液８７の流れＳ1 を、流路８１の幅方向〔図１３における両矢印Ｗで示す方向；Ｄ方向に直交する方向〕における流路断面形状が幅ｅよりも小さな例えば１〜１０μｍの幅ｂ’〔図１３（Ｄ）参照〕になるよう絞り部８２において絞れても、Ｄ方向には絞り込むことはできなかった。結果として、流入側の流路８３の流れＳ1 を絞りきれず、検出信号のＳ／Ｎ比を向上させるのが難しかった。 Therefore, in the microchip of the measurement unit in the micro Coulter counter having the above-described configuration, the sample liquid 87 has a substantially rectangular shape 100 at the merging position 94 shown in FIG. As shown in FIG. 13C, the height a is not reduced, and the inflow side flow path 83 flows, and the flow S 1 of the sample liquid 87 flowing through the flow path 83 is changed into the flow path 81. The cross-sectional shape of the flow path in the width direction [the direction indicated by the double arrow W in FIG. 13; the direction perpendicular to the D direction] is a width b ′ of 1 to 10 μm, for example, smaller than the width e (see FIG. 13D). Even if the aperture portion 82 was narrowed, it could not be narrowed in the D direction. As a result, it is difficult to improve the S / N ratio of the detection signal because the flow S 1 of the flow channel 83 on the inflow side cannot be fully throttled.

これを解消するために、図１５〜図１７に示すごとくマイクロチップ中において流れを制御できる方法が考えられるが、複雑な流体制御機構を用いたり、電界、磁界、超音波の他の外力を用いることによって流れを変えるようにしなければならないといった欠点があった。   In order to solve this problem, a method that can control the flow in the microchip as shown in FIGS. 15 to 17 can be considered. However, a complicated fluid control mechanism is used, or an electric field, a magnetic field, or other external force of ultrasonic waves is used. There was a disadvantage that the flow had to be changed depending on the situation.

図１５に示すマイクロチップは、導入路８３ａ，８３ｂ，８７ａの合流位置９４の下流に設けた流入側の流路８３における底部に導入孔１０１を介して三つ目のシース液導入路８３ｃを連通させ、導入孔１０１から導入するシース流Ｆ3 によってサンプル流Ｓを上部に押し上げるように構成されている。しかし、マイクロチップに導入孔１０１を形成する加工上の問題とシース流Ｆ1 ，Ｆ2 ，Ｆ3 やサンプル流Ｓを制御する上での複雑な流体制御上の問題がある。 The microchip shown in FIG. 15 communicates with the third sheath liquid introduction path 83c through the introduction hole 101 at the bottom of the inflow side flow path 83 provided downstream of the joining position 94 of the introduction paths 83a, 83b, 87a. The sample flow S is pushed upward by the sheath flow F 3 introduced from the introduction hole 101. However, there are problems in processing to form the introduction hole 101 in the microchip and complicated fluid control problems in controlling the sheath flows F 1 , F 2 , F 3 and the sample flow S.

図１６に示すマイクロチップは、流入側の流路８３に電極１０２あるいは磁界発生手段を形成し、電界あるいは磁界を印加することにより、微粒子を中央部に引き寄せるように制御する構成を有しているが、電界あるいは磁界の影響を受けない流体中の微粒子で構成されるサンプル液には用いることはできない。   The microchip shown in FIG. 16 has a configuration in which the electrode 102 or the magnetic field generating means is formed in the flow channel 83 on the inflow side, and the fine particles are controlled to be drawn toward the center by applying an electric field or a magnetic field. However, it cannot be used for a sample liquid composed of fine particles in a fluid that is not affected by an electric field or a magnetic field.

図１７に示すマイクロチップは、超音波振動子１０３を設け、その周波数をコントロールすることにより共振させて発生する波のノードに流体中の微粒子を集めるように構成されているが、超音波振動子１０３を用いなければならないという問題点がある。   The microchip shown in FIG. 17 includes an ultrasonic vibrator 103 and is configured to collect fine particles in a fluid at a wave node generated by resonating by controlling the frequency of the ultrasonic vibrator 103. There is a problem that 103 must be used.

また、外部から供給した複数種類の微量な液体を混合して取り出すマイクロミキサ（マイクロチップ）において、混合流路に沿ってその底面側には流路を横切る方向に延在する複数条の凸条絞り部を形成すること、すなわち、混合流路に沿って局部的に流路断面を狭める複数の絞り部を直列に並べて形成するようにしたものが下記特許文献１に提案されている。
特開２００２−３４６３５５ Further, in a micromixer (microchip) that mixes and takes out a plurality of kinds of minute amounts of liquid supplied from the outside, a plurality of ridges extending in a direction crossing the flow path on the bottom surface side along the mixing flow path The following Patent Document 1 proposes forming a throttle portion, that is, forming a plurality of throttle portions that locally narrow the cross-section of the flow path along the mixing flow path.
JP 2002-346355 A

しかし、上記文献には、混合流路が狭められる部分を有することが記載されているだけで、試料液の流れが試薬液に囲まれてなる層流が発生するとともに、この流れを絞り部で絞り込むことによって流れの中に試料液を収束させるという技術思想はない。   However, the above document only describes that the mixing channel has a narrowed portion, and a laminar flow in which the flow of the sample solution is surrounded by the reagent solution is generated, and this flow is There is no technical idea of converging the sample liquid in the flow by narrowing down.

