JP2004122107A - Microchannel structure, method for producing fine particle using the same and method for extracting solvent using the microchannel structure - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a microchannel structure capable of producing fine particles, responding to industrial mass production, hardening the fine particles immediately after producing them without breaking the shapes of the produced fine particles and separating the fine particles from the medium, a method for producing the fine particles using the microchannel structure, and to provide a method for extracting a solvent using the microchannel structure. <P>SOLUTION: The microchannel structure comprises a microchannel provided with an introducing port and an introducing channel for introducing a dispersion phase, an introducing port and an introducing channel for introducing a continuous phase, and a discharging port and a discharging channel for discharging the fine particles produced by the dispersion phase and the continuous phase. The dispersion phase introducing channel and the continuous phase introducing channel intersect at an arbitrary angle and the two introducing channels are connected to the discharging channel at an arbitrary angle. <P>COPYRIGHT: (C)2004,JPO

Description

また、一方の共通流路にポリビニルアルコールの３％水溶液を、もう一方の共通流路にジビニルベンゼン、酢酸ブチルの混合溶液を実施例１と同様な方法で１００μｌ／ｍｉｎで送液し、各微小流路で生成した１０個の微小粒子の粒径を顕微鏡により測定し平均した結果、表２に示す結果が得られ、各微小流路より排出された微小粒子の粒径の平均値が１０１．０μｍ、粒径の分散度を示すＣＶ値（％）は８．７％となり、各微小流路で均一な微小粒子を生成することができた。
【００９１】
【表２】

（比較例２）
第２の比較例として、図３１に示すような微小流路（１６）を有する微小流路構造体を製作した。流路深さが８０μｍで流路幅が共通流路導入口（３２）の位置で２ｍｍ、共通流路排出口（３１）の位置で０．５ｍｍになるように、共通流路導入口の位置から共通流路排出口の位置にむけて徐々に流路幅を狭くしたの２本の共通流路（２９）から幅２２０μｍ、深さ８０μｍの微小流路を引き出してＹ字状に合流させた微小流路４本を、６ｍｍの等間隔（ａ_１〜ａ_５がすべて６ｍｍ）で配置した。この微小流路の形状は実施例１と同じである。共通流路導入口は、幅０．５ｍｍ、深さ８０μｍとし、共通流路排出口は、幅２２０μｍ、深さ８０μｍとした。この微小流路を有する微小流路構造体は実施例１と同様な方法で製作した。
【００９２】
この微小流路構造体の２本の共通流路のそれぞれの流体導入口に、実施例１と同様に送液ポンプを使用して、各共通流路に流速２．５ｍｌ／分で純水を５分間送液し、Ｙ字状の微小流路を通過して微小流路の流体排出口から排出された液量を各流路で比較したところ、表１に示す結果が得られ、Ｙ_１〜Ｙ_４の各微小流路に均一に液体を送液することができなかった。
【００９３】
また、一方の共通流路にポリビニルアルコールの３％水溶液を、もう一方の共通流路にジビニルベンゼン、酢酸ブチルの混合溶液をそれぞれ実施例１と同様に送液ポンプで１００μｌ／ｍｉｎで送液し、各微小流路で生成した１０個の微小粒子の粒径を顕微鏡により測定し平均した結果、表２に示す結果が得られ、各微小流路で均一な粒径をもつ微小粒子を生成することができなかった。
【００９４】
（実施例８）
第８の実施例として、図２０に示すような微小流路を有する微小流路構造体を製作した。形成した微小流路の幅Ｗは２２０［μｍ］、微小流路の深さｄは８０［μｍ］、微小流路の長さは３０［ｍｍ］であり、導入口（１１）とつながる２本の導入流路（４８）は、４４°の角度で合流させた。この微小流路を有する微小流路構造体は、実施例１と同様な方法で製作した。
【００９５】
実施例１と同様な方法で、この微小流路の流体導入口の一方からフェノールを被抽出物質として含有した水相を送液し、もう一方の流体導入口からは、抽出溶媒として酢酸エチルの有機相を送液した。送液速度を調整することで、層流を形成して酢酸エチル側にフェノールを抽出した場合と、水相により酢酸エチルの有機相を微小粒子化して抽出した場合で実験を行なった。層流を形成したときの送液速度は、水相および有機相とも２０μｌ／ｍｉｎであった。また水相によりジビニルベンゼンの有機相を微小粒子化した場合の送液速度は、水相および有機相とも２μｌ／ｍｉｎであった。
【００９６】
この微小流路では、層流を形成した場合に得られる比界面積は、微小流路の幅Ｗが約２２０［μｍ］であることから、２×１０^４／Ｗ［ｃｍ^−１］＝約２×１０^４／２２０［ｃｍ^−１］＝約９０［ｃｍ^−１］となった。また、水相により酢酸エチルの有機相を微小粒子化した場合の微小粒子の平均粒径を高速カメラを用いて測定し、微小粒子の直径Ｄを求めたところ約２００［μｍ］であった。この場合の比界面積は、６×１０^４／Ｄ［ｃｍ^−１］＝約６×１０^４／２００［ｃｍ^−１］＝約３００［ｃｍ^−１］となった。このことから水相により酢酸エチルの有機相を微小粒子化した場合の方が、水相と有機相で層流を形成した場合よりも非界面積が大きくなり、抽出効率が上がるものと推定される。
【００９７】
実際に、流体排出口から排出された流体を試験管で回収し、有機相のみを取出して高速液体クロマトグラフィーを用いてフェノールの濃度を測定した。有機相と水相が接している時間が長いほど、抽出される物質の量が多くなることから、測定結果を抽出溶媒である有機相の送液速度から計算される微小流路内滞在時間で割り算して補正した。その結果、酢酸エチルの有機相を微小粒子化して抽出した場合のほうがフェノールの濃度が高かった。以上のことから、抽出溶媒を微小粒子化することで、抽出効率が微小流路の幅で決まる効率以上に向上したことを確認した。
【００９８】
【発明の効果】
本発明の微小粒子製造方法は、分散相と連続相を微小流路を有する微小流路構造体へその導入流路より導入し、両者が合流する合流部で分散相を連続相でせん断し微小粒子を生成させるものであり、分散相を導入するための導入流路と連続相を導入するための導入流路とが交わる角度を変化させることで、生成する微小粒子の粒径を制御することが可能である。これは、従来の微小流路構造体を使った微小粒子の生成においては、分散相と連続相の導入速度を変えて生成させる場合よりもより制御しやすく、工業的な量産に適しており、特に、分散相の導入速度と連続相の導入速度とが実質的に同じであれば、導入装置を１個用意することで足りるなどコスト面においても優れている。従って、本発明の微小粒子製造方法により、安定した粒径の微小粒子を生成することが、連続相を過剰に供給する必要がなくなり、例えばゲル製造における連続相の低コスト化、工業的な量産が可能となる。
【００９９】
また複数の分散相及び／または連続相を導入する導入流路を設けることで、分散相及び／または連続相を複数の流体の層流、または混合液または懸濁液（エマルション）とすることができ、このようにすることで、多層構造の微小粒子や、異なった多種の微小粒子を含有した微小粒子を形成することができ、複合マイクロカプセルや多重マイクロカプセルを生成することができる。
【０１００】
また微小流路の合流部分で生成した微小粒子が微小液滴であって微小液滴を硬化させる場合、硬化した微小粒子の粒径を均一にするために、微小液滴が排出流路を通過して排出部から出た後、微小流路構造体の排出部から微小流路構造体の外部に設けられた微小流路で連続的に逐次硬化しても良く、さらに硬化した微小粒子の粒径をより均一にするためには、微小流路の合流部分で微小液滴が生成した直後に、微小流路構造体中の微小流路すなわち排出流路で硬化してもよくこのようにすることで微小流路の合流部で生成した微小粒子が微小液滴の場合、微小流路の外部でビーカーなどに収集し、架橋重合などにより微小液滴を硬化すると、微小液滴を収集してから硬化するまでに、微小粒子の形状が崩れたり、微小粒子同士の合一が生じるため、硬化した微小粒子の粒径のばらつきが大きくなってしまうことが無くなり、粒径が均一な微小粒子を得ることができる。また、微小液滴を硬化することにより媒体から分離することが容易になる。
