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JP2007175684A - Flow passage structure and method for concentration and classification of fine particle - Google Patents

Flow passage structure and method for concentration and classification of fine particle Download PDF

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JP2007175684A
JP2007175684A JP2005381256A JP2005381256A JP2007175684A JP 2007175684 A JP2007175684 A JP 2007175684A JP 2005381256 A JP2005381256 A JP 2005381256A JP 2005381256 A JP2005381256 A JP 2005381256A JP 2007175684 A JP2007175684 A JP 2007175684A
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fluid
flow path
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Minoru Seki
実 関
Masumi Yamada
真澄 山田
Miyuki Matsuda
美由紀 松田
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Advance Co Ltd
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • 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
    • B01L3/502753Containers 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 bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
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    • B01L2200/06Fluid handling related problems
    • B01L2200/0647Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0652Sorting or classification of particles or molecules

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Abstract

<P>PROBLEM TO BE SOLVED: To provide a fine particle concentrating and classifying mechanism and its apparatus recovering large particles without containing small particles. <P>SOLUTION: Flow passage structure is used having at least one branch point 17 on the side face of the flow passage 11, and at least one branch passage 12 connected to the flow passage at the branch point and having at least one of scales such as length, width, depth or diameter properly adjusted. Fluid is introduced to the flow passage to be separated into fluid containing particles and fluid containing no particles, and at the branch point, particles of a certain size or larger are made not to enter the branch passage, and particles of a certain size or smaller are made not to enter the downstream side of the branch passage. Thus, the fluid containing all of the introduced particles of a certain size or smaller, or the fluid containing no particles of a certain size or larger, is recovered from the branch passage, to recover the fluid with increased concentration of particles of a certain size or larger from the downstream side of the passage. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

発明の詳細な説明Detailed Description of the Invention

本発明は、微粒子の濃縮・分級方法に関し、さらに詳細には、動植物細胞、オルガネラ、微生物、エアロゾル、セラミック粒子、ポリマー粒子、エマルション、無機粒子、金属ナノ粒子などの粒子を濃縮し、分級する際に用いて好適な微粒子の濃縮・分級方法に関する。  The present invention relates to a method for concentrating and classifying fine particles, and more specifically, when concentrating and classifying particles such as animal and plant cells, organelles, microorganisms, aerosols, ceramic particles, polymer particles, emulsions, inorganic particles, and metal nanoparticles. The present invention relates to a method for concentrating and classifying fine particles suitable for use in the above.

一般に、動植物細胞、オルガネラ、微生物などの粒子を濃縮・分級する方法は、基礎研究のみならず、血液からの造血幹細胞の分離・濃縮といった医学分野や、環境中に存在する菌の分離などの分野において重要である。  In general, methods for concentrating and classifying particles such as animal and plant cells, organelles, and microorganisms are not only used for basic research, but also for medical fields such as the separation and concentration of hematopoietic stem cells from blood, and for the isolation of bacteria present in the environment. Is important.

また、エアロゾル、セラミック粒子、ポリマー粒子、エマルション、無機粒子、金属ナノ粒子などの粒子を濃縮・分級する方法は、化学工学、粉体工業、電子産業、精密機械工業などの分野において重要である。  In addition, methods for concentrating and classifying particles such as aerosols, ceramic particles, polymer particles, emulsions, inorganic particles, and metal nanoparticles are important in fields such as chemical engineering, powder industry, electronics industry, and precision machinery industry.

従来の微粒子を分級する技術としては、例えばフローサイトメトリーを利用した分離方法があり、他にも一般的に、遠心分離法、沈降分離法、静電気を用いた分離方法、フィルトレーション、フィールドフローフラクショネーションなどが知られている。  As a conventional technology for classifying fine particles, for example, there is a separation method using flow cytometry. In addition, generally, a centrifugal separation method, a sedimentation separation method, a separation method using static electricity, filtration, field flow, and the like. Fractionation is known.

しかし、フローサイトメトリーでは対象となる粒子を蛍光でラベルする必要があり、また、大量処理が困難であり、複雑な装置が必要となるといった問題点があった。  However, in flow cytometry, it is necessary to label the target particles with fluorescence, and it is difficult to perform a large amount of processing, which requires a complicated apparatus.

また、遠心分離法、沈降分離法、静電気を用いた分離方法では、一度に大量の粒子を処理することが可能である反面、分級精度が低い、粒径が極めて小さいものを分離することが困難である、などといった問題点があった。  In addition, the centrifugal separation method, the sedimentation separation method, and the separation method using static electricity can process a large amount of particles at one time, but on the other hand, it is difficult to separate those with low classification accuracy and extremely small particle size. There was a problem such as.

また、フィルトレーション、フィールドフローフラクショネーションでは、分級精度は高いが、分離する際に時間が多くかかってしまう、一度に大量処理ができない、連続的な操作ができない、といった問題点があった。  In addition, filtration and field flow fractionation have high classification accuracy, but it takes a lot of time to separate, and there are problems such as being unable to process a large amount at a time and continuous operation. .

また近年、微細加工技術を用いて作製した流路構造を持つ、マイクロ流路デバイスでの微粒子の分級・濃縮方法が提案されており、この方法では重力、遠心力、電場、磁場などの外部からの力を用いることなく、粒子を含んだ流体をある特定の流路構造に導入するだけで、粒子を大きさによって分離することが可能である。
特願2005−232590
In recent years, a method for classifying and concentrating fine particles in a micro-channel device with a channel structure fabricated using microfabrication technology has been proposed. In this method, external force such as gravity, centrifugal force, electric field, and magnetic field is proposed. It is possible to separate particles according to size by simply introducing a fluid containing particles into a specific flow channel structure without using a force of.
Japanese Patent Application No. 2005-232590

しかしながら、これらの方法では粒子を含む流体のみを導入するということで、導入した全ての粒子を回収することができず、また、小さな粒子のみを回収することは可能であるが、大きな粒子を回収する際には小さな粒子が含まれてしまうという問題点がある。  However, in these methods, only the fluid containing particles is introduced, so that all the introduced particles cannot be recovered, and only small particles can be recovered, but large particles are recovered. When doing so, there is a problem that small particles are included.

発明が解決する課題Problems to be solved by the invention

本発明は、従来の技術の有する上記のような問題点を鑑みてなされたものであり、その目的とするところは、動植物細胞、オルガネラ、微生物、エアロゾル、セラミック粒子、ポリマー粒子、エマルション、無機粒子、金属ナノ粒子などを分離する際、粒子を認識することなく、迅速かつ大量に分離することができ、導入した全ての粒子を回収することができ、大きな粒子を回収する際にも小さな粒子が含まれることなく回収することができる、微粒子の濃縮・分級機構およびその装置を提供するものである。  The present invention has been made in view of the above-described problems of the prior art, and the object thereof is animal and plant cells, organelles, microorganisms, aerosols, ceramic particles, polymer particles, emulsions, and inorganic particles. When separating metal nanoparticles, etc., it can be separated quickly and in large quantities without recognizing the particles, all the introduced particles can be collected, and even when collecting large particles, there are small particles It is an object of the present invention to provide a fine particle concentration / classification mechanism and apparatus that can be recovered without being contained.

課題を解決するための手段Means for solving the problem

上記目的を達成するため、本発明は、途中に少なくとも1つの分岐流路を持つ流路に、粒子を含む流体と粒子を含まない流体を連続的に導入した際、流路の下流または分岐流路の下流へと導入される流量は、それぞれの流路の幅、長さ、深さ、径などにより決定され、さらに粒子の挙動は流路の大きさと流体の分配比によって支配されるということに着目してなされたものである。  In order to achieve the above object, the present invention provides a downstream or branched flow of a channel when a fluid containing particles and a fluid not containing particles are continuously introduced into a channel having at least one branch channel on the way. The flow rate introduced downstream of the channel is determined by the width, length, depth, diameter, etc. of each channel, and the particle behavior is governed by the channel size and fluid distribution ratio. It was made paying attention to.