この発明は、上述の事柄に留意してなされたもので、その目的は、電界、磁界、超音波の他の外力や複雑な流体制御機構を用いることなく容易な構成を用いることにより３次元的な流れを作りだしてサンプル流を確実に収束させることができるマイクロチップおよびマイクロチップ中における流体制御方法を提供することである。   The present invention has been made in consideration of the above-mentioned matters, and its object is to provide a three-dimensional structure by using an easy configuration without using an electric field, a magnetic field, other external forces of ultrasonic waves, or a complicated fluid control mechanism. It is to provide a microchip and a fluid control method in the microchip that can create a simple flow and reliably converge the sample flow.

上記目的を達成するために、この発明のマイクロチップは、流入側の流路と、流出側の流路と、流入側の流路の上流側に合流するよう設けたサンプル液導入路およびシース液導入路とを備え、サンプル液の流れをシース液の流れによって挟み込むようにしてあるマイクロチップにおいて、シース液の流れで挟み込まれたサンプル液の流れを収束させる段差部を流入側の流路に設けてあることを特徴とする（請求項１）。   In order to achieve the above object, a microchip according to the present invention includes a sample liquid introduction path and a sheath liquid provided so as to join the upstream side of the inflow side flow path, the outflow side flow path, and the inflow side flow path. In a microchip provided with an introduction channel and configured to sandwich the flow of the sample liquid by the flow of the sheath liquid, a step portion for converging the flow of the sample liquid sandwiched by the flow of the sheath liquid is provided in the flow path on the inflow side. (Claim 1).

また、この発明は別の観点から、サンプル液導入路およびシース液導入路をこれらの下流に設けた流入側の流路に合流させてサンプル液の流れをシース液の流れによって挟み込み、さらに、シース液の流れで挟み込まれたサンプル液の流れを、流入側の流路に設けた段差部によって収束させるようにしたことを特徴とするマイクロチップ中における流体制御方法を提供する（請求項８）。   Further, according to another aspect of the present invention, the sample liquid introduction path and the sheath liquid introduction path are joined to an inflow side flow path provided downstream thereof, and the flow of the sample liquid is sandwiched by the flow of the sheath liquid. A fluid control method in a microchip is provided, wherein the flow of the sample liquid sandwiched between the liquid flows is converged by a step portion provided in the flow path on the inflow side (Claim 8).

この発明のマイクロチップ（請求項１，８）では、段差部を例えば図３，４に示すようにサンプル液導入路およびシース液導入路が合流する流入側の流路における下面側に設ける場合、段差部により、サンプル液の流れは上部に押し上げられる（図３）とともに、両サイドのシース液は段差部の上流側側面によって段差部の中央に流れを変更されるため（図４）、さらにサンプル液の流れを押し上げる作用が生じ、段差部を通過したサンプル液は、流路断面形状が図２（Ｂ）で示す合流位置での幅および高さのままではなく、図２（Ｃ）で示すように少なくとも高さが絞られて小さくなった、いわゆる、収束状態で流入側の流路を流れることになる。   In the microchip of the present invention (Claims 1 and 8), when the stepped portion is provided on the lower surface side in the flow path on the inflow side where the sample liquid introduction path and the sheath liquid introduction path merge as shown in FIGS. The flow of the sample liquid is pushed upward by the step portion (FIG. 3), and the flow of the sheath liquid on both sides is changed to the center of the step portion by the upstream side surface of the step portion (FIG. 4). The action of pushing up the flow of the liquid is generated, and the sample liquid that has passed through the stepped portion is not shown in FIG. 2 (C), but in the cross-sectional shape of the flow path as shown in FIG. 2 (B). Thus, at least the height is reduced and the flow becomes smaller in a so-called converged state, and flows in the flow path on the inflow side.

そして、この状態で流入側の流路を通過したサンプル液は、流入側の流路と流出側の流路との間に設けた絞り部を流れるときに高さがさらに絞られて小さくなる。すなわち、絞り部において、サンプル液は流路の中央上部へ収束される。そのため、サンプル液が絞り部を流れるとき、得られる検出信号、例えば電極と電極間のインピーダンスの変化を示す検出信号や、例えばレーザ光散乱によって得られる検出信号のＳ／Ｎ比を向上させることができる。   Then, the sample liquid that has passed through the inflow side flow path in this state is further reduced in height when it flows through a constriction provided between the inflow side flow path and the outflow side flow path. That is, the sample solution is converged to the upper center of the flow path at the throttle portion. Therefore, it is possible to improve the S / N ratio of the detection signal obtained when the sample liquid flows through the throttle portion, for example, the detection signal indicating a change in impedance between the electrodes or the detection signal obtained by, for example, laser light scattering. it can.

要するに、例えば平面視Ｖ型形状の段差部を、流入側の流路の溝の底面から凸状に突出してなる上向き突起によって形成した場合、中央のサンプル液の流れは段差部により持ち上げられる。一方、外側のシース液の流れも段差部により持ち上げられるが、このシース液の流れの方向は段差部と直交する方向に変化する。つまり、平面視Ｖ型形状の段差部の場合は流路外側にシース液の流れがシフトする。その結果、流路外側のシース液の流速が速くなり、中央のサンプル液の流れは上方に持ち上げられた後、流路外側のシース液の流速が速いためサンプル液の流れは相対的に収束する。   In short, for example, when a stepped portion having a V shape in plan view is formed by an upward projection protruding in a convex shape from the bottom surface of the groove on the inflow side, the flow of the central sample liquid is lifted by the stepped portion. On the other hand, the flow of the outer sheath liquid is also lifted by the step portion, but the direction of the flow of the sheath liquid changes in a direction orthogonal to the step portion. That is, in the case of a stepped portion having a V shape in plan view, the flow of the sheath liquid shifts to the outside of the flow path. As a result, the flow rate of the sheath liquid outside the flow path is increased, the flow of the sample liquid at the center is lifted upward, and the flow rate of the sheath liquid outside the flow path is high, so the flow of the sample liquid is relatively converged. .