また、多数の前記微小流路を並列化及び／または積層化して微小粒子を大量に生産するための形態としては、流体を導入するための導入口及び流体を排出するための排出口を備え、基板上に前記導入口及び排出口と連通する共通流路と、前記導入口及び排出口とは異なる位置で前記共通流路と連通する１以上の微小流路とを有した微小流路構造体であって、前記共通流路の断面積が導入口との連通位置より排出口との連通位置に向かって次第に大きくなるかあるいは同じである微小流路構造体とすることで微小流路構造体に平面的あるいは立体的に配置された複数の微小流路へ均一に流体を分配することが可能となる。
【０１０１】
また、本発明の微小粒子製造方法により生成される微小粒子の用途の例として、高速液体クロマトグラフィー用カラムの充填剤、シールロック剤などの接着剤、金属粒子の絶縁粒子、圧力測定フィルム、ノーカーボン（感圧複写）紙、トナー、熱膨張剤、熱媒体、調光ガラス、ギャップ剤（スペーサ）、サーモクロミック（感温液晶、感温染料）、磁気泳動カプセル、農薬、人工飼料、人工種子、芳香剤、マッサージクリーム、口紅、ビタミン類カプセル、活性炭、含酵素カプセル、ＤＤＳ（ドラッグデリバリーシステム）などのマイクロカプセルやゲルが挙げられる。
【０１０２】
また、本発明の微小流路構造体を用いた溶媒抽出方法は、微小粒子を微小流路内での溶媒抽出に用いることにより、反応や抽出の効率を微小流路の幅で決定される効率以上に向上させることができる。
【図面の簡単な説明】
【図１】従来の微小粒子を生成する微小流路を示す概略図であり、図１右は、図１左のＡ−Ａ’、Ｂ−Ｂ’のＡ−Ａ’　断面図、Ｂ−Ｂ’断面図である。
【図２】図２（ａ）はＹ字状微小流路内における層流を示す概念図であり、図２（ｂ）は図２（ａ）の一部である円内を拡大した立体断面図である。
【図３】微小流路の合流部近傍において連続相が分散相をせん断して微小粒子を形成する方法を示す概念図である。
【図４】微小流路の合流部近傍において両側の連続相が中央の分散相を挟み込むようにをせん断して微小粒子を形成する方法を示す概念図である。
【図５】微小流路の合流部近傍において中央の連続相が両側の分散をせん断して微小粒子を形成する方法を示す概念図である。
【図６】微小流路の合流部近傍において直線状に一方の側より分散相を、もう一方の側より連続相を導入し、分散相を連続相でせん断して微小粒子を生成し、任意の方向へ排出させる方法を示す概念図である。
【図７】複数の分散相及び／または連続相を導入する分散相導入流路）及び／または連続相導入流路を設けて分散相及び／または連続相を複数の流体の層流、または混合液または懸濁液（エマルション）として、微小流路の合流部近傍において分散相を連続相でせん断して微小粒子を形成する方法を示すいくつかの概念図であり、図７（ａ）〜（ｇ）はそれぞれの態様を示す。
【図８】光照射により微小粒子を硬化させる方法を示した概略図であり、図８（ａ）は外部に光照射手段を設けた場合、図８（ｂ）はマスクを使って光照射する場合の概略図である。
【図９】加熱により微小粒子を硬化させる方法を示した概略図であり、図９（ａ）は外部に加熱手段を設けた場合、図９（ｂ）は微小流路構造体内に加熱手段を設けた場合の概略図である。
【図１０】平面的あるいは立体的に配置された複数の微小流路に均一に流体を送液する最も基本的な微小流路形状を示した概念図である。
【図１１】平面的あるいは立体的に配置された複数の微小流路に均一に流体を送液する微小流路形状のうち、共通流路の断面積が共通流路導入口から共通流路排出口に向かって次第に大きくなる例を示した概念図である。
【図１２】平面的あるいは立体的に配置された複数の微小流路に均一に流体を送液する微小流路形状のうち、２本の共通流路からＹ字上の複数の微小流路に送液した例を示した概念図である。
【図１３】平面的あるいは立体的に配置された複数の微小流路に均一に流体を送液する微小流路形状のうち、共通流路を円弧状に配置した例を示した概念図である。
【図１４】平面的あるいは立体的に配置された複数の微小流路に均一に流体を送液する微小流路形状のうち、微小流路を有する微小流路基板を重ねあわせ、共通流路を前記微小流路基板を貫通させて構成した例であり、図１４上は積層一体化を示す態様、図１４下はＤ−Ｄ’、Ｅ−Ｅ’の断面図である。
【図１５】微小流路内での微小粒子を示す概念図である。
【図１６】被抽出物質含有の流体が、原材料を有する２つの流体を別々に微小流路に導入し微小流路内の反応相で混合し反応させた流体である場合の本発明における微小粒子の用途としての溶媒抽出方法の概念図である。
【図１７】流体境界で生じる反応により生成物を生成する微小流路において、原材料を有する２つの流体を連続相とし、この連続相により流体境界で抽出溶媒をせん断することにより流体境界に微小液滴を形成し分散相とすることで、流体境界に生成した生成物を抽出する概念図である。
【図１８】被抽出物質含有の流体を微小液滴化して分散相とし、連続相である抽出溶媒に相間移動を行なって溶媒抽出を行なったあと、微小液滴の少なくとも表面を硬化することで被抽出物質を分離することを示す概念図である。
【図１９】被抽出物質含有の流体を連続相とし、微小液滴化して分散相とした抽出溶媒に相間移動を行なって溶媒抽出を行なったあと、微小液滴の少なくとも表面を硬化することで被抽出物質を分離することを示す概念図である。
【図２０】実施例１、実施例６、実施例８における微小流路を示す概略図である。
【図２１】実施例１における微小流路構造体を示す概略図である。
【図２２】実施例１における微小粒子生成法を示す概略図である。
【図２３】実施例１における微小粒子生成状況を示す概略図である。
【図２４】実施例１における生成した微小粒子を示す図である。
【図２５】実施例２における微小流路を示す概略図であり、図２５右は、図２５左のＧ−Ｇ’のＧ−Ｇ’断面図である。
【図２６】比較例１における微小流路を示す概略図であり、図２６右は、図２６左のＨ−Ｈ’のＨ−Ｈ’断面図である。
【図２７】図２７（ａ）は実施例３における微小流路を示す概略図であり、図２７（ｂ）および図２７（ｃ）は図２７（ａ）の６の部分の拡大図である。
【図２８】実施例４における微小流路を示す概略図であり、図２８右は、図２８左のＭ−Ｍ’のＭ−Ｍ’断面図である。
【図２９】実施例５における微小流路を示す概略図であり、図２９右は、図２９左のＮ−Ｎ’のＮ−Ｎ’断面図である。
【図３０】実施例７に示した微小流路形状の概略図である。
【図３１】比較例２に示した微小流路形状の概略図である。
【図３２】図３２（ａ）〜（ｅ）は、流路の底面、上面、側面のいずれか１面あるいは２面以上から１以上の突起を形成した場合の例を示すいくつかの概念図である。
【符号の説明】
１：微小流路基板
２：連続相導入口
３：連続相導入流路
４：分散相導入口
５：分散相導入流路
６：合流部
７：排出流路
８：排出口
９：微小流路の幅
１０：連続相
１１：導入口
１２：有機相
１３：水相
１４：流体境界
１５：分散相
１６：微小流路
１７：微小粒子
１８：微小粒子の直径
１９：微小流路構造体
２０：光照射スポット
２１：光照射
２２：マスク
２３：ホルダー
２４：微小流路の単位長さ
２５：微小流路の深さ
２６：ビーカー
２７：テフロン（登録商標）チューブ
２８：ヒーター
２９：共通流路
３０：カバー体
３１：共通流路排出口
３２：共通流路導入口
３３：微小液滴の直径
３４：微小液滴
３５：流体Ａ
３６：流体ｂ
３７：反応相
３８：抽出溶媒
３９：溶媒抽出
４０：フィレットジョイント
４１：マイクロシリンジポンプ
４２：マイクロシリンジ
４３：流体導入口Ａ
４４：流体導入口Ｂ
４５：流体導入口Ｃ
４６：層流流路
４７：層流合流部
４８：導入流路[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to microparticles used for column packing for preparative separation / separation, pharmaceuticals, enzyme-containing capsules, cosmetics, fragrances, display / recording materials, adhesives, microcapsules used for agricultural chemicals, etc., chemical reaction / solvent extraction The present invention also relates to a method for producing microparticles used for, for example, and its use, and relates to a microchannel structure for producing the microparticles.
[0002]
[Prior art]