本発明のうち請求項1に記載の発明は、所定の方向に延長される流路Aと、流路Aの側面における1つ以上の分岐点と、前記分岐点において前記流路Aに接続され、長さ、幅、深さ、径などのスケールのうちいずれか1つ以上が適当に調節された分岐流路を1つ以上有する流路構造を用い、前記流路Aの一端から、流体を連続的に導入する際、粒子を含む流体の部分と粒子を含まない流体の部分に分かれるように導入することにより、前記分岐点において、ある一定の大きさ以上の粒子は前記分岐点において前記分岐流路に導入されないようにすることができ、ある一定の大きさ以下の粒子は前記流路Aの下流へと導入されないようにすることができるため、導入した全てのある一定の大きさ以下の粒子を含む流体、もしくはある一定の大きさ以上の粒子を全く含まない流体を前記分岐流路から回収することができ、ある大きさ以上の粒子の濃度が高くなった流体を前記流路Aの下流から回収することができる、というものである。  The invention according to claim 1 of the present invention is connected to the flow path A, the flow path A extending in a predetermined direction, one or more branch points on the side surface of the flow path A, and the branch points. Using a flow channel structure having one or more branch flow channels in which any one or more of scales such as length, width, depth, and diameter are appropriately adjusted, fluid is supplied from one end of the flow channel A. When the particles are continuously introduced, by introducing the fluid so as to be divided into a fluid portion containing particles and a fluid portion not containing particles, particles having a certain size or more at the branch point may be separated at the branch point. It is possible to prevent the particles having a certain size or less from being introduced into the flow path, and it is possible to prevent the particles having a certain size or less from being introduced downstream of the flow path A. Fluid containing particles or a certain size The fluid containing no particles at all can be collected from the branch flow channel, and the fluid having a high concentration of particles of a certain size or more can be collected from the downstream of the flow channel A. is there.

従って、本発明のうち請求項1に記載の発明によれば、粒子を含む流体と含まない流体を流路構造内に連続的に導入させることにより、ある一定以上の大きさの粒子の濃度が、導入前の流体中の粒子濃度と比較して高くなった流体と、ある一定以上の大きさの粒子をまったく含まない流体を別々に回収することが可能となる。  Therefore, according to the first aspect of the present invention, the concentration of particles having a certain size or more can be increased by continuously introducing a fluid containing particles and a fluid not containing particles into the flow channel structure. Thus, it becomes possible to separately collect a fluid that has become higher than the particle concentration in the fluid before introduction, and a fluid that does not contain particles of a certain size or more.

さらに、分岐流路のスケールおよび本数を適当に設定することにより、導入した粒子を含む流体の中に含まれる粒子を全て分離・回収することが可能となる。  Furthermore, by appropriately setting the scale and number of branch flow paths, it is possible to separate and collect all the particles contained in the fluid containing the introduced particles.

本発明のうち請求項2に記載の発明は、所定の方向に延長される流路Aと、流路Aの側面における複数の分岐点と、前記複数の分岐点それぞれにおいて前記流路Aに接続され、長さ、幅、深さ、径がどのスケールのうちいずれか1つ以上が適当に調節された分岐流路を1つ以上有する流路構造を用い、前記流路Aの一端から、流体を連続的に導入する際、粒子を含む流体の部分と粒子を含まない流体の部分に分かれるように導入することにより、前記複数の分岐点のうちの少なくとも1つの分岐点において、ある一定の大きさ以上の粒子は前記分岐点において前記分岐流路に導入されないようにすることができ、ある一定の大きさ以下の粒子は前記流路Aの下流へと導入されないようにすることができ、また前記複数の分岐点のうちの少なくとも1つの分岐点において、ある一定の大きさ以上の粒子が前記分岐点において前記分岐流路に導入されるようにすることができるため、導入した全てのある一定の大きさ以上の粒子は前記流路Aの壁側近傍に濃縮され、さらに、前記複数の分岐流路のいくつかから濃縮された粒子を回収することができる、というものである。  The invention according to claim 2 of the present invention is connected to the flow path A at the flow path A extending in a predetermined direction, a plurality of branch points on the side surface of the flow path A, and the plurality of branch points, respectively. A flow path structure having one or more branch flow paths in which at least one of the scales of which length, width, depth, and diameter are appropriately adjusted, from one end of the flow path A to the fluid Is introduced so as to be divided into a fluid portion containing particles and a fluid portion not containing particles, so that at least one of the plurality of branch points has a certain size. More than a certain particle can be prevented from being introduced into the branch flow path at the branch point, and a particle having a certain size or less can be prevented from being introduced downstream of the flow path A. Less than the plurality of branch points In one branch point, particles having a certain size or larger can be introduced into the branch flow path at the branch point, so that all the particles having a certain size or larger are introduced. The particles concentrated in the vicinity of the wall side of the channel A and further concentrated from some of the plurality of branch channels can be recovered.

従って、本発明のうち請求項2に記載の発明によれば、ある一定の大きさより小さい粒子を分岐流路に導入する一方で、ある一定の大きさ以上の粒子を分岐流路に導入せずに流路Aの壁面近傍に濃縮することができるため、さらに、下流の分岐流路において、ある一定の大きさ以上の粒子が濃縮された流体を回収することが可能であり、また、導入前に含まれていた全ての粒子を回収する、あるいは取り除くことも可能である。  Therefore, according to the invention described in claim 2 of the present invention, particles smaller than a certain size are introduced into the branch channel, while particles larger than a certain size are not introduced into the branch channel. In addition, it is possible to collect the fluid in which particles of a certain size or more are concentrated in the downstream branch flow path, and before the introduction, it can be concentrated in the vicinity of the wall surface of the flow path A. It is also possible to collect or remove all particles contained in the.

また、本発明のうち請求項3に記載の発明は、請求項1または請求項2のいずれか1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、前記流路Aの途中に存在する前記分岐流路は、前記流路Aの片側断面のみに存在する、というものである。  The invention according to claim 3 of the present invention is the flow channel structure and method for concentration and classification of microparticles according to any one of claim 1 or claim 2, wherein the flow channel A The branch channel existing in the middle of the channel exists only in one side cross section of the channel A.

従って、本発明のうち請求項3に記載の発明によれば、流路Aの片側の側面のみに分岐点を設けることで、導入した粒子を含む流体と粒子を含まない流体のうち、導入時点で粒子を含んでいた流体の部分を効率的に取り除くことが可能となり、粒子の回収効率を容易に高めることができ、さらに操作も容易になる。  Therefore, according to the invention described in claim 3 of the present invention, by providing a branch point only on one side surface of the flow path A, the introduction time point of the fluid containing the introduced particles and the fluid not containing the particles is introduced. Thus, it is possible to efficiently remove the portion of the fluid containing the particles, the efficiency of collecting the particles can be easily increased, and the operation is facilitated.

また、本発明のうち請求項4に記載の発明は、請求項1、請求項2または請求項3のいずれか1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、前記流路Aに流体を連続的に導入する際、粒子を含む流体の部分と粒子を含まない流体の部分に分かれるように流体を導入する方法として、入り口を複数個設け、少なくとも1つの入り口から粒子を含む流体を、少なくとも1つの入り口から粒子を含まない流体を導入する、というものである。  The invention according to claim 4 of the present invention is the flow channel structure for concentration / classification of fine particles according to any one of claims 1, 2, or 3 and the method thereof. When the fluid is continuously introduced into the flow path A, as a method of introducing the fluid so as to be divided into a fluid portion containing particles and a fluid portion not containing particles, a plurality of inlets are provided, and at least one inlet is provided. The fluid containing particles is introduced from at least one inlet.

従って、本発明のうち請求項4に記載の発明によれば、流路Aの入り口を複数個作製し、それぞれ適当な入り口から粒子を含む流体、あるいは粒子を含まない流体を導入させることにより、簡便に粒子を含む流体の部分と粒子を含まない流体の部分に分けて流体を流路Aに導入することが可能である。  Therefore, according to the invention described in claim 4 of the present invention, by preparing a plurality of inlets of the flow path A and introducing a fluid containing particles or a fluid containing no particles from each appropriate inlet, It is possible to introduce the fluid into the flow path A by dividing it into a fluid portion containing particles and a fluid portion not containing particles.