また、例えば平面視Ｖ型形状の段差部を、流入側の流路の溝の底面を凹ませてなる下向き凹所によって形成した場合、流路外側のシース液の流れは段差部に入ると段差部壁面に当たることにより、中央方向に流れがシフトする。段差部中央では外側から入ってくるシース液の流れの影響によりサンプル液の流れは狭められ持ち上げられる。これにより、中央上部にサンプル液の流れが収束される。   In addition, for example, when the stepped portion having a V shape in plan view is formed by a downward recess in which the bottom surface of the groove on the inflow side channel is recessed, the flow of the sheath liquid outside the channel enters the stepped portion. By hitting the part wall surface, the flow shifts in the central direction. At the center of the stepped portion, the flow of the sample liquid is narrowed and lifted by the influence of the flow of the sheath liquid entering from the outside. Thereby, the flow of the sample solution is converged at the upper center.

以下にこの発明の実施の形態について説明する。なお、それによって、この発明は限定されるものではない。
図１〜図４は、この発明の第１の実施の形態を示す。図１〜図４において、図１２〜図１７に示した符号と同一のものは、同一または相当物である。 Embodiments of the present invention will be described below. Note that the present invention is not limited thereby.
1 to 4 show a first embodiment of the present invention. 1 to 4, the same reference numerals as those shown in FIGS. 12 to 17 are the same or equivalent.

この発明が従来例と異なる点は、シース液の流れで挟み込まれたサンプル液の流れを収束させる段差部を流入側の流路に設けた点である。   The present invention is different from the conventional example in that a step portion for converging the flow of the sample liquid sandwiched between the sheath liquid flows is provided in the flow path on the inflow side.

図１〜図４において、サンプル液導入路８７ａは、平面視において一対のシース液導入路８３ａ，８３ｂ間に設けられている。そして、流入側の流路８３と流出側の流路８４との間にはインピーダンス変化検出用の絞り部８２が設けられており、絞り部８２を挟む状態で、流入側の流路８３には電極８５が、流出側の流路８４には電極８６が設けられている。この実施の形態では、電極８５は絞り部８２の直上流側に設けられ、電極８６は絞り部８２の直下流側に設けられている。また、流入側の流路８３、絞り部８２、流出側の流路８４、サンプル液導入路８７ａおよび二つのシース液導入路８３ａ，８３ｂは、シリコン基板８０上に形成された微小な幅ｂ（例えば１００μｍ），ｃ（例えば１１０μｍ）と微小な深さａ（例えば４０μｍ）を有する溝１によって形成されている。そして、流入側の流路８３、絞り部８２、流出側の流路８４、サンプル液導入路８７ａおよび二つのシース液導入路８３ａ，８３ｂは、シリコン基板８０上に接合されたガラス板Ｇによって外部と遮断された状態で閉塞されている。サンプル液導入路８７ａおよび二つのシース液導入路８３ａ，８３ｂの溝１ａ，１ｂ，１ｂの幅は、流入側の流路８３および流出側の流路８４の溝１ｃ，１ｄの幅よりも小さく設定されている。   1 to 4, the sample liquid introduction path 87a is provided between the pair of sheath liquid introduction paths 83a and 83b in a plan view. A restriction 82 for impedance change detection is provided between the inflow-side flow path 83 and the outflow-side flow path 84, and the inflow-side flow path 83 is sandwiched between the inflow-side flow paths 83. An electrode 86 is provided in the flow path 84 on the outflow side. In this embodiment, the electrode 85 is provided immediately upstream of the throttle portion 82, and the electrode 86 is provided immediately downstream of the throttle portion 82. In addition, the inflow side flow path 83, the throttle portion 82, the outflow side flow path 84, the sample liquid introduction path 87 a and the two sheath liquid introduction paths 83 a and 83 b have a small width b ( For example, the groove 1 is formed by a groove 1 having 100 μm) and c (for example 110 μm) and a minute depth a (for example 40 μm). The inflow side flow path 83, the throttle portion 82, the outflow side flow path 84, the sample liquid introduction path 87 a, and the two sheath liquid introduction paths 83 a and 83 b are externally provided by a glass plate G joined on the silicon substrate 80. It is blocked in a blocked state. The widths of the grooves 1a, 1b, 1b of the sample liquid introduction path 87a and the two sheath liquid introduction paths 83a, 83b are set smaller than the widths of the grooves 1c, 1d of the inflow side flow path 83 and the outflow side flow path 84. Has been.