In recent years, using a microchannel structure having a microchannel with a length of about several centimeters and a width and depth of sub-micrometer to several hundred micrometer on a glass substrate of several centimeters square, fluid is transferred to the microchannel. Attention has been paid to research on chemical reactions or the production of minute particles by introduction. The term “microparticles” used herein refers to not only solid microparticles, but also microdroplets, microparticles in which only the surface of the microdroplets are hardened (hereinafter referred to as “semi-hardened”), and extremely high viscosity. Also includes semi-solid fine particles. It has been suggested that such a microchannel can perform an efficient chemical reaction due to the effects of a short intermolecular distance in a microspace and a large specific interface area (for example, see Non-Patent Document 1).
[0003]
Also, by introducing two kinds of liquids having different interfacial tensions into a flow path where an intersection exists, it is possible to generate fine particles having a very uniform particle size (for example, see Non-Patent Document 2 and Patent Document 1). ). For example, as shown in FIG. 1, the method disclosed in Non-Patent Document 2 has a continuous phase introduction port (2), a continuous phase introduction channel (3), and a dispersed phase on a microchannel substrate (1). A T-shaped microchannel structure having an inlet (4), a dispersed phase inlet channel (5), an outlet channel (7), and an outlet (8). (Hereinafter, referred to as a "merging portion") has a merging portion (6). The depth of each channel is 100 μm, the width of the introduction channel for introducing the dispersed phase is 100 μm, and the width of the introduction channel for introducing the continuous phase is 300 to 500 μm. When the liquid is sent while controlling the flow rate of the continuous phase, extremely uniform fine particles can be generated at the junction. Further, it is also possible to control the particle size of the generated fine particles by controlling the flow rates of the dispersed phase and the continuous phase.
[0004]
However, in this method, the introduction flow path width of the continuous phase is 3 to 5 times wider than the introduction flow path width of the dispersed phase, and when the dispersion phase and the continuous phase are sent at the same flow rate, Since the linear velocity becomes high in the introduction flow path of the dispersed phase having a narrow flow path width, the dispersed phase and the continuous phase may become laminar in the flow after the junction, and as a result, at the junction. There was a problem that it was impossible to generate fine particles.
[0005]
For this reason, it is necessary to supply an excessive amount of the continuous phase.However, in the case of producing fine particles for industrial mass production, it is necessary to make the amount of the continuous phase excessive with respect to the amount of the dispersed phase. However, there are problems such as cost reduction and reduction of the amount of waste liquid.
[0006]
Further, with the method disclosed in Non-Patent Document 2 or Patent Document 1, it is difficult to prepare a composite capsule or a multiple capsule, and improvement thereof has been demanded.
[0007]
In addition, since the fine particles generated by the method disclosed in Non-patent Document 2 or Patent Document 1 have a relatively small variation in the particle size and are uniform, the compound forming the fine particles may be cross-linked and polymerized. It has been attempted to use the composition as a gel particle having a uniform and fine particle size used as a column packing material for fractionation and separation, etc. However, when the generated microparticles are collected in a beaker or the like outside the microchannel and the microparticles are cured by cross-linking polymerization, etc. Since the coalescence of the particles occurs, the variation in the particle size of the cured microparticles increases, and it is difficult to separate the microparticles before curing from the medium. .