また、本発明のうち請求項5に記載の発明は、請求項3に記載の微粒子の濃縮・分級のための流路構造およびその方法において、前記流路Aに流体を連続的に導入する際、粒子を含む流体の部分と粒子を含まない流体の部分に分けて流体を導入する方法として、前記流路Aに、入口と前記分岐流路との間において一度前記流路Aから分岐し、かつ前記分岐流路よりも上流において再び前記流路Aに接続される分岐流路(迂回流路とする)を1つ以上設け、粒子を含む流体を入り口から導入させることにより、ある一定の大きさ以上の粒子を含まない流体、あるいは粒子を全く含まない流体を迂回流路に導入し、前記分岐流路よりも上流で再び前記流路Aに導入する、というものである。  The invention according to claim 5 of the present invention is the flow channel structure and method for fine particle concentration and classification according to claim 3, wherein the fluid is continuously introduced into the flow channel A. As a method of introducing the fluid into a fluid part containing particles and a fluid part not containing particles, the flow path A is once branched from the flow path A between the inlet and the branch flow path, In addition, by providing one or more branch channels (detour channels) connected to the channel A again upstream from the branch channels, a fluid containing particles is introduced from the entrance, so that a certain size is obtained. A fluid containing no more particles or a fluid containing no particles is introduced into the bypass channel, and is introduced again into the channel A upstream from the branch channel.

従って、本発明のうち請求項5に記載の発明によれば、流路Aの入り口と分岐流路の間に、ある一定以上の大きさの粒子が導入されない迂回流路を設け、その迂回流路を前記分岐点よりも上流で再び流路Aに合流させることにより、粒子を含む流体の部分と粒子を含まない流体の部分に分けて流体を流路Aに導入することが可能となるため、複数の入り口を作製し、粒子を含まない溶液を別に用意して導入しなくてもよい。  Therefore, according to the invention described in claim 5 of the present invention, a bypass flow path in which particles of a certain size or more are not introduced is provided between the entrance of the flow path A and the branch flow path. By joining the path again to the flow path A upstream from the branch point, it becomes possible to introduce the fluid into the flow path A by dividing it into a fluid portion containing particles and a fluid portion not containing particles. It is not necessary to prepare a plurality of inlets and separately prepare a solution containing no particles.

また、本発明のうち請求項6に記載の発明は、請求項3に記載の微粒子の濃縮・分級のための流路構造およびその方法において、前記流路Aに流体を連続的に導入する際、粒子を含む流体の部分と粒子を含まない流体の部分に分けて流体を導入する方法として、前記流路構造に遠心力、電場あるいは磁場を加える、というものである。  The invention according to claim 6 of the present invention is the flow channel structure and method for concentration / classification of fine particles according to claim 3, wherein the fluid is continuously introduced into the flow channel A. As a method of introducing a fluid into a fluid portion containing particles and a fluid portion not containing particles, a centrifugal force, an electric field or a magnetic field is applied to the channel structure.

従って、本発明のうち請求項6に記載の発明によれば、分岐流路が流路Aの断面において片側のみに存在する流路構造の場合、流路Aに遠心力、電場や磁場などを加えることにより、粒子を含む流体の部分と粒子を含まない流体の部分に分けて流体を流路Aに導入することが可能であるため、複数の入り口を作製し、粒子を含まない溶液を別に用意して導入しなくてもよい。  Therefore, according to the invention described in claim 6 of the present invention, when the branch channel has a channel structure that exists only on one side in the cross section of the channel A, the channel A is subjected to centrifugal force, electric field, magnetic field, and the like. In addition, since it is possible to introduce the fluid into the flow path A by dividing into a fluid portion containing particles and a fluid portion not containing particles, a plurality of inlets are created, and a solution not containing particles is separated. It is not necessary to prepare and introduce it.

また、本発明のうち請求項7に記載の発明は、請求項1、請求項2、請求項3、請求項4、請求項5または請求項6のいずれか1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、前記流路の幅、深さ、径のいずれかのスケールが、少なくとも部分的に1センチメートル以下のオーダーであり、前記流路内における流体の流れは少なくとも部分的に安定した層流になる、というものである。  In addition, the invention according to claim 7 of the present invention is the concentration / concentration of fine particles according to claim 1, claim 2, claim 3, claim 4, claim 5 or claim 6. In the flow path structure and method for classification, the scale of any of the width, depth, and diameter of the flow path is at least partially on the order of 1 centimeter or less, and the flow of fluid in the flow path Is at least partially stable laminar.

従って、本発明のうち請求項7に記載の発明によれば、流路内の流れは安定した層流であるので、粒子の動きが乱れることがないため、正確な粒子の分離・濃縮が可能となる。  Therefore, according to the invention described in claim 7 of the present invention, since the flow in the flow path is a stable laminar flow, the movement of the particles is not disturbed, so that accurate separation and concentration of the particles are possible. It becomes.

また、本発明のうち請求項8に記載の発明は、請求項1、請求項2、請求項3、請求項4、請求項5、請求項6または請求項7のいずれか1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、流体とは液体である、というものである。  The invention according to claim 8 is the invention according to any one of claims 1, 2, 3, 4, 5, 6, or 7. In the flow channel structure and method for concentration / classification of fine particles, the fluid is a liquid.

従って、本発明のうち請求項8に記載の発明によれば、液体中に懸濁した粒子を分離・濃縮することが可能となる。  Therefore, according to the eighth aspect of the present invention, particles suspended in the liquid can be separated and concentrated.

また、本発明のうち請求項9に記載の発明は、請求項1、請求項2、請求項、請求項4、請求項5、請求項6または請求項7のいずれか1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、流体とは気体である、というものである。  In addition, among the present inventions, the invention according to claim 9 is the fine particle according to any one of claims 1, 2, 2, 4, 5, 6, or 7. In the flow channel structure and method for concentration / classification, the fluid is a gas.

従って、本発明のうち請求項9に記載の発明によれば、気体中に分散した粒子を分離・濃縮することが可能となる。  Therefore, according to the ninth aspect of the present invention, particles dispersed in a gas can be separated and concentrated.

また、本発明のうち請求項10に記載の発明は、請求項1、請求項2、請求項3、請求項4、請求項5、請求項6、請求項7、請求項8または請求項9のいずれかの1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、粒子とは細胞である、というものである。  Further, the invention according to claim 10 of the present invention is claimed in claim 1, claim 2, claim 3, claim 4, claim 5, claim 7, claim 8, or claim 9. In the flow channel structure and method for concentration / classification of microparticles according to any one of the above, the particles are cells.

従って、本発明のうち請求項10に記載の発明によれば、例えば、血液細胞を分離・濃縮することや、環境水中や大気中などに含まれる微生物を分離・濃縮することが可能となり、非常に有用である。  Therefore, according to the invention described in claim 10 of the present invention, for example, it becomes possible to separate and concentrate blood cells, and to separate and concentrate microorganisms contained in environmental water or the atmosphere. Useful for.

また、本発明のうち請求項11に記載の発明は、請求項1、請求項2、請求項3、請求項4、請求項5、請求項6、請求項7、請求項8、請求項9または請求項10のいずれかの1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、前記流路とはマイクロチップに形成されたマイクロチャネルである、ということである。  Further, among the present inventions, the invention described in claim 11 is the invention described in claims 1, 2, 3, 4, 5, 6, 7, 8, 9. Alternatively, in the flow channel structure and method for concentrating and classifying fine particles according to any one of claims 10, the flow channel is a microchannel formed in a microchip.

従って、本発明のうち請求項11に記載の発明によれば、流路の形状を正確にコントロールすることができ、また、流路の直列化、並列化が容易になるため、分離性能の向上や処理量の向上が期待できる。  Therefore, according to the invention described in claim 11 of the present invention, the shape of the flow path can be accurately controlled, and since the flow paths can be easily serialized and parallelized, the separation performance is improved. And improvement in throughput.

発明の効果The invention's effect

本発明は、以上に述べられたような特徴を有するため、粒子を含む流体と粒子を含まない流体を、ある形状をもつ流路に導入するだけで、導入した全ての粒子を大きさにより分離・濃縮し回収することが可能となり、更に大きな粒子を回収する際にも小さな粒子が含まれないようにすることができる、という優れた効果を発揮する。  Since the present invention has the characteristics as described above, all the introduced particles are separated by size simply by introducing a fluid containing particles and a fluid not containing particles into a channel having a certain shape. -It is possible to concentrate and collect, and when it collects larger particles, it exhibits an excellent effect that small particles are not included.

また、本発明は以上に述べられたような特徴をするため、フローサイトメトリーや遠心分離法、沈降分離法、静電気を用いた分離法などの従来の粒子の分離または濃縮技術と比較して、複雑な装置や外力を必要とせず、短時間で大きさによる粒子の分離・濃縮が可能となる、という優れた効果を発揮する。  In addition, since the present invention has the characteristics as described above, compared to conventional particle separation or concentration techniques such as flow cytometry, centrifugation, sedimentation separation, and separation using static electricity, It exhibits the excellent effect that particles can be separated and concentrated according to size in a short time without the need for complicated equipment or external force.