以下この発明の特徴的構成について説明する。
２は段差部で、この実施の形態では、サンプル液導入路８７ａおよびシース液導入路８３ａ，８３ｂが合流する流入側の流路８３における下面側に設けられている。すなわち、この実施の形態では、段差部２は流入側の流路８３の入口部分に設けられている。具体的には、前記段差部２は、この実施の形態では平面視Ｖ型形状をなしており、この平面視Ｖ型形状の段差部２は、流入側の流路８３の溝１ｃの底面３から凸状に突出してなる上向き突起によって形成されている。この突出長さＩは溝１の深さａの１０〜９０％、好ましくは溝１の深さａの５０％の長さに設定するのがよく、この実施の形態では溝１の深さａの半分の長さ（２０μｍ）に設定されている。そして、平面視Ｖ型形状の段差部２は、この両端４，５が流入側の流路８３の合流位置９４の溝側壁６に連設されており、両端４，５から流入側の流路８３における下流側の流れ中央に向かって突出する先端７を有している。
なお、この実施の形態では前記段差部２の縦断面形状を図４に示すように矩形形状に形成しているがこの形状に限られるものではなく、台形形状、なだらかに湾曲した頂上部分を有する山形形状、鋭角的に尖った頂上部分を有する山形形状、対向する脚部分が互いに内側になだらかに湾曲している台形形状などの縦断面形状の段差部も適用できる。 The characteristic configuration of the present invention will be described below.
In this embodiment, reference numeral 2 denotes a stepped portion, which is provided on the lower surface side of the inflow side flow path 83 where the sample liquid introduction path 87a and the sheath liquid introduction paths 83a and 83b merge. That is, in this embodiment, the stepped portion 2 is provided at the inlet portion of the flow path 83 on the inflow side. Specifically, the stepped portion 2 has a V shape in plan view in this embodiment, and the stepped portion 2 in the plan view V shape has a bottom surface 3 of the groove 1c of the flow channel 83 on the inflow side. Are formed by upward projections protruding in a convex shape. The protruding length I is set to 10 to 90% of the depth a of the groove 1, preferably 50% of the depth a of the groove 1, and in this embodiment, the depth a of the groove 1 is set. Is set to a half length (20 μm). In the V-shaped step portion 2 in plan view, both ends 4 and 5 are connected to the groove side wall 6 at the joining position 94 of the inflow side flow path 83, and the inflow side flow path from both ends 4 and 5. 83 has a tip 7 projecting toward the flow center on the downstream side.
In this embodiment, the vertical cross-sectional shape of the stepped portion 2 is formed in a rectangular shape as shown in FIG. A stepped portion having a vertical cross section such as a chevron shape, a chevron shape having a sharply sharp apex portion, or a trapezoidal shape in which opposing leg portions are gently curved inward from each other can also be applied.

而して、段差部２により、サンプル液の流れＳは上部に押し上げられる（図３）とともに、両サイドのシース液８８，８９は段差部２の上流側壁面８によって段差部２の中央の先端７の方向に流れＦ1 ，Ｆ2 が変更される。さらにサンプル液の流れＳを押し上げる作用が生じ、段差部２を通過したサンプル液８７は、流路断面形状が図２（Ｂ）で示す合流位置９４での高さ（深さ）のままではなく、シース液の流れＦ1 ，Ｆ2 がサンプル液の流れＳの下部にもぐり込み、サンプル液の流れＳの下方でシース液の流れＦ1 ，Ｆ2 が合体し、図２（Ｃ）で示すように高さ（深さ）がＤ方向に大きく絞られてａ’と小さくなった状態となるとともに、シース液の流れＦ1 ，Ｆ2 は段差部２を超えることで、サンプル液の流れＳよりも流速が速まり、この流速の差によりシース液の流れＦ1 ，Ｆ2 によってサンプル液の流れＳはＷ方向に絞られてｅ’と小さくなった状態となる。このように段差部２を通過したサンプル液の流れＳの高さ（深さ）が大きく収束するとともにサンプル液の流れＳの幅も収束し、この状態でサンプル液８７は流入側の流路８４を流れることになる。流入側の流路８４を通過したサンプル液８７は絞り部８２を流れるときに前記幅ｅ’が絞り部８２の幅に見合った幅ｅ’’に絞られて小さくなる。すなわち、段差部２が底面３から凸状に突出してなる上向き突起に形成されたこの実施形態では、絞り部８２において、サンプル液の流れＳは流路８１の中央上部に収束される。そのため、サンプル液８７が絞り部８２を流れるとき、得られる検出信号、例えば電極と電極間のインピーダンスの変化を示す検出信号や、例えばレーザ光散乱によって得られる検出信号のＳ／Ｎ比を向上させることができる。 Thus, the flow S of the sample liquid is pushed upward by the step portion 2 (FIG. 3), and the sheath liquids 88 and 89 on both sides are moved to the tip of the center of the step portion 2 by the upstream side wall surface 8 of the step portion 2. The flows F 1 and F 2 are changed in the direction 7. Furthermore, the action of pushing up the flow S of the sample liquid occurs, and the sample liquid 87 that has passed through the stepped portion 2 does not have the flow path cross-sectional shape at the height (depth) at the joining position 94 shown in FIG. 2, the sheath liquid flows F 1 and F 2 dig into the lower part of the sample liquid flow S, and the sheath liquid flows F 1 and F 2 are combined below the sample liquid flow S, as shown in FIG. In this way, the height (depth) is greatly reduced in the D direction and becomes a 'small, and the sheath liquid flows F 1 and F 2 exceed the step portion 2, thereby causing the sample liquid flow S. As a result, the flow rate of the sample liquid S is reduced in the W direction by the sheath liquid flows F 1 and F 2 , and is reduced to e ′. In this way, the height (depth) of the sample liquid flow S that has passed through the stepped portion 2 is largely converged and the width of the sample liquid flow S is also converged. In this state, the sample liquid 87 flows into the inflow channel 84. Will flow. When the sample liquid 87 that has passed through the inflow channel 84 flows through the throttle 82, the width e ′ is reduced to a width e ″ that matches the width of the throttle 82, and becomes smaller. That is, in this embodiment in which the stepped portion 2 is formed as an upward projection protruding in a convex shape from the bottom surface 3, the sample liquid flow S is converged on the center upper portion of the flow path 81 in the throttle portion 82. Therefore, when the sample liquid 87 flows through the restricting portion 82, the S / N ratio of the detection signal obtained, for example, a detection signal indicating a change in impedance between the electrodes or a detection signal obtained by, for example, laser light scattering is improved. be able to.