[0008]
In addition, the effects of the short intermolecular distance and the large specific interface area of the above-mentioned minute space enable efficient chemical reactions to be performed, and that two kinds of liquids having different interfacial tensions are transferred to the flow path where the intersection exists. Attempts have been made to apply chemical reactions in microchannels and to apply microparticles to industrial production while taking advantage of the characteristics of microspaces that can produce extremely uniform microparticles by introducing them. Has been done. In this case, due to the small size of the micro space, the amount of generation per unit time must be reduced in a single micro channel, but if a large number of micro channels can be arranged in parallel, The generation amount per unit time can be increased while utilizing the characteristics of the road (for example, see Non-Patent Document 3). As shown in Non-Patent Document 3, it is possible to stack a microchannel substrate having a single microchannel by connecting a vertical hole penetrating a common portion such as an inlet of a reaction solution or an outlet of a reaction product. Attempted. As described above, when a large amount of chemical synthesis or generation of microparticles is performed while taking advantage of the characteristics of the microspace, the degree of integration of the microchannel, which is the minimum unit, is planarly increased or three-dimensionally stacked. Although it is said that this is possible, it has conventionally been very difficult to uniformly distribute the fluid to the microchannels arranged two-dimensionally or three-dimensionally, and improvements have been required.
[0009]
Also, Non-Patent Document 1 discloses that efficient chemical reaction can be performed without performing a special stirring operation by rapid diffusion of molecules due to a short intermolecular distance and a large specific surface area in a minute space. It has also been suggested that the target compound produced by the reaction is quickly extracted and separated from the reaction phase to the extraction phase, thereby suppressing a subsequent side reaction.
[0010]
In the above-described example and the like, as shown in FIG. 2A, an organic phase (12) and a water phase (13) in which raw materials are dissolved are introduced into a Y-shaped microchannel (16), and a Y-shaped junction is formed. The reaction and extraction are performed at the fluid boundary (14) between the organic phase and the aqueous phase formed by the above. In general, in most cases, the Reynolds number is smaller than 1 in a micro-scale flow path, and unless the flow velocity is set to a very high value, a laminar flow state as shown in FIG. Further, since the diffusion time is proportional to the square of the width of the microchannel (9), the smaller the width of the microchannel, the more the mixing proceeds by the diffusion of molecules without the need to actively mix the reaction solution. Extraction is likely to occur. In general, the efficiency of the reaction or extraction is higher as the specific surface area is larger. Here, the specific boundary area means the ratio of the area of the interface to the total volume of the phase when the phase is in contact with each other to form the interface. In a reaction or extraction, since a substance can move to another phase only through an interface, a large specific surface area means that the efficiency of the reaction or extraction is higher.
[0011]
Hereinafter, a method for calculating the relative boundary area in the microchannel will be described with reference to FIG. FIG. 2B is a three-dimensional cross-sectional view in which a part of a part of the Y-shaped flow channel in FIG. 2A is cut out. If the width (9) of the microchannel is W [μm], the unit length (24) of the microchannel is L [μm], and the depth (25) of the microchannel is d [μm], the organic phase ( 12) is (W / 2) × d × L [μm ³ ]. The area of the fluid boundary (14) between the aqueous phase and the organic phase is d × L [μm ² ]. Accordingly, the specific area is (d × L) / {(W / 2) × d × L} = 2 × 10 ⁴ / W [cm ^-1 ], And it can be seen that the width is determined only by the width (W) of the microchannel regardless of the length and the depth (d) of the microchannel. For example, the specific boundary area where the width of the microchannel is 1000 [μm] is 20 [cm]. ^-1 In contrast, the specific boundary area where the width of the microchannel is 100 [μm] is 200 [cm ^-1 ]. Therefore, the smaller the width of the microchannel, the larger the specific surface area, and the higher the efficiency of the reaction and extraction.
[0012]
However, the efficiency of the reaction and extraction between laminar flows as shown in FIG. 2 (a) described above, conversely, shortens the diffusion time and the size of the specific boundary area of the fluid boundary, that is, the width of the microchannel. Means that it is limited by That is, the diffusion time and the relative boundary area of the fluid boundary are determined by the width of the microchannel used for the reaction and extraction, and the efficiency of the reaction and extraction can be improved to be more than the efficiency determined by the width of the microchannel. Can not. Also, as described above, if the width of the microchannel is reduced, the diffusion time can be further shortened to increase the specific area, and the efficiency of the reaction and extraction can be improved. Since the pressure loss is large and the liquid sending itself becomes difficult and impractical, there is a limit to reducing the width of the microchannel, and improvement has been required.
[0013]
[Non-patent document 1]
H. Hisamoto et. al. (H. Hisamoto et al.) "Fast and high conversion phase-transfer synthesis explosing the liquid-liquid interface formed in a microchannel chip.", Chem. Commun. , 2001, pp.2662-2663.
[Non-patent document 2]
Takashi Nishisako et al., "Creation of microdroplets in liquid in microchannel", Proceedings of the 4th Technical Meeting of the Society for Chemistry and Microsystems, p. 59, published in 2001
[Non-Patent Document 3]
Kikutani et al., “Synthesis in High-yield Microchannels Using a Pile-Up Microreactor,” Proceedings of the 3rd Chemistry and Microsystems Workshop, p. 9, 2001
[Patent Document 1]
Patent No. 2975943
[0014]
[Problems to be solved by the invention]
As described above, the first problem of the generation of microparticles in the microchannel according to the conventional technique is that when the microparticles generate uniform microparticles at the junction of the continuous phase and the dispersion phase, the dispersion phase and the continuous phase are This means that a laminar flow is formed, and it becomes impossible to stably generate fine particles at the junction.
[0015]
The second problem is that in order to generate fine particles at the junction, it is necessary to supply an excessive amount of the continuous phase. For example, the cost of the continuous phase in gel production is reduced, industrial mass production is performed, or the generation of fine particles itself is performed. Is difficult.
[0016]
A third problem is to enable the generation of composite capsules and multiple capsules.
[0017]
The fourth problem is that when the generated microparticles are microdroplets, the microdroplets are collected in a beaker or the like outside the microchannel, and when the microdroplets are cured by crosslinking polymerization or the like, the microdroplets are collected and then cured. By this time, the shape of the microparticles is lost, or the coalescence of the microparticles occurs, so that the variation in the particle size of the hardened microparticles increases. Also, it is difficult to separate the fine particles before curing from the medium.