以下、添付の書類に基づいて、本発明による微粒子を濃縮・分離する流路構造およびその方法の形態を詳細に説明する。  Hereinafter, a flow channel structure for concentrating and separating fine particles according to the present invention and a mode of the method will be described in detail with reference to the attached documents.

図1(a)(b)には、本発明による微粒子の分離・濃縮のための流路構造およびその方法の原理が示されており、図1(a)(b)は最も基本的な粒子の分離・濃縮の一例である。  FIGS. 1 (a) and 1 (b) show the principle of the flow channel structure and method for separating and concentrating fine particles according to the present invention. FIGS. 1 (a) and 1 (b) show the most basic particles. This is an example of separation and concentration.

図1(a)において、ある所定の方向に延長される流路11は途中に分岐流路12を有しており、矢印13は流路11に導入される流体の流れの方向を表しており、矢印14,15はそれぞれ分岐流路12に導入される流体の流れの方向と、流路11の下流に導入される流体の流れの方向を示している。また、点線16は、分岐流路12に導入される流体の部分と流路11の下流に導入される流体の部分の境界を表している。なお、請求項における流路Aとは流路11のことであり、流路Aにおける分岐点は、分岐点17である。  In FIG. 1A, a flow path 11 extended in a certain predetermined direction has a branch flow path 12 in the middle, and an arrow 13 indicates the direction of the flow of fluid introduced into the flow path 11. Arrows 14 and 15 indicate the direction of the flow of fluid introduced into the branch flow path 12 and the direction of the flow of fluid introduced downstream of the flow path 11, respectively. A dotted line 16 represents the boundary between the fluid portion introduced into the branch flow channel 12 and the fluid portion introduced downstream of the flow channel 11. The channel A in the claims is the channel 11, and the branch point in the channel A is the branch point 17.

流路11に大きな粒子と小さな粒子を懸濁させた流体を連続的に導入する。分岐流路12へ導入される流量がある値より小さければ、流路11の壁近傍を流れる小さな粒子のみが分岐流路12へ導入され、大きな粒子はその径が分岐流路12の流路幅より小さくても分岐流路12へは導入されず、流路11の下流に導入される。つまり、分岐流路12からはある大きさ以上の粒子を含まない流体を回収することができる。  A fluid in which large particles and small particles are suspended is continuously introduced into the flow path 11. If the flow rate introduced into the branch channel 12 is smaller than a certain value, only small particles flowing in the vicinity of the wall of the channel 11 are introduced into the branch channel 12, and the larger particles have a diameter of the channel width of the branch channel 12. Even if it is smaller, it is not introduced into the branch channel 12 but is introduced downstream of the channel 11. That is, a fluid that does not contain particles of a certain size or more can be recovered from the branch flow path 12.

また、図1(b)のように流路11に分岐流路を複数設け、粒子を含まない流体(流体18)と粒子を懸濁させた流体(流体19)を流路11に導入し、各々の流路に導入する流量を調節することにより、多段階での分離・濃縮が可能となる。ここで、流体18と流体19の境界を点線23で表す。  Further, as shown in FIG. 1B, a plurality of branch channels are provided in the channel 11, and a fluid not containing particles (fluid 18) and a fluid in which particles are suspended (fluid 19) are introduced into the channel 11, By adjusting the flow rate introduced into each channel, separation / concentration in multiple stages becomes possible. Here, the boundary between the fluid 18 and the fluid 19 is represented by a dotted line 23.

なお、この場合は流路11の下側に分岐流路を設けたが、当然上側、あるいは紙面に対して表裏のどちらか片側あるいは両側などに設けてもよい。  In this case, the branch flow path is provided below the flow path 11, but naturally, it may be provided on the upper side or on one side or both sides of the front and back of the paper.

また、流路11と分岐流路の構造を適当にデザインすることによって、流体19の流体の部分およびある一定の大きさよりも小さな粒子を分岐流路群20から全て取り除けるようにすることができ、そのようにすることによって分岐流路群20よりも下流の流路11ではある一定の大きさ以上の粒子が壁側に一列に並び、分岐流路21−aからは粒子22−aを、分岐流路21−bからは粒子22−bを、分岐流路21−cからは粒子22−cを、それぞれ全て導入前よりも濃縮した状態で回収することができる。ここで、粒子22−a、22−b、22−cはそれぞれ大きさが異なっており、22−aが一番小さく、22−cが一番大きい粒子である。  Further, by appropriately designing the structure of the flow path 11 and the branch flow path, it is possible to remove all of the fluid portion of the fluid 19 and particles smaller than a certain size from the branch flow path group 20, By doing so, particles of a certain size or more in the channel 11 downstream of the branch channel group 20 are arranged in a line on the wall side, and the particles 22-a are branched from the branch channel 21-a. The particles 22-b can be recovered from the channel 21-b, and the particles 22-c can be recovered from the branch channel 21-c in a more concentrated state than before introduction. Here, the particles 22-a, 22-b and 22-c are different in size, 22-a is the smallest and 22-c is the largest particle.

なお、各分岐流路に導入される流体の流量の調節は、流路下流においてバルブを取り付ける、流路下流の温度を調節することにより流体の粘度を変化させる、などの方法が考えられるが、流路の抵抗を考慮した流路構造をあらかじめデザインしておくことが簡単な方法である。  The flow rate of the fluid introduced into each branch channel may be adjusted by attaching a valve downstream of the channel or changing the viscosity of the fluid by adjusting the temperature downstream of the channel. It is a simple method to design a flow path structure in consideration of the resistance of the flow path in advance.

なお、図1(b)の流路構造では、濃縮した後に粒子を3回に分けて選抜する原理が示されているが、選抜するための流路(流路21−a,21−b,21−cに相当)は0本でも、1本でも、2本でも、4本以上でもよい。  The flow path structure of FIG. 1 (b) shows the principle of selecting particles in three times after concentration, but the flow paths for selection (flow paths 21-a, 21-b, (Corresponding to 21-c) may be zero, one, two, four or more.

以下、添付の書類に基づいて、本発明による微粒子を濃縮・分離する流路構造およびその方法の実施例を詳細に説明する。  Hereinafter, an embodiment of a flow channel structure and method for concentrating and separating fine particles according to the present invention will be described in detail based on the attached documents.

図2(a)(b)(c)には、本発明による微粒子を濃縮・分離する流路構造およびその方法の実施形態を備えたマイクロチップ24が示されており、図2(a)は図2(b)と(c)におけるA矢視図であり、図2(b)は図2(a)におけるB−B線による断面図であり、図2(c)は図2(a)におけるC−C線による断面図である。また、図3(a)は図2(a)における流路全体の拡大図であり、図3(b)は図3(a)の一部48−aの拡大図であり、図3(c)は図3(a)の一部48−bの拡大図である。  FIGS. 2A, 2B, and 2C show a microchip 24 that includes an embodiment of a flow channel structure for concentrating and separating fine particles according to the present invention and a method thereof, and FIG. 2 (b) and 2 (c), FIG. 2 (b) is a cross-sectional view taken along line BB in FIG. 2 (a), and FIG. 2 (c) is FIG. 2 (a). It is sectional drawing by CC line | wire in FIG. 3 (a) is an enlarged view of the entire flow path in FIG. 2 (a), FIG. 3 (b) is an enlarged view of a part 48-a of FIG. 3 (a), and FIG. ) Is an enlarged view of a part 48-b of FIG.

このマイクロチップ24は、粒子を含む流体と粒子を含まない流体を連続的に導入した際、直径約7μm以上の粒子を含まない流体と直径7μm以上の粒子を含む流体とを別々に回収すると同時に、直径が約20〜18μm,18〜15μm,15〜14μm,14〜12μm,12〜11μm,11〜10μm,10〜8μm,8〜7μmの粒子を選択的に分離・濃縮することができるマイクロチップであり、高分子材料、例えばPDMS(ポリジメチルシロキサン)により形成された2枚の平板状の基板25、基板26により形成されている。  The microchip 24 collects a fluid containing no particles having a diameter of about 7 μm or more and a fluid containing particles having a diameter of 7 μm or more separately when a fluid containing particles and a fluid containing no particles are continuously introduced. , A microchip capable of selectively separating and concentrating particles having diameters of about 20 to 18 μm, 18 to 15 μm, 15 to 14 μm, 14 to 12 μm, 12 to 11 μm, 11 to 10 μm, 10 to 8 μm, and 8 to 7 μm It is formed by two flat substrates 25 and 26 formed of a polymer material, for example, PDMS (polydimethylsiloxane).