図５は、平面視Ｖ型形状の段差部２を、流入側の流路８３の溝１ｃの底面３を凹ませてなる下向き凹所によって形成したこの発明の第２の実施の形態を示す。この実施の形態でも、段差部２は流入側の流路８３の入口部分に設けられている。図５において、図１〜図４に示した符号と同一のものは同一または相当物である。   FIG. 5 shows a second embodiment of the present invention in which the stepped portion 2 having a V shape in plan view is formed by a downward recess formed by recessing the bottom surface 3 of the groove 1c of the flow channel 83 on the inflow side. Also in this embodiment, the stepped portion 2 is provided at the inlet portion of the flow path 83 on the inflow side. 5, the same reference numerals as those shown in FIGS. 1 to 4 are the same or equivalent.

この実施の形態では、段差部２の壁面によってシース液の流れＦ1 ，Ｆ2 が段差部２の中央の先端７の方向に変更され、これによってサンプル液の流れＳの幅方向が収束される。また、段差部２によってシース液の流れＦ1 ，Ｆ2 がサンプル液の流れＳの下にもぐることになり、サンプル液の流れＳがシース液の流れＦ1 ，Ｆ2 によって押し上げられる。これによってサンプル液の流れＳの高さ方向が収束される。そして、絞り部８２において、サンプル液の流れＳは流路８１の中央上部に収束される。なお、段差部２の凹み長さＴは例えば溝１の深さａの１０〜９０％、好ましくは溝１の深さａの５０％の長さに設定するのがよく、この実施の形態では溝１の深さａの半分の長さ（２０μｍ）に設定されている。なお、この実施の形態では前記段差部２の縦断面形状を図５に示すように矩形形状に形成しているがこの形状に限られるものではなく、逆台形形状など適宜の縦断面形状に形成された段差部も適用できる。 In this embodiment, the flow of sheath liquid F 1 , F 2 is changed by the wall surface of the stepped portion 2 in the direction of the center tip 7 of the stepped portion 2, thereby converging the width direction of the sample liquid flow S. . Further, the step liquid 2 causes the sheath liquid flows F 1 and F 2 to go under the sample liquid flow S, and the sample liquid flow S is pushed up by the sheath liquid flows F 1 and F 2 . Thereby, the height direction of the flow S of the sample liquid is converged. Then, the flow S of the sample liquid is converged on the upper center of the flow path 81 in the throttle portion 82. The recess length T of the stepped portion 2 is set to, for example, 10 to 90% of the depth a of the groove 1, and preferably 50% of the depth a of the groove 1, and in this embodiment, The length is set to half the depth a of the groove 1 (20 μm). In this embodiment, the vertical cross-sectional shape of the stepped portion 2 is formed in a rectangular shape as shown in FIG. 5, but is not limited to this shape, and is formed in an appropriate vertical cross-sectional shape such as an inverted trapezoidal shape. The stepped portion can also be applied.

図６は、平面視Ｖ型形状の段差部２を、ガラス板Ｇの底面１０から下方側に凸状に突出してなる下向き突起によって形成したこの発明の第３の実施の形態を示す。この実施の形態でも、段差部２は流入側の流路８３の入口部分に設けられている。図６において、図１〜図５に示した符号と同一のものは同一または相当物である。   FIG. 6 shows a third embodiment of the present invention in which the stepped portion 2 having a V shape in plan view is formed by a downward projection that protrudes downward from the bottom surface 10 of the glass plate G. As shown in FIG. Also in this embodiment, the stepped portion 2 is provided at the inlet portion of the flow path 83 on the inflow side. 6, the same reference numerals as those shown in FIGS. 1 to 5 are the same or equivalent.

この実施の形態では、作用は上記第１の実施の形態の場合と同じであり、上記第１の実施の形態の場合と異なる点は、絞り部８２において、サンプル液の流れＳは流路８１の中央下部に収束される点である。   In this embodiment, the operation is the same as in the case of the first embodiment, and the point different from the case of the first embodiment is that the flow S of the sample liquid in the throttle portion 82 is the flow path 81. It is a point that converges to the lower center of.

なお、平面視Ｖ型形状の段差部２を、ガラス板Ｇの底面１０を上方側に凹ませてなる上向き凹所によって形成してもよい。この場合の作用は上記第２の実施の形態の場合と同じであり、上記第２の実施の形態の場合と異なる点は、絞り部８２において、サンプル液の流れＳは流路８１の中央下部に収束される点である。   Note that the stepped portion 2 having a V-shape in plan view may be formed by an upward recess formed by denting the bottom surface 10 of the glass plate G upward. The operation in this case is the same as that in the second embodiment, and the difference from the case of the second embodiment is that the sample liquid flow S is lower in the center of the flow path 81 in the throttle 82. It is a point that converges.