[0018]
The fifth problem is that it is conventionally very difficult to uniformly distribute a fluid to a plurality of microchannels arranged two-dimensionally or three-dimensionally in a microchannel structure.
[0019]
A sixth problem is that the efficiency of reaction and extraction cannot be improved beyond the efficiency determined by the width of the microchannel.
[0020]
The object of the present invention has been made in view of the above problems, and enables generation of microparticles in a microchannel, generation of a composite capsule or multiple capsules, and uniform distribution of a fluid to a plurality of microchannels. By doing so, it is possible to respond to industrial mass production.Also, the microparticles are hardened immediately after the microparticles are generated without disturbing the shape of the microparticles generated using the microchannel, and the microparticles are separated from the medium. It is an object of the present invention to provide a method for producing microparticles and a microchannel structure therefor.
[0021]
Another object is to provide a method for producing a gel or a microcapsule.
[0022]
In addition, by using this microchannel structure, by shortening the diffusion time longer than determined by the width of the microchannel and obtaining the relative boundary area of the fluid boundary, the efficiency of extraction in the microchannel is improved. It is an object of the present invention to provide a solvent extraction method that improves the efficiency more than the efficiency determined by the width of the microchannel.
[0023]
[Means for Solving the Problems]
The microchannel structure of the present invention that solves the above problems includes an inlet and an introduction channel for introducing a dispersed phase, an inlet and an introduction channel for introducing a continuous phase, a dispersed phase and a continuous phase. A microchannel having a discharge channel for discharging microparticles generated by the method and a discharge port, and an introduction channel for introducing a dispersed phase. And an introduction channel for introducing a continuous phase intersect at an arbitrary angle, and the two introduction channels are connected to a discharge channel at an arbitrary angle. In addition, as a mode for producing a large amount of microparticles by parallelizing and / or laminating a large number of the microchannels, an inlet for introducing a fluid and an outlet for discharging the fluid are provided. A microchannel structure having a common channel communicating with the inlet and the outlet on the substrate, and one or more microchannels communicating with the common channel at a position different from the inlet and the outlet. Wherein the cross-sectional area of the common flow path gradually increases or is the same as the cross-sectional area from the position of communication with the inlet to the position of communication with the discharge port.
[0024]
In addition, the method for producing fine particles of the present invention is formed by an inlet and an introduction channel for introducing a dispersed phase, an inlet and an introduction channel for introducing a continuous phase, and a dispersed phase and a continuous phase. A method for generating microparticles using a microchannel structure having a discharge channel and a discharge port for discharging microparticles, wherein the dispersion is mainly performed at a junction where a dispersed phase and a continuous phase are merged. Production of microparticles that converts dispersed phase into microparticles by controlling the particle size of generated microparticles by changing the angle at which the introduction channel for introducing the phase and the introduction channel for introducing the continuous phase intersect Is the way. Further, by using the above-described microchannel structure, among microparticles, microcapsules and gels can be produced.
[0025]
Further, after the extraction solvent or the fluid containing the substance to be extracted is formed into microdroplets in the microchannel, the phase of the substance to be extracted is interposed between the dispersed phase composed of the microdroplets and the continuous phase surrounding the microdroplets. It can also be used as a solvent extraction method for performing solvent extraction by transfer.
[0026]
Hereinafter, the present invention will be described in more detail.
<Method for producing fine particles>
The microchannel used in the present invention generally indicates a channel having a width of 500 μm or less and a depth of 300 μm or less.
[0027]
The microparticles in the present invention are microparticles generated by a continuous phase shearing a dispersed phase in a microchannel, and the size of the microparticles is generally the diameter or width of the microchannel. Smaller than that. For example, the size of a microparticle generated in a microchannel having a width of 100 μm and a depth of 50 μm is smaller than 50 μm assuming that the microparticle is a perfect sphere. The microparticles in the present invention include not only solid microparticles but also microdroplets, semi-cured microparticles in which only the surface of the microdroplets are hardened, and semi-solid microparticles having extremely high viscosity. .
[0028]
Further, the dispersed phase used in the present invention is a liquid material for generating microparticles by the microchannel structure, for example, a monomer for polymerization such as styrene, a crosslinking agent such as divinylbenzene, a polymerization initiator Etc. refers to a medium in which a raw material for producing a gel is dissolved in a suitable solvent. Here, as the dispersed phase, the purpose of the present invention is to efficiently generate fine microparticles, and in order to achieve this purpose, a liquid that can be sent through a channel in a microchannel structure is used. There is no particular limitation as long as the fine particles can be formed. Further, the slurry may be a slurry in which solids such as fine powders are mixed in the dispersed phase, or may be a laminar flow in which the dispersed phase is formed from a plurality of fluids. Or a suspension (emulsion) formed from the above fluid.
[0029]
The continuous phase used in the present invention is a liquid substance used to generate fine particles from the dispersed phase by the fine channel structure, and for example, a dispersant for gel production such as polyvinyl alcohol in a suitable solvent. Refers to the medium dissolved in Here, similarly to the dispersed phase, the continuous phase is not particularly limited as long as it can feed a flow path in the fine flow path structure, and the component thereof is not particularly limited as long as fine particles can be formed. Further, the slurry may be a slurry in which solid substances such as fine powders are mixed in the continuous phase, or may be a laminar flow in which the dispersed phase is formed from a plurality of fluids. Or a suspension (emulsion) formed from the above fluid. From the viewpoint of the generated microparticle composition, the outermost layer of the continuous phase is an aqueous phase if the outermost layer of the microparticles is an organic phase, and the outermost layer of the continuous phase if the outermost layer of the microparticles is an aqueous phase. Becomes an organic phase.
[0030]
Further, it is preferable that the dispersed phase and the continuous phase do not substantially mix with each other or have no compatibility in order to generate fine particles.For example, when an aqueous phase is used as the dispersed phase, water is preferably used as the continuous phase. An organic phase such as butyl acetate, which is substantially insoluble in water, will be used. When an aqueous phase is used as the continuous phase, the reverse is true.