なお、マイクロ流体デバイスの材料としてはPDMSの他にも、アクリル等の各種ポリマー材料、ガラス、シリコン、ステンレス、セラミックス、各種金属などを用いることができる。  In addition to PDMS, various polymer materials such as acrylic, glass, silicon, stainless steel, ceramics, various metals, and the like can be used as a material for the microfluidic device.

基板25の下面25−aには、流路構造が形成されており、例えばその深さは25μm程度であるが、この値は例えば0.1μmから1cmまで任意の値に設定することが可能である。  A flow path structure is formed on the lower surface 25-a of the substrate 25. For example, the depth is about 25 μm, but this value can be set to any value from 0.1 μm to 1 cm, for example. is there.

入口27は粒子を含む流体の、入口28は粒子を含まない流体の入口であり、出口29〜37は流体の出口である。  The inlet 27 is a fluid containing particles, the inlet 28 is a fluid inlet not containing particles, and the outlets 29 to 37 are fluid outlets.

また、流路38は入口27、28と出口29を結ぶ流路であり、途中、3つの幅が異なる部分38−a、38−b、38−cから成り立ち、その一部である38−bには分岐流路群39および分岐流路40〜47が存在する。なお、流路38は請求項における流路Aに相当する流路である。  The flow path 38 is a flow path connecting the inlets 27 and 28 and the outlet 29. The flow path 38 is formed by three portions 38-a, 38-b, and 38-c having different widths, and 38-b that is a part thereof. Branch channel group 39 and branch channels 40 to 47 exist. The flow path 38 corresponds to the flow path A in the claims.

なお、流路38の全体の長さは、例えば約7mmであり、部分38−a、38−b、38−cの幅は例えばそれぞれ100μm、40μm、100μmであるが、これらの値は必要に応じて1μm以上の任意の値に調節することができる。  The entire length of the flow path 38 is, for example, about 7 mm, and the widths of the portions 38-a, 38-b, 38-c are, for example, 100 μm, 40 μm, and 100 μm, respectively, but these values are necessary. Accordingly, it can be adjusted to an arbitrary value of 1 μm or more.

また、出口30〜37はそれぞれ流路38−bから分岐流路40〜47を介して接続されている。さらに、それぞれの分岐流路(例えば40)は、細い部分(例えば40−a)と太い部分(例えば40−b)から成っており、それぞれの幅は30μmと60μmであり、隣り合う分岐流路の中心間距離は130μmである。また、これらの値は必要に応じていずれも1μm以上の任意の値に調節することができる。さらに、これらの流路は同じ太さでもよい。  Further, the outlets 30 to 37 are connected from the flow path 38-b via the branch flow paths 40 to 47, respectively. Furthermore, each branch flow path (for example, 40) consists of a thin part (for example, 40-a) and a thick part (for example, 40-b), and each width is 30 micrometers and 60 micrometers, and adjacent branch flow paths The center-to-center distance is 130 μm. These values can be adjusted to any value of 1 μm or more as necessary. Furthermore, these flow paths may have the same thickness.

分岐流路40〜47における細い部分の長さは40−aでは1620μm、47−aでは15000μmというように、出口40から47に近づくにつれて長くなるように設計されている。この設計により分岐流路40には直径約18〜20μmの粒子が、分岐流路41には直径約15〜18μmの粒子が、分岐流路42には直径約14〜15μmの粒子が、分岐流路43には直径約12〜14μmの粒子が、分岐流路44には直径約11〜12μmの粒子が、分岐流路45には直径約10〜11μmの粒子が、分岐流路46には直径約8〜10μmの粒子が、分岐流路47には直径約7〜8μmの粒子がそれぞれ選抜されるようになっているが、これらの値は必要に応じて1μm以上の任意の値に調節することができる。  The length of the narrow part in the branch flow paths 40 to 47 is designed to become longer as it approaches the outlet 40 from the outlet 40, such as 1620 μm for 40-a and 15000 μm for 47-a. With this design, particles having a diameter of about 18 to 20 μm are supplied to the branch flow channel 40, particles having a diameter of about 15 to 18 μm are supplied to the branch flow channel 41, and particles having a diameter of about 14 to 15 μm are supplied to the branch flow channel 42. Particles with a diameter of about 12-14 μm are in the channel 43, particles with a diameter of about 11-12 μm are in the branch channel 44, particles with a diameter of about 10-11 μm are in the branch channel 45, and diameters are in the branch channel 46. Particles having a diameter of about 8 to 10 μm and particles having a diameter of about 7 to 8 μm are selected in the branch channel 47. These values are adjusted to an arbitrary value of 1 μm or more as necessary. be able to.

また、分岐流路群39は、それぞれ長さ18mmである40本の分岐流路(39−1〜39−40)から成り、マイクロチップ24の側面において外部に開放されている。また、これらの長さは1μm以上の任意の値に調節することができ、本数も40本より少なくても多くてもよい。  The branch channel group 39 includes 40 branch channels (39-1 to 39-40) each having a length of 18 mm, and is open to the outside on the side surface of the microchip 24. Moreover, these lengths can be adjusted to an arbitrary value of 1 μm or more, and the number may be less or more than 40.

また、それぞれの分岐流路(例えば39−40)は、細い部分(例えば39−40−a)と太い部分(例えば39−40−b)からなっており、それぞれの幅は20μmと40μmであり、隣り合う分岐流路の中心間距離は70μmである。また、これらの値も1μm以上の任意の値に調節することができ、さらに、これらの流路は同じ太さでもよい。  Each branch channel (for example, 39-40) is composed of a thin part (for example, 39-40-a) and a thick part (for example, 39-40-b), and the respective widths are 20 μm and 40 μm. The distance between the centers of the adjacent branch channels is 70 μm. Moreover, these values can also be adjusted to arbitrary values of 1 μm or more, and these flow paths may have the same thickness.

分岐流路39−1〜39−40における幅が細い部分の長さは、39−1−aでは約14000μm、39−40−aでは約9000μmというように、39−1−aから39−40−aへ徐々に長くなるように設計されている。この設計により、40個の分岐点において、それぞれの分岐点を通過する流体の約2%ずつを分岐流路群39の分岐流路一つ一つに導入することが可能である。  The lengths of the narrow portions of the branch flow paths 39-1 to 39-40 are 39-1-a to 39-40, such as about 14000 μm for 39-1-a and about 9000 μm for 39-40-a. Designed to gradually increase to -a. With this design, it is possible to introduce about 2% of the fluid passing through each branch point into each branch channel of the branch channel group 39 at 40 branch points.

以上の構成において、上記したマイクロチップを用い、動植物細胞、オルガネラ、微生物、エアロゾル、セラミック粒子、ポリマー粒子、エマルション、無機粒子、金属ナノ粒子等の粒子を濃縮・分離するための方法を説明する。  A method for concentrating and separating particles such as animal and plant cells, organelles, microorganisms, aerosols, ceramic particles, polymer particles, emulsions, inorganic particles, and metal nanoparticles using the above-described microchip in the above configuration will be described.

まず、水や空気などの流体中に粒子を懸濁させたもの、あるいは、血液や、環境水などのように初めから分離対象となる粒子が懸濁している流体を用意する。  First, a fluid in which particles are suspended in a fluid such as water or air, or a fluid in which particles to be separated are suspended from the beginning, such as blood or environmental water, is prepared.

また、粒子を含まない流体を用意する。  Also, a fluid containing no particles is prepared.

そして、用意した粒子を含む流体を入口27から、粒子を含まない流体を入口28からそれぞれマイクロチップ24内に連続的に導入する。この際、流路内における流体の流れはできるだけ層流の状態を保ったまま導入する方が望ましい。  The prepared fluid containing particles is continuously introduced into the microchip 24 from the inlet 27 and the fluid not containing particles is introduced into the microchip 24 from the inlet 28, respectively. At this time, it is desirable to introduce the fluid flow in the flow path while keeping the state of laminar flow as much as possible.