また、上記各実施の形態では、平面視Ｖ型形状の段差部２を、流入側の流路８３の溝１ｃの底面３やガラス板Ｇの底面１０に一つずつ設けたものを示したが、平面視Ｖ型形状の段差部２を底面３，１０の両方に設けた場合にもこの発明は適用できる。   In each of the above embodiments, the stepped portion 2 having a V-shape in plan view is provided on the bottom surface 3 of the groove 1c of the flow channel 83 on the inflow side and the bottom surface 10 of the glass plate G one by one. The present invention can also be applied to the case where the stepped portions 2 having a V shape in plan view are provided on both the bottom surfaces 3 and 10.

ここまでの各実施の形態では、平面視Ｖ型形状の段差部２をサンプル液導入路８７ａおよびシース液導入路８３ａ，８３ｂが合流する流入側の流路８３における上面側および／または下面側に設けたものを示したが、平面視Ｖ型形状に限らず、段差部２を、図７，８に示すような平面視山型形状に形成してもよく、また、段差部２を、図９および１０に示すようなそれぞれ平面視Ｕ型形状および平面視Ｗ型形状に形成してもよい。   In each of the embodiments so far, the stepped portion 2 having a V shape in plan view is formed on the upper surface side and / or the lower surface side in the inflow side flow channel 83 where the sample liquid introduction channel 87a and the sheath liquid introduction channels 83a and 83b merge. Although provided, the stepped portion 2 is not limited to the V shape in plan view, and the stepped portion 2 may be formed in a mountain shape in plan view as shown in FIGS. You may form in a planar view U shape and planar view W shape as shown to 9 and 10, respectively.

図７に示す平面視山型形状の段差部２は、両端１２，１３から流入側の流路８３における下流側の流れ中央に向かって両辺ｍ，ｎが流れ中央側に湾曲しながら突出してなるものである。この実施の形態でも、段差部２は流入側の流路８３の入口部分に設けられている。   The step portion 2 having a mountain shape in a plan view shown in FIG. 7 is formed by projecting both sides m and n from both ends 12 and 13 toward the flow center on the downstream side in the flow channel 83 on the inflow side while curving toward the flow center side. Is. Also in this embodiment, the stepped portion 2 is provided at the inlet portion of the flow path 83 on the inflow side.

また、図８に示す平面視山型形状の段差部２は、両端１２，１３から流入側の流路８３における下流側の流れ中央に向かって両辺ｍ，ｎが流れ中央側から外側に湾曲しながら突出してなるものである。この実施の形態でも、段差部２は流入側の流路８３の入口部分に設けられている。   Further, in the stepped portion 2 having a mountain shape in a plan view shown in FIG. 8, both sides m and n are curved outward from the flow center side toward both ends 12 and 13 toward the flow center on the downstream side in the flow channel 83 on the inflow side. However, it protrudes. Also in this embodiment, the stepped portion 2 is provided at the inlet portion of the flow path 83 on the inflow side.

上記各実施の形態では、段差部２を流入側の流路８３の入口部分に設けたものを示したが、これに限られるものではない。例えば、図１１は、平面視Ｖ型形状の段差部２を流入側の流路８３の途中に設けたこの発明の実施の形態を示す。図１１において、図１〜図１０に示した符号と同一のものは同一または相当物である。   In each of the above-described embodiments, the stepped portion 2 is provided at the inlet portion of the inflow side flow path 83, but the present invention is not limited to this. For example, FIG. 11 shows an embodiment of the present invention in which a stepped portion 2 having a V shape in plan view is provided in the middle of the flow path 83 on the inflow side. 11, the same reference numerals as those shown in FIGS. 1 to 10 are the same or equivalent.

図１１において、平面視Ｖ型形状の段差部２は、この両端４，５が流入側の流路８３の溝側壁６における中間部に連設されており、両端４，５から流入側の流路８３における下流側の流れ中央に向かって突出する先端７を有している。すなわち、この実施の形態では、段差部２の両端４，５が合流位置９４から流入側の流路８３における下流側に所定距離Ｋだけ離れて位置している。   In FIG. 11, the stepped portion 2 having a V shape in plan view has both ends 4, 5 connected to an intermediate portion in the groove side wall 6 of the flow path 83 on the inflow side. The passage 83 has a tip 7 that protrudes toward the center of the downstream flow. That is, in this embodiment, both ends 4 and 5 of the stepped portion 2 are located at a predetermined distance K away from the joining position 94 on the downstream side in the inflow side flow path 83.

また、この発明では、図１１に仮想線で示すように、流入側の流路８３の途中に流路幅が部分的に絞られた絞り部分２００を設けてもよい。   In the present invention, as shown by the phantom line in FIG. 11, a throttle portion 200 having a partially narrowed channel width may be provided in the middle of the channel 83 on the inflow side.