[0031]
In the method for producing microparticles of the present invention, the dispersed phase and the continuous phase described above are introduced into the microchannel structure according to the present invention from the introduction channel described below, and the dispersed phase is formed as a continuous phase at a junction where both are joined. It is to generate fine particles by shearing, but by changing the angle at which the introduction flow path for introducing the dispersed phase and the introduction flow path for introducing the continuous phase, the particle size of the generated fine particles Can be controlled. This is easier to control in the generation of microparticles using the conventional microchannel structure than changing the introduction speed of the dispersed phase and the continuous phase, and is suitable for industrial mass production. In particular, when the introduction speed of the dispersed phase and the introduction speed of the continuous phase are substantially the same, it is sufficient in terms of cost, such as preparing one introduction device. In addition, the phrase that the introduction speed of the dispersed phase and the introduction speed of the continuous phase are substantially the same means that the fluctuation of the introduction speed does not significantly affect the particle size of the generated fine particles. Means. By doing so, it is possible to generate microparticles having a stable particle size, and it is not necessary to supply an excessive amount of the continuous phase, and for example, it is possible to reduce the cost of the continuous phase in gel production and to achieve industrial mass production. Become.
[0032]
As a method of merging the continuous phase and the dispersed phase in the present invention, basically, the continuous phase is introduced from the continuous phase inlet (2) of the Y-shaped microchannel as shown in FIG. The dispersed phase is introduced from the inlet (4), and the dispersed phase is sheared by the continuous phase at the junction (6) to generate the fine particles (17). However, the present invention is not limited to this method. As shown in FIG. 4, the dispersed phase (15) is brought into contact with the continuous phase (10) so as to sandwich the continuous phase (10), and the dispersed phases are merged. A method of generating microparticles (17) by shearing in the portion (6) may be used, or as shown in FIG. 5, two or more dispersed phases () may be sandwiched by the microchannel (16) so as to sandwich the continuous phase (10). 15) may be in contact with each other and the dispersed phase may be a continuous phase and shear at the junction (6) to generate fine particles (17). Alternatively, as shown in FIG. ), The dispersed phase (15) is introduced from one side, and the continuous phase (16) is introduced from the other side, and the dispersed particles and the continuous phase are merged at the junction (6) to form the fine particles (17). Generated and discharged in one or more arbitrary directions from the merged position It may be. By doing so, fine particles can be generated more efficiently. In the case of the method shown in FIG. 6, the generated fine particles can be collected by rejoining the fluid containing the generated fine particles.
[0033]
Also, as shown in FIGS. 7A to 7G, a dispersed phase introduction channel (5) for introducing one or a plurality of dispersed phases (15) and a continuous phase for introducing one or a plurality of continuous phases (10). By providing the phase introduction channel (3), the disperse phase or the continuous phase can be a laminar flow of a plurality of fluids or a mixed solution or suspension (emulsion). By doing so, fine particles having a multilayer structure or fine particles containing various kinds of fine particles can be formed, and composite microcapsules and multiple microcapsules can be generated. The continuous phase, the dispersed phase, or both of them may contain fine powder.
[0034]
In the present invention, when the microparticles generated at the junction of the microchannels are microdroplets and the microdroplets are cured, the microparticles may be cured inside and / or outside the microchannels. Further, in order to make the particle size of the hardened fine particles uniform, after the fine liquid droplets pass through the discharge flow path and exit from the discharge part, the discharge part of the fine flow path structure externally connects to the outside of the fine flow path structure. May be continuously hardened by the fine flow channel provided in the substrate. Furthermore, in order to make the particle size of the cured microparticles more uniform, immediately after microdroplets are generated at the confluence of the microchannels, the microparticles in the microchannel structure, ie, the discharge channels, are hardened. More preferably.
[0035]
One of the means for hardening the microdroplets in the present invention is to harden the microdroplets by irradiating the microdroplets with light. It is preferable to use ultraviolet light because it can be selected from the following. The light irradiation (21) may be performed after the microdroplets have come out of the microchannel structure from the outlet (8) of the microchannel structure (19) as shown in FIG. 8A. However, in order to make the particle size of the microparticles more uniform, as shown in FIG. 8B, light irradiation (21) is performed immediately after microdroplets are generated at the junction (6) of the microchannels. More preferably, the curing is performed in the discharge channel (7) in the microchannel structure (19). However, when light irradiation is performed in the discharge channel in the microchannel structure, before the microdroplets are generated, the dispersed phase is irradiated with light before the microdroplets are generated so as not to be cured. As shown in FIG. 8B, the portion of the discharge channel and the portion of the discharge channel that cures the microdroplets by irradiating light are provided only at the necessary portions of the microchannel structure, as shown in FIG. ) Must be installed so that the mask (22) can be hit.
[0036]
Another means for curing the microdroplets in the present invention is a method for producing microparticles using means for curing the microdroplets by heating. As shown in FIG. 9A, even when heating is performed by a heater (28) or the like after the minute liquid droplets exit the outside of the minute channel structure from the outlet (8) of the minute channel structure (19). However, in order to make the particle size of the microparticles more uniform, as shown in FIG. 9B, heating is performed by a heater or the like immediately after microdroplets are generated at the junction (6) of the microchannels. More preferably, the curing is performed in the discharge channel (7) in the microchannel structure. However, when heating is performed in the discharge channel in the microchannel structure, the discharge flow before the microdroplet is generated so that the disperse phase is not heated and hardened before the microdroplet is generated. It is necessary to thermally insulate the part of the passage and the part of the discharge flow path that heats and hardens the microdroplets by a known heat insulation method such as embedding a heat insulator or the like in the microchannel structure. is there.
[0037]
When the microdroplets are cured by light irradiation or heating in the present invention, the entirety of the microdroplets may be cured. Curing may be performed to such an extent that coalescence does not occur. In this case, the semi-cured fine particles are collected in a beaker or the like, and are completely cured again by light irradiation or heating, whereby fine particles having a uniform particle diameter can be obtained.
In this way, if the microparticles generated at the confluence of the microchannels are microdroplets, they are collected in a beaker or the like outside the microchannels and hardened by crosslinking polymerization. From the collection to the hardening, the shape of the fine particles collapses and coalescence of the fine particles occurs, so that the variation in the particle size of the hardened fine particles does not increase, and the particle size is uniform. Fine particles can be obtained. Further, the hardening of the microdroplets facilitates separation from the medium.
[0038]
As described above, as one of the most preferable embodiments of the method for producing microparticles of the present invention, the dispersed phase is a medium containing a raw material for gel production, and an inlet and an introduction channel for introducing the dispersed phase, The continuous phase is a medium containing a dispersant for gel production, and an inlet and an introduction channel for introducing the continuous phase, and a discharge channel and a drain for discharging fine particles generated by the dispersed phase and the continuous phase. A method for generating microparticles using a microchannel structure having an outlet, wherein the disperse phase and the continuous phase are merged to form the disperse phase into microparticles, and an introduction flow for introducing the disperse phase is provided. The particle diameter of the generated fine particles is controlled by changing the angle at which the flow path intersects with the introduction flow path for introducing the continuous phase, and the fine particles are illuminated in the fine flow path and / or outside the fine flow path. This is a method of curing by irradiation and / or heating.