マイクロチップ24の流路構造に導入させた場合、出口30、31、32、33、34、35、36、37からそれぞれ約6.8%、5.2%、4.0%、3.2%、2.4%、2.0%、1.6%、1.2%の流体が流出することが期待されている。  When introduced into the channel structure of the microchip 24, the outlets 30, 31, 32, 33, 34, 35, 36, and 37 are about 6.8%, 5.2%, 4.0%, and 3.2, respectively. %, 2.4%, 2.0%, 1.6%, 1.2% of the fluid is expected to flow out.

実際に、3μmと5μmの蛍光粒子をデキストラン溶液5wt%に懸濁させたものと、デキストラン溶液5wt%を、シリンジポンプを用いてそれぞれ入口27、28からマイクロチップ24に流量20μL/minで連続的に導入したところ、どちらの粒子もほぼ100%分岐流路群39へ導入されることが確認された。  Actually, 3 μm and 5 μm fluorescent particles suspended in 5 wt% of dextran solution and 5 wt% of dextran solution were continuously fed from the inlets 27 and 28 to the microchip 24 using a syringe pump at a flow rate of 20 μL / min. As a result, it was confirmed that almost 100% of both particles were introduced into the branch channel group 39.

なお、デキストラン溶液でなくてもよい。また、血液を希釈して導入すると、赤血球と白血球を分離し、さらに白血球を種類ごとに分離して、回収できる。  The dextran solution may not be used. Moreover, when blood is diluted and introduced, red blood cells and white blood cells can be separated, and further, the white blood cells can be separated and collected for each type.

マイクロチップ24では、入り口を2つ作ることにより、粒子を含む流体と粒子を含まない流体を使用し、それぞれの部分に分けたが、図4に示すマイクロチップ49のような構造を用いると、粒子を含む流体のみを流路内に導入するだけで、流路の途中において、粒子を含む流体の部分と粒子を含まない流体の部分に分けて導入することができ、複数の入口を設け、粒子を含む流体と含まない流体をそれぞれ導入するのと同様の効果を得ることができる。  In the microchip 24, by using two inlets, a fluid containing particles and a fluid not containing particles are used and divided into respective parts. However, when a structure like the microchip 49 shown in FIG. 4 is used, By only introducing a fluid containing particles into the flow channel, it can be divided into a fluid portion containing particles and a fluid portion not containing particles in the middle of the flow channel, and a plurality of inlets are provided. An effect similar to that of introducing a fluid containing particles and a fluid not containing particles can be obtained.

また、マイクロチップ24のような構造において、入口は2つ以上でもよく、マイクロチップ49のような構造においては、入口は1つ以上でもよい。  In the structure such as the microchip 24, the number of inlets may be two or more. In the structure such as the microchip 49, one or more inlets may be used.

図4(a)は、図4の(b)(c)におけるA矢視図であり、図4(b)は図4(a)におけるB−B線による断面図であり、図4(c)は図4(a)におけるC−C線による断面図である。  4 (a) is a view taken along arrow A in FIGS. 4 (b) and 4 (c), FIG. 4 (b) is a cross-sectional view taken along line BB in FIG. 4 (a), and FIG. ) Is a cross-sectional view taken along the line CC in FIG.

マイクロチップ49は、入り口52から粒子を含む流体を導入した際、直径1.0μm以上の粒子を含む流体と直径1.0μm以上の粒子を含まない流体に分離することができ、さらに、直径約1.0〜1.5μm、1.5〜2.0μm、2.0〜2.5μmの粒子をそれぞれ選択的に分離・濃縮することができるマイクロチップである。  When a fluid containing particles is introduced from the inlet 52, the microchip 49 can be separated into a fluid containing particles having a diameter of 1.0 μm or more and a fluid not containing particles having a diameter of 1.0 μm or more. It is a microchip capable of selectively separating and concentrating particles of 1.0 to 1.5 μm, 1.5 to 2.0 μm, and 2.0 to 2.5 μm.

流路構造は、基板50の下面50−aに形成されており、その深さは例えば5μm程度である。この値は、0.1μm以上の任意の値に調節することができる。  The channel structure is formed on the lower surface 50-a of the substrate 50, and the depth thereof is, for example, about 5 μm. This value can be adjusted to an arbitrary value of 0.1 μm or more.

流路53は、出口56、57、58、59を有しており、入口52は粒子を含む流体を導入するための入り口である。  The channel 53 has outlets 56, 57, 58, 59, and the inlet 52 is an inlet for introducing a fluid containing particles.

流路53は、5つの幅の異なる部分53−a〜eから成り立ち、その一部53−bと53−cは分岐流路群54を共有しており、53−dは分岐流路群55および分岐流路60〜62を有する。  The flow channel 53 includes five portions 53-a to e having different widths, and the portions 53-b and 53-c share the branch flow channel group 54, and 53-d indicates the branch flow channel group 55. And branch passages 60-62.

分岐流路群54は、50本の分岐流路から成り立ち、流路53−bと流路53−cを結ぶような構造をしているが、この本数は1本以上の任意の数に調整できる。また、分岐流路群54は、1.0μm以上の粒子を含まない流体が導入されるように設計されている。  The branch channel group 54 is composed of 50 branch channels and has a structure connecting the channel 53-b and the channel 53-c. The number is adjusted to an arbitrary number of one or more. it can. The branch channel group 54 is designed so that a fluid not containing particles of 1.0 μm or more is introduced.

分岐流路群55は、長さ25mmである80本の分岐流路から成り立ち、マイクロチップ49の側面において外部に開放されているが、必要に応じて80本以上でも以下でもよい。また、分岐流路群55は、1.0μm以上の粒子を含まない流体が導入されるように設計されている。  The branch channel group 55 is composed of 80 branch channels having a length of 25 mm, and is open to the outside on the side surface of the microchip 49, but may be 80 or more or less as required. The branch channel group 55 is designed so that a fluid not containing particles of 1.0 μm or more is introduced.

それぞれ出口57、58、59につながる流路60、61、62は、径が1.0〜1.5μm、1.5〜2.0μm、2.0〜2.5μmの粒子が選択的に導入されるように設計されている。これにより、それぞれの出口から、それぞれの大きさの粒子を濃縮した形で回収することが可能である。  The channels 60, 61, 62 connected to the outlets 57, 58, 59, respectively, selectively introduce particles having a diameter of 1.0 to 1.5 μm, 1.5 to 2.0 μm, and 2.0 to 2.5 μm. Designed to be. Thereby, it is possible to collect | recover the particle | grains of each magnitude | size in the concentrated form from each exit.

また、図4に示すようなデザイン以外にも、図5(a)(b)(c)に示すようなデザインであっても同様の効果を得ることができる。  In addition to the design shown in FIG. 4, the same effect can be obtained with the design shown in FIGS. 5A, 5 </ b> B, and 5 </ b> C.

図5(d)は、遠心力、電場あるいは磁場などのマイクロデバイスの外部からの力を用いる場合のデバイスの例である。この場合、流路のうち少なくとも1部分に矢印63の向きに遠心場、磁場や電場を加えることにより、粒子を含む流体の部分と粒子を含まない流体の部分に分けて導入することができるため、入口を2つ以上設けた場合や流れの分割、統合を利用した場合と同様の効果を得ることができる。  FIG. 5D shows an example of a device in the case of using a force from the outside of the microdevice such as a centrifugal force, an electric field, or a magnetic field. In this case, since a centrifugal field, a magnetic field, or an electric field is applied to at least one portion of the flow path in the direction of the arrow 63, the fluid can be introduced separately into the fluid portion containing particles and the fluid portion not containing particles. The same effect can be obtained as when two or more inlets are provided, or when flow division or integration is used.

また、図6(a)(b)(c)(d)(e)(f)に示すように、分岐流路群を太く長い流路につなげ、1つの出口から流体を排出できるようなデザインを用いてもよい。ここで、図6(a)は粒子を含む流体と粒子を含まない流体を連続的に導入するデバイスであり、図6(b)〜(e)は粒子を含む流体のみを連続的に導入するデバイスであり、図6(f)は粒子を含む流体のみを連続的に導入し、さらに遠心場、磁場や電場をかけるデバイスである。  Also, as shown in FIGS. 6 (a), (b), (c), (d), (e), and (f), the branch channel group is connected to a thick and long channel so that fluid can be discharged from one outlet. May be used. Here, FIG. 6A is a device that continuously introduces a fluid containing particles and a fluid that does not contain particles, and FIGS. 6B to 6E continuously introduce only a fluid containing particles. FIG. 6F shows a device in which only a fluid containing particles is continuously introduced, and a centrifugal field, a magnetic field, and an electric field are further applied.