なお、上記各実施の形態では、サンプル液の流れをシース液の流れによって挟み込むように二つのシース液導入路間にサンプル液導入路を設けるタイプのマイクロチップを示したが、一つのシース液導入路とサンプル液導入路を設けるタイプのマイクロチップにもこの発明は適用できる。   In each of the above embodiments, the microchip of the type in which the sample liquid introduction path is provided between the two sheath liquid introduction paths so that the flow of the sample liquid is sandwiched by the flow of the sheath liquid is shown. The present invention can also be applied to a microchip having a channel and a sample solution introduction channel.

この発明の第１の実施の形態を示す平面図である。It is a top view which shows 1st Embodiment of this invention. （Ａ）は、上記実施の形態における流路を示す平面図である。（Ｂ）は、図２（Ａ）におけるＸ−Ｘ´線断面図を示す。（Ｃ）は、図２（Ａ）におけるＹ−Ｙ´線断面図を示す。（Ｄ）は、図２（Ａ）におけるＺ−Ｚ´線断面図を示す。(A) is a top view which shows the flow path in the said embodiment. FIG. 2B is a sectional view taken along line XX ′ in FIG. FIG. 2C is a cross-sectional view taken along line YY ′ in FIG. FIG. 2D is a cross-sectional view taken along the line ZZ ′ in FIG. 上記実施の形態における流路を示す斜視図である。It is a perspective view which shows the flow path in the said embodiment. 上記実施の形態における流路を示す縦断面図である。It is a longitudinal cross-sectional view which shows the flow path in the said embodiment. この発明の第２の実施の形態における流路を示す縦断面図である。It is a longitudinal cross-sectional view which shows the flow path in 2nd Embodiment of this invention. この発明の第３の実施の形態における流路を示す縦断面図である。It is a longitudinal cross-sectional view which shows the flow path in 3rd Embodiment of this invention. この発明で用いる段差部の第１の変形例を含む流路を示す平面図である。It is a top view which shows the flow path containing the 1st modification of the level | step-difference part used by this invention. この発明で用いる段差部の第２の変形例を含む流路を示す平面図である。It is a top view which shows the flow path containing the 2nd modification of the level | step-difference part used by this invention. この発明で用いる段差部の第３の変形例を含む流路を示す平面図である。It is a top view which shows the flow path containing the 3rd modification of the level | step-difference part used by this invention. この発明で用いる段差部の第４の変形例を含む流路を示す平面図である。It is a top view which shows the flow path containing the 4th modification of the level | step-difference part used by this invention. この発明の更に他の変形例を示す平面図である。It is a top view which shows the further another modification of this invention. 従来例を示す平面図である。It is a top view which shows a prior art example. （Ａ）は、従来例における流路を示す平面図である。（Ｂ）は、図１３（Ａ）におけるＸ−Ｘ´線断面図を示す。（Ｃ）は、図１３（Ａ）におけるＹ−Ｙ´線断面図を示す。（Ｄ）は、図１３（Ａ）におけるＺ−Ｚ´線断面図を示す。(A) is a top view which shows the flow path in a prior art example. FIG. 13B is a sectional view taken along line XX ′ in FIG. FIG. 13C is a sectional view taken along line YY ′ in FIG. FIG. 13D is a sectional view taken along line ZZ ′ in FIG. 比較例を示す正面図である。It is a front view which shows a comparative example. （Ａ）は、別の比較例における流路を示す平面図である。（Ｂ）は、図１５（Ａ）におけるＨ−Ｈ´線断面図を示す。(A) is a top view which shows the flow path in another comparative example. FIG. 15B is a sectional view taken along line HH ′ in FIG. 更に別の比較例における流路を示す平面図である。It is a top view which shows the flow path in another comparative example. 別の比較例における流路を示す平面図である。It is a top view which shows the flow path in another comparative example.

符号の説明Explanation of symbols

２ 段差部
８２ 絞り部
８３ 流入側の流路 ８３ａ，８３ｂ シース液導入路
８４ 流出側の流路
８７ａ サンプル液導入路
８７ サンプル液
８８，８９ シース液
Ｓ サンプル液の流れ
Ｆ1 ，Ｆ2 シース液の流れ
2 Step part 82 Stop part
83 Inflow side flow path 83a, 83b Sheath liquid introduction path 84 Outflow side flow path 87a Sample liquid introduction path 87 Sample liquid 88, 89 Sheath liquid S Sample liquid flow F 1 , F 2 sheath liquid flow

Claims (9)