[0039]
In the method for producing fine particles of the present invention, examples of uses of the fine particles include a filler for a column for high performance liquid chromatography, an adhesive such as a seal lock agent, insulating particles of metal particles, a pressure measurement film, and a carbonless (pressure-sensitive). Copy) paper, toner, thermal expansion agent, heat medium, light control glass, gap agent (spacer), thermochromic (thermosensitive liquid crystal, thermosensitive dye), magnetophoretic capsule, pesticide, artificial feed, artificial seed, fragrance, Microcapsules and gels such as massage creams, lipsticks, vitamin capsules, activated carbon, enzyme-containing capsules, and DDS (drug delivery system) are mentioned.
<Microchannel structure>
The microchannel structure of the present invention includes an inlet and an inlet channel for introducing a dispersed phase, an inlet and an inlet channel for introducing a continuous phase, and a microparticle formed by the dispersed phase and the continuous phase. A microchannel structure comprising a microchannel having a discharge channel and a discharge port for discharging particles, wherein an introduction channel for introducing a dispersed phase and a continuous phase are introduced. And the two introduction channels are connected to the discharge channel at an arbitrary angle, and the form of the micro channel structure is characterized in that: Is a microchannel structure as shown in FIGS. It should be noted that the microchannel structure of the present invention is not limited to the examples shown in FIGS. 3 to 7 and can be arbitrarily changed without departing from the gist of the present invention. Further, the aspect ratio (ratio of depth / width of the flow channel) of the flow channel cross section of the micro flow channel structure of the present invention is 0.30 or more and less than 3.0. is there.
[0040]
Here, the inlet for introducing the disperse phase means an opening for introducing the disperse phase, and a mechanism for continuously introducing the disperse phase may be provided by providing an appropriate attachment to the inlet. Similarly, the introduction port for introducing the continuous phase also means an opening for introducing the continuous phase, and a mechanism for continuously introducing the continuous phase by providing an appropriate attachment to this introduction port. Good.
[0041]
The introduction flow path for introducing the dispersed phase communicates with the introduction port, and the dispersed phase is introduced and sent along the introduction flow path. The shape of the introduction channel has an effect on controlling the shape and particle size of the fine particles, but the width may be about 300 μm or less, and the shape may be such that it merges at an arbitrary angle including the discharge channel. Similarly, the introduction flow path for introducing the continuous phase is also in communication with the introduction port, the continuous phase is introduced, and the liquid is sent along the introduction flow path. The shape of the introduction channel has an effect on controlling the shape and particle size of the fine particles, but the width may be about 300 μm or less, and the shape may be such that it merges at an arbitrary angle including the discharge channel.
[0042]
The discharge flow path communicates with the two introduction flow paths and the discharge port, and after the dispersed phase and the continuous phase merge, the liquid is sent along the discharge flow path and discharged from the discharge port. Although the shape of the discharge channel is not particularly limited, it is sufficient that the width of the discharge channel is about 300 μm or less and that it merges at an arbitrary angle including the introduction channel. Further, the discharge flow path may be two or more discharge flow paths separated from the junction at an arbitrary angle. The outlet means an opening for discharging the generated microparticles, and furthermore, the outlet may be provided with an appropriate attachment to provide a mechanism for continuously discharging the phase containing the generated microparticles. . Note that these channels may be referred to as minute channels in this specification.
[0043]
Furthermore, in the microchannel structure of the present invention, the introduction channel for introducing the dispersed phase and the introduction channel for introducing the continuous phase intersect at an arbitrary angle, and these introduction channels are optional. It is preferable that the structure is such that it is connected to the discharge channel at an angle of. By setting the angle at which the two introduction flow paths intersect to an arbitrary angle, it is possible to control the fine particles generated at the junction to a desired particle size. The setting of the intersection angle may be appropriately determined according to the target particle size of the fine particles.
[0044]
As the cross-sectional shape of the introduction flow path and the discharge flow path, it is preferable that the aspect ratio of the flow path cross section is 0.30 or more and less than 3.0. If the aspect ratio is within this range, uniform fine particles can be generated at the junction. If the aspect ratio is out of this range and is less than 0.30 or 3.0 or more, it may be difficult to generate uniform fine particles.
[0045]
Furthermore, when the width and depth of the introduction flow path for introducing the dispersed phase and the introduction flow path for introducing the continuous phase are equal, in addition to the above effects, the design of the micro flow path structure becomes easy, In addition, the control during liquid feeding becomes easier, which is suitable for industrial mass production.
[0046]
In addition, in the relationship between the width of the introduction flow path and the width of the discharge flow path, if the width of the introduction flow path ≥ the width of the discharge flow path, the width of the introduction flow path <the width of the discharge flow path, Even if is increased, uniform fine particles can be generated at the junction, and the effect of increasing the generation speed of the fine particles can be obtained, which is a preferable embodiment.
[0047]
As the width of the discharge channel, it is preferable that the width of the discharge channel is narrow at a part of the discharge channel from the intersection of the dispersed phase and the continuous phase to the discharge port. In other words, a part of the flow path forming wall along the dispersed phase flow path is formed to be narrower at the confluence of the introduction flow path and the discharge flow path, or to a convex shape, before reaching the discharge port of the fine particles. Alternatively, as shown in FIGS. 32 (a) to 32 (e), one or more projections are formed from any one or two or more of the bottom, top, and side surfaces of the flow path to increase the liquid sending speed. This also makes it possible to generate uniform fine particles at the confluence portion and to alleviate a rise in liquid sending pressure, which is a preferable embodiment.
[0048]
Further, it is preferable that the portion where the width of the discharge flow path is narrow is located at or near the intersection in the discharge flow path. In particular, the portion where the width of the discharge flow path is narrow is the discharge flow path At the intersection of the disperse phase and the introduction flow path.
[0049]
In addition, the microchannel structure of the present invention can industrially generate a large amount of microparticles by arranging a plurality of microchannels in the microchannel structure in a planar or three-dimensional manner. However, it is necessary to uniformly distribute the fluid to a plurality of microchannels arranged two-dimensionally or three-dimensionally. For this reason, the microchannel structure of the present invention includes an inlet for introducing a fluid and an outlet for discharging the fluid, and a common channel communicating with the inlet and the outlet on the substrate, A microchannel structure having a microchannel that communicates with a common channel at a position different from the inlet and the outlet, wherein the cross-sectional area of the common channel is closer to the outlet than the communication position with the inlet. It is preferred that the size gradually increases or becomes the same toward the communication position.