本発明に記載の微粒子の濃縮・分級のための流路構造およびその方法を用いると、例えば集塵装置として、医療分野においては血液検査の際に、または、水質検査において、水中に僅かしか含まれない菌や微生物を調査する際に利用可能である。  When the flow path structure for concentration / classification of fine particles described in the present invention and the method thereof are used, for example, as a dust collector, in the blood field in the medical field, or in the water quality test, a small amount is contained in the water. It can be used when investigating germs and microorganisms that are not.

本発明に記載の微粒子の濃縮・分級のための流路構造およびその方法を用いると、例えば複雑な細胞集団の中に含まれる極わずかな、形態の異なる細胞を、複雑な装置を用いずに、濃縮・分離・選抜することができ、生化学や医療などにおいて極めて有効である。  When the flow channel structure and method for concentration / classification of microparticles described in the present invention are used, for example, very few cells with different morphologies contained in a complex cell population can be obtained without using a complex device. It can be concentrated, separated and selected, and is extremely effective in biochemistry and medicine.

さらに本発明に記載の微粒子の濃縮・分級のための流路構造およびその方法を用いると、環境水中にわずかに含まれる微生物の濃縮・分級や、合成されたポリマー粒子の分離、またエマルションのようなやわらかい粒子の濃縮・分級も可能になり、非常に有用である。  Furthermore, when the flow path structure and method for concentration / classification of fine particles described in the present invention are used, concentration / classification of microorganisms slightly contained in environmental water, separation of synthesized polymer particles, and emulsion It is possible to concentrate and classify soft particles, which is very useful.

また、本発明に記載の微粒子の濃縮・分級のための流路構造およびその方法を用いると、空気中のエアロゾル、花粉、ハウスダスト等の微粒子を、効率的に分離、回収することができ、非常に有用である。  In addition, by using the flow path structure for concentration and classification of fine particles described in the present invention and the method thereof, fine particles such as aerosol, pollen, house dust, etc. in the air can be efficiently separated and recovered, Very useful.

本発明による微粒子の濃縮・分級のための流路構造およびその方法の原理図を示している。FIG. 1 shows a principle diagram of a flow channel structure and method for concentration and classification of fine particles according to the present invention. 本発明による微粒子の濃縮・分級の実施形態を備えたマイクロチップ21を示し、図2(a)は図2(b)と(c)におけるA矢視図であり、図2(b)は図2(a)におけるB−B線による断面図であり、図2(c)は図2(a)におけるC−C線による断面図である。2 shows a microchip 21 equipped with an embodiment for concentrating and classifying microparticles according to the present invention, in which FIG. 2 (a) is a view taken in the direction of arrow A in FIGS. 2 (b) and 2 (c), and FIG. 2A is a cross-sectional view taken along line BB in FIG. 2A, and FIG. 2C is a cross-sectional view taken along line CC in FIG. 2A. また、図3(a)は図2(a)における流路全体の拡大図であり、図3(b)は図3(a)の一部45−aの拡大図であり、図3(b)は図3(c)の一部45−bの拡大図である。3 (a) is an enlarged view of the entire flow path in FIG. 2 (a), FIG. 3 (b) is an enlarged view of a part 45-a of FIG. 3 (a), and FIG. ) Is an enlarged view of a part 45-b of FIG. 本発明による微粒子の濃縮・分級の実施形態を備えたマイクロチップ58を示し、図4(a)は図4(b)と(c)におけるA矢視図であり、図4(b)は図4(a)におけるB−B線による断面図であり、図4(c)は図4(a)におけるC−C線による断面図である。また、図4(d)は図4(a)における流路全体の拡大図である。4 shows a microchip 58 equipped with an embodiment of fine particle concentration / classification according to the present invention, FIG. 4 (a) is a view taken along arrow A in FIG. 4 (b) and FIG. 4 (c), and FIG. 4A is a cross-sectional view taken along line BB in FIG. 4A, and FIG. 4C is a cross-sectional view taken along line CC in FIG. Moreover, FIG.4 (d) is an enlarged view of the whole flow path in Fig.4 (a). 図5(a)(b)(c)は、本発明による微粒子の濃縮・分級における、迂回流路を用いた流路構造の例であり、(d)は遠心場、電場、磁場などの力を用いて微粒子を分離・濃縮するための流路構造の例である。FIGS. 5A, 5B, and 5C are examples of a channel structure using a bypass channel in the concentration and classification of fine particles according to the present invention, and FIG. 5D is a force such as a centrifugal field, an electric field, and a magnetic field. It is an example of the flow-path structure for isolate | separating and concentrating microparticles | fine-particles. 図6(a)(b)(c)(d)(e)は、本発明による微粒子の濃縮・分級における、分岐流路群をまとめて1つの出口につなげた流路構造の例である。6 (a), (b), (c), (d), and (e) are examples of a channel structure in which branch channel groups are collectively connected to one outlet in the concentration / classification of fine particles according to the present invention.

符号の説明Explanation of symbols

11:流路
12:分岐流路
13:流体の流れの方向
14:流体の流れの方向
15:流体の流れの方向
16:流体境界
17:分岐点
18:流体の一部
19:流体の一部
20:分岐流路群
21:分岐流路
22:粒子
23:流体境界
24:マイクロデバイス
25:基板
26:基板
27:入口
28:入口
29:出口
30:出口
31:出口
32:出口
33:出口
34:出口
35:出口
36:出口
37:出口
38:流路
39:分岐流路群
40:分岐流路
41:分岐流路
42:分岐流路
43:分岐流路
44:分岐流路
45:分岐流路
46:分岐流路
47:分岐流路
48:デバイスの一部
49:マイクロデバイス
50:基板
51:基板
52:入口
53:流路
54:分岐流路群
55:分岐流路群
56:出口
57:出口
58:出口
59:出口
60:分岐流路
61:分岐流路
62:分岐流路
63:外部からの遠心力、電場あるいは磁場等の力の方向
11: Channel 12: Branch channel 13: Fluid flow direction 14: Fluid flow direction 15: Fluid flow direction 16: Fluid boundary 17: Branch point 18: Fluid part 19: Fluid part 20: Branch channel group 21: Branch channel 22: Particle 23: Fluid boundary 24: Micro device 25: Substrate 26: Substrate 27: Inlet 28: Inlet 29: Outlet 30: Outlet 31: Outlet 32: Outlet 33: Outlet 34 : Outlet 35: outlet 36: outlet 37: outlet 38: channel 39: branch channel group 40: branch channel 41: branch channel 42: branch channel 43: branch channel 44: branch channel 45: branch flow Channel 46: Branch channel 47: Branch channel 48: Part of device 49: Micro device 50: Substrate 51: Substrate 52: Inlet 53: Channel 54: Branch channel group 55: Branch channel group 56: Outlet 57 : Outlet 58: outlet 59: outlet 60: branch channel 61:岐流 path 62: branch flow path 63: the direction of the centrifugal force, electric or power of the magnetic field or the like from the outside

Claims (11)