流入側の流路と、流出側の流路と、流入側の流路の上流側に合流するよう設けたサンプル液導入路およびシース液導入路とを備え、サンプル液の流れをシース液の流れによって挟み込むようにしてあるマイクロチップにおいて、シース液の流れで挟み込まれたサンプル液の流れを収束させる段差部を流入側の流路に設けてあることを特徴とするマイクロチップ。   A flow path on the inflow side, a flow path on the outflow side, and a sample liquid introduction path and a sheath liquid introduction path provided so as to merge upstream of the flow path on the inflow side. A microchip characterized in that a step portion for converging the flow of the sample liquid sandwiched by the flow of the sheath liquid is provided in the flow path on the inflow side. 段差部を、前記流入側の流路の上面側および／または下面側に設けてある請求項１に記載のマイクロチップ。   The microchip according to claim 1, wherein a step portion is provided on an upper surface side and / or a lower surface side of the flow path on the inflow side. サンプル液導入路は、平面視において一対のシース液導入路間に設けられており、また、流入側の流路、流出側の流路、サンプル液導入路およびシース液導入路は、基板上に形成された微小な幅を有する溝によって形成されるとともに、これらは閉塞部によって外部と遮断された状態で閉塞されており、サンプル液導入路およびシース液導入路の溝の幅は、流入側の流路および流出側の流路の溝の幅よりも小さく設定される一方、段差部は、平面視Ｖ型形状で、両端が流入側の流路の溝側壁に連設され、下流側の流れ中央に向かって突出する先端を有する請求項１または請求項２に記載のマイクロチップ。   The sample liquid introduction path is provided between the pair of sheath liquid introduction paths in plan view, and the inflow side flow path, the outflow side flow path, the sample liquid introduction path, and the sheath liquid introduction path are formed on the substrate. These are formed by grooves having a very small width, and these are blocked from the outside by a blocking portion, and the widths of the grooves in the sample liquid introduction path and the sheath liquid introduction path are on the inflow side. The step portion is set to be smaller than the width of the groove of the flow channel and the flow channel on the outflow side, while the stepped portion has a V shape in plan view, and both ends are connected to the groove side wall of the flow channel on the inflow side. The microchip according to claim 1, wherein the microchip has a tip protruding toward the center. 平面視Ｖ型形状の段差部は、流入側の流路の溝の底面から凸状に突出してなる上向き突起によって形成されるか、または、流入側の流路の溝の底面を凹ませてなる下向き凹所によって形成されるか、または、閉塞部の底面から下方側に凸状に突出してなる下向き突起によって形成されるか、または、閉塞部の底面を上方側に凹ませてなる上向き凹所によって形成されるかのいずれか、またはこれらの組み合わせによって形成される請求項３に記載のマイクロチップ。   The step portion having a V shape in plan view is formed by an upward projection protruding in a convex shape from the bottom surface of the groove on the inflow side channel, or the bottom surface of the groove on the inflow side channel is recessed. An upward recess formed by a downward recess, or formed by a downward projection that protrudes downward from the bottom surface of the blocking portion, or by denting the bottom surface of the blocking portion upward. 4. The microchip according to claim 3, wherein the microchip is formed by any one of or a combination thereof. 段差部は、平面視Ｕ型形状、平面視Ｗ型形状、両端から流入側の流路における下流側の流れ中央に向かって両辺が流れ中央側に湾曲しながら突出してなる平面視山型形状、両端から流入側の流路における下流側の流れ中央に向かって両辺が流れ中央側から外側に湾曲しながら突出してなる平面視山型形状を有する請求項１または請求項２に記載のマイクロチップ。   The stepped portion has a U-shape in a plan view, a W-shape in a plan view, and a mountain-like shape in a plan view in which both sides protrude from the both ends toward the flow center on the downstream side in the flow path on the inflow side while curving toward the flow center side. 3. The microchip according to claim 1, wherein the microchip has a mountain shape in a plan view in which both sides protrude from the both ends toward the downstream flow center in the flow path on the inflow side while curving outward from the flow center side. 前記平面視Ｕ型形状、前記平面視Ｗ型形状および前記二種類の平面視山型形状の段差部は、それぞれ、流入側の流路の溝の底面から凸状に突出してなる上向き突起によって形成されるか、または、流入側の流路の溝の底面を凹ませてなる下向き凹所によって形成されるか、または、閉塞部の底面から下方側に凸状に突出してなる下向き突起によって形成されるか、または、閉塞部の底面を上方側に凹ませてなる上向き凹所によって形成されるかのいずれか、またはこれらの組み合わせによって形成される請求項５に記載のマイクロチップ。   The step portions of the U shape in plan view, the W shape in plan view, and the two types of mountain shape in plan view are each formed by an upward projection that protrudes in a convex shape from the bottom surface of the groove of the channel on the inflow side. Or formed by a downward recess formed by denting the bottom surface of the groove of the flow channel on the inflow side, or formed by a downward projection protruding convexly downward from the bottom surface of the blocking portion. 6. The microchip according to claim 5, wherein the microchip is formed by an upward recess formed by recessing the bottom surface of the closing portion upward, or a combination thereof. 流入側の流路と流出側の流路との間に絞り部を設けてある請求項１〜請求項６のいずれかに記載のマイクロチップ。   The microchip according to any one of claims 1 to 6, wherein a throttle portion is provided between the flow path on the inflow side and the flow path on the outflow side. サンプル液導入路およびシース液導入路をこれらの下流に設けた流入側の流路に合流させてサンプル液の流れをシース液の流れによって挟み込み、さらに、シース液の流れで挟み込まれたサンプル液の流れを、流入側の流路に設けた段差部によって収束させるようにしたことを特徴とするマイクロチップ中における流体制御方法。   The sample liquid introduction path and the sheath liquid introduction path are joined to the inflow side flow path provided downstream of these, and the flow of the sample liquid is sandwiched by the flow of the sheath liquid, and further, the sample liquid sandwiched by the flow of the sheath liquid A fluid control method in a microchip, wherein the flow is converged by a step portion provided in a flow path on an inflow side. シース液の流れで挟み込まれたサンプル液の流れを段差部によって収束させた後、これが通過する絞り部を流入側の流路と流出側の流路との間に設けている請求項８に記載のマイクロチップ中における流体制御方法。
The flow of the sample liquid sandwiched by the flow of the sheath liquid is converged by the step portion, and then a throttle portion through which the flow passes is provided between the inflow side flow path and the outflow side flow path. Of fluid control in a microchip.
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