所定の方向に延長される流路Aと、流路Aの側面における1つ以上の分岐点と、前記分岐点において前記流路Aに接続され、長さ、幅、深さ、径などのスケールのうちいずれか1つ以上が適当に調節された分岐流路を1つ以上有する流路構造を用い、
前記流路Aの一端から、流体を連続的に導入する際、粒子を含む流体の部分と粒子を含まない流体の部分に分かれるように導入することにより、
前記分岐点において、ある一定の大きさ以上の粒子は前記分岐点において前記分岐流路に導入されないようにすることができ、ある一定の大きさ以下の粒子は前記流路Aの下流へと導入されないようにすることができるため、
導入した全てのある一定の大きさ以下の粒子を含む流体、もしくはある一定の大きさ以上の粒子を全く含まない流体を前記分岐流路から回収することができ、ある大きさ以上の粒子の濃度が高くなった流体を前記流路Aの下流から回収することができる、
微粒子の濃縮・分級のための流路構造およびその方法。
A channel A extending in a predetermined direction, one or more branch points on the side surface of the channel A, and a scale such as a length, a width, a depth, and a diameter connected to the channel A at the branch point A flow path structure having one or more branch flow paths in which at least one of them is appropriately adjusted,
When the fluid is continuously introduced from one end of the flow path A, by introducing the fluid so as to be separated into a fluid portion containing particles and a fluid portion not containing particles,
At the branch point, particles having a certain size or larger can be prevented from being introduced into the branch channel at the branch point, and particles having a certain size or smaller are introduced downstream of the channel A. Because it can be prevented from
All the introduced fluids containing particles of a certain size or less, or fluids containing no particles of a certain size or more, can be recovered from the branch flow path, and the concentration of particles of a certain size or more can be recovered. Can be recovered from the downstream of the flow path A,
Flow path structure and method for concentration and classification of fine particles.
所定の方向に延長される流路Aと、流路Aの側面における複数の分岐点と、前記複数の分岐点それぞれにおいて前記流路Aに接続され、長さ、幅、深さ、径などのスケールのうちいずれか1つ以上が適当に調節された分岐流路を1つ以上有する流路構造を用い、
前記流路Aの一端から、流体を連続的に導入する際、粒子を含む流体の部分と粒子を含まない流体の部分に分かれるように導入することにより、
前記複数の分岐点のうちの少なくとも1つの分岐点において、ある一定の大きさ以上の粒子は前記分岐点において前記分岐流路に導入されないようにすることができ、ある一定の大きさ以下の粒子は前記流路Aの下流へと導入されないようにすることができ、また前記複数の分岐点のうちの少なくとも1つの分岐点において、ある一定の大きさ以上の粒子が前記分岐点において前記分岐流路に導入されるようにすることができるため、
導入した全てのある一定の大きさ以上の粒子は前記流路Aの壁側近傍に濃縮され、さらに、前記複数の分岐流路のいくつかから濃縮された粒子を回収することができる、
微粒子の濃縮・分級のための流路構造およびその方法。
A channel A extending in a predetermined direction, a plurality of branch points on the side surface of the channel A, and connected to the channel A at each of the plurality of branch points, such as length, width, depth, diameter, etc. Using a flow path structure having one or more branch flow paths in which at least one of the scales is appropriately adjusted,
When the fluid is continuously introduced from one end of the flow path A, by introducing the fluid so as to be separated into a fluid portion containing particles and a fluid portion not containing particles,
In at least one of the plurality of branch points, particles having a certain size or more can be prevented from being introduced into the branch channel at the branch point, and particles having a certain size or less. Can be prevented from being introduced downstream of the flow path A, and at least one of the plurality of branch points, particles having a certain size or more may flow at the branch point. Can be introduced to the road,
All the particles having a certain size or more introduced are concentrated near the wall side of the flow path A, and further, the concentrated particles can be recovered from some of the plurality of branch flow paths.
Flow path structure and method for concentration and classification of fine particles.
請求項1または請求項2のいずれか1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、
前記流路Aの途中に存在する前記分岐流路は、前記流路Aの片側断面のみに存在する、
微粒子の濃縮・分級のための流路構造およびその方法。
In the flow path structure and method for concentration / classification of fine particles according to any one of claims 1 and 2,
The branch flow channel existing in the middle of the flow channel A exists only in one side cross section of the flow channel A.
Flow path structure and method for concentration and classification of fine particles.
請求項1、請求項2または請求項3のいずれか1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、
前記流路Aに流体を連続的に導入する際、粒子を含む流体の部分と粒子を含まない流体の部分に分かれるように流体を導入する方法として、
入り口を複数個設け、少なくとも1つの入り口から粒子を含む流体を、少なくとも1つの入り口から粒子を含まない流体を導入する、
微粒子の濃縮・分級のための流路構造およびその方法。
In the flow path structure and method for concentration / classification of fine particles according to any one of claims 1, 2, or 3,
When the fluid is continuously introduced into the flow path A, as a method of introducing the fluid so as to be divided into a fluid portion containing particles and a fluid portion not containing particles,
Providing a plurality of inlets, introducing a fluid containing particles from at least one inlet, and introducing a fluid not containing particles from at least one inlet;
Flow path structure and method for concentration and classification of fine particles.
請求項3に記載の微粒子の濃縮・分級のための流路構造およびその方法において、
前記流路Aに流体を連続的に導入する際、粒子を含む流体の部分と粒子を含まない流体の部分に分けて流体を導入する方法として、
前記流路Aに、入口と前記分岐流路との間において一度前記流路Aから分岐し、かつ前記分岐流路よりも上流において再び前記流路Aに接続される分岐流路(迂回流路とする)を1つ以上設け、粒子を含む流体を入り口から導入させることにより、
ある一定の大きさ以上の粒子を含まない流体、あるいは粒子を全く含まない流体を迂回流路に導入し、前記分岐流路よりも上流で再び前記流路Aに導入する、
微粒子の濃縮・分級のための流路構造およびその方法。
In the flow channel structure and method for concentration and classification of fine particles according to claim 3,
When a fluid is continuously introduced into the flow path A, as a method of introducing the fluid separately into a fluid portion containing particles and a fluid portion not containing particles,
A branch channel (a bypass channel) that once branches from the channel A to the channel A between the inlet and the branch channel and is connected to the channel A again upstream of the branch channel. And by introducing a fluid containing particles from the entrance,
Introducing a fluid that does not contain particles of a certain size or more, or a fluid that does not contain any particles, into the bypass channel, and introduces the fluid again into the channel A upstream from the branch channel;
Flow path structure and method for concentration and classification of fine particles.
請求項3に記載の微粒子の濃縮・分級のための流路構造およびその方法において、
前記流路Aに流体を連続的に導入する際、粒子を含む流体の部分と粒子を含まない流体の部分に分けて流体を導入する方法として、
前記流路構造に遠心力、電場あるいは磁場を与える、
微粒子の濃縮・分級のための流路構造およびその方法。
In the flow channel structure and method for concentration and classification of fine particles according to claim 3,
When a fluid is continuously introduced into the flow path A, as a method of introducing the fluid separately into a fluid portion containing particles and a fluid portion not containing particles,
Apply centrifugal force, electric field or magnetic field to the channel structure,
Flow path structure and method for concentration and classification of fine particles.
請求項1、請求項2、請求項3、請求項4、請求項5または請求項6のいずれか1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、
前記流路の幅、深さ、径のいずれかのスケールが、少なくとも部分的に1センチメートル以下のオーダーであり、前記流路内における流体の流れは少なくとも部分的に安定した層流になる、
微粒子の濃縮・分級のための流路構造およびその方法。
In the flow path structure and method for fine particle concentration / classification according to any one of claims 1, 2, 3, 4, 4, 5 or 6,
The scale of any of the width, depth, and diameter of the flow path is at least partially on the order of 1 centimeter or less, and the fluid flow in the flow path is at least partially stable laminar flow,
Flow path structure and method for concentration and classification of fine particles.
請求項1、請求項2、請求項3、請求項4、請求項5、請求項6または請求項7のいずれか1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、
流体とは液体である、
微粒子の濃縮・分級のための流路構造およびその方法。
In the flow path structure and method for fine particle concentration / classification according to any one of claims 1, 2, 3, 4, 5, 6, and 7. ,
Fluid is liquid,
Flow path structure and method for concentration and classification of fine particles.
請求項1、請求項2、請求項3、請求項4、請求項5、請求項6または請求項7のいずれか1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、
流体とは気体である、
微粒子の濃縮・分級のための流路構造およびその方法。
In the flow path structure and method for fine particle concentration / classification according to any one of claims 1, 2, 3, 4, 5, 6, and 7. ,
A fluid is a gas,
Flow path structure and method for concentration and classification of fine particles.
請求項1、請求項2、請求項3、請求項4、請求項5、請求項6、請求項7、請求項8または請求項9のいずれかの1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、
粒子とは細胞である、
微粒子の濃縮・分級のための流路構造およびその方法。
The concentration / classification of fine particles according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, or 9. In a flow channel structure and method therefor,
A particle is a cell,
Flow path structure and method for concentration and classification of fine particles.
請求項1、請求項2、請求項3、請求項4、請求項5、請求項6、請求項7、請求項8、請求項9または請求項10のいずれかの1項に記載の微粒子の濃縮・分級のための流路構造およびその方法において、
前記流路とはマイクロチップ内に形成されたマイクロチャネルである、
微粒子の濃縮・分級のための流路構造およびその方法。
The fine particles according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In the flow path structure and method for concentration and classification,
The flow path is a microchannel formed in a microchip.
Flow path structure and method for concentration and classification of fine particles.
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