[0050]
FIG. 10 shows the most basic conceptual diagram of the microchannel structure. A common flow path inlet (32) for introducing a fluid and a common flow path discharge port (31) for discharging a fluid are provided at both ends of the common flow path (29). A microchannel (16) having an inner diameter (channel width) smaller than the common channel was disposed on the substrate between the discharge ports. Generally, the inside diameter of the microchannel is about several tens to 300 μm. On the other hand, the inner diameter of the common flow path is desirably about 500 μm to several mm. The inner diameter of the flow path connecting the common flow path inlet and the common flow path is not particularly limited, but is preferably about 500 μm to several mm similarly to the common flow path. The inner diameter of the flow path connecting the common flow path outlet and the common flow path is not particularly limited, but is preferably about several tens to 300 μm as in the case of the fine flow path.
[0051]
In addition, there is no particular limitation on the arrangement of the microchannels as long as they communicate with the common channel at a position different from the common channel inlet and the common channel outlet. To illustrate this point more specifically, as shown in FIG. 10, the microchannel Y closest to the common channel inlet is provided. ₁ From the micro channel Y closest to the common channel outlet _n In the common flow channel of the micro flow channel structure where n micro flow channels communicate with the common flow channel, the position of communication with the common flow channel inlet is X ₀ , The microchannel Y closest to the common channel inlet ₁ The communication position of X ₁ , Communication position X ₀ And communication position X ₁ A along the common flow path between ₁ , The communication position with the common channel outlet is X _{n + 1} , The microchannel Y closest to the common channel outlet _n The communication position of X _n , Communication position X _n And communication position X _{n + 1} A along the common flow path between _{n + 1} And Y ₁ To Y _n Fluid can be uniformly distributed in the microchannels up to and the generation of microdroplets can be performed efficiently. ₂ From a _n Are preferably set to be equal to each other. Furthermore, a ₁ ~ A _{n + 1} This effect can be further improved by making all of them equal.
[0052]
Further, in such a minute channel structure, a structure in which a plurality of common channels are provided on the substrate and each common channel is communicated with the minute channel may be employed.
[0053]
11 to 14 show conceptual diagrams of some embodiments of the present invention. It is needless to say that the present invention is not limited to only these forms, and can be arbitrarily changed without departing from the gist of the invention.
[0054]
FIG. 11 shows an example in which the inner diameter of the common channel (19) gradually increases from the common channel inlet (32) toward the common channel outlet (31). In this case, the inner diameter (shown by b) of the common flow path near the common flow inlet is about 500 μm to 1 mm, and the inner diameter (shown by c) of the common flow path near the common flow outlet is several mm. It is about.
[0055]
FIG. 12 shows that two common flow paths (29) ₁ To Y _n This is an example in which the minute flow path (16) indicated by "" is drawn out and merged in a Y-shape. By introducing the continuous phase and the dispersed phase used in the method for producing microparticles of the present invention into two common channels using the microchannel structure shown in FIG. 12, a plurality of Y-shaped microchannels are introduced. The continuous phase and the dispersed phase can be evenly distributed in the channels, and under the same conditions in all of the microchannels, extremely fine particle systems can be generated. This mode is effective when a large number of microchannels are planarly integrated when the microchannel substrate is a square substrate.
[0056]
FIG. 13 shows an example in which the common flow paths (29) are arranged in an arc shape. In this case, the microchannels (16) were arranged radially at an equal angle d from the center of the arc. This mode is effective when a large number of minute channels are planarly integrated when the minute channel substrate is a disk-shaped substrate. In this case, as in FIG. 10, the communication position with the common flow channel introduction port (32) is set to X. ₀ , The microchannel Y closest to the common channel inlet ₁ The communication position of X ₁ , Communication position X ₀ And communication position X ₁ A along the common flow path between ₁ And so on, a ₁ ~ A _{n + 1} Means the length along the center of the arc-shaped common flow path.
[0057]
FIG. 14 shows an example in which a microchannel substrate (1) having a microchannel (16) is overlapped, and a common channel (29) is configured to penetrate the microchannel substrate. This mode is effective when the microchannel substrates are stacked and a large number of microchannels are three-dimensionally integrated. The size of the inner diameter of the through-hole may gradually increase from the fluid common flow channel inlet (32) to the fluid common flow channel outlet (31) as in FIG.
[0058]
Further, in the various embodiments of the present invention shown in FIGS. 10 to 14, the fluid is generally introduced into the common flow channel introduction port (32) using a liquid feed pump such as a syringe pump, but is arranged in the common flow channel. The fluid discharged from the common channel discharge port (31) that has been collected can be collected and returned to the liquid supply pump again to transmit the liquid again. That is, each of the plurality of common channels is communicated with the minute flow channel, The structure may be such that the fluid discharged from the passage discharge port is returned to the respective common flow path introduction ports. In this way, the continuous phase and / or the dispersed phase to be introduced can be used without waste. Further, it is preferable to introduce and discharge the dispersed phase into at least one of the common flow paths and the continuous phase into at least one other common flow path.
[0059]
Although the microchannel structure of the present invention has the structure and performance described above, the introduction section and the introduction flow path for introducing the dispersed phase and the continuous phase, and the junction where the introduction flow path intersects A microchannel structure having a discharge channel and a discharge port for discharging a liquid covers a substrate having a microchannel formed on at least one surface and a substrate surface having a microchannel formed thereon. In addition, a cover body in which a small hole for communicating the microchannel and the outside of the microchannel structure may be laminated and integrated at a predetermined position of the microchannel. As a result, fluid can be introduced from the outside of the microchannel structure to the microchannel, and can be discharged again to the outside of the microchannel structure. It is possible to pass through the minute channel. Fluid delivery is enabled by mechanical means such as a micropump.
[0060]
As a material of the substrate and the cover body in which the minute flow path is formed, a material which can form the minute flow path, has excellent chemical resistance, and has appropriate rigidity is preferable. For example, it may be glass, quartz, ceramic, silicon, metal or resin. The size and shape of the substrate and the cover are not particularly limited, but the thickness is desirably about several mm or less. When the small hole arranged in the cover communicates the microchannel with the outside of the microchannel structure and is used as a fluid inlet or outlet, its diameter is desirably, for example, several mm or less. The small holes in the cover body can be processed chemically, mechanically, or by various means such as laser irradiation or ion etching.
[0061]
Further, in the microchannel structure of the present invention, the substrate on which the microchannel is formed and the cover are laminated and integrated by means such as heat bonding or bonding using an adhesive such as a photo-curing resin or a thermosetting resin. be able to.
<Solvent extraction method using microchannel structure>
By using the microchannel structure of the present invention, after the extraction solvent or the fluid containing the substance to be extracted is converted into microdroplets in the microchannel, a dispersed phase composed of the microdroplets and a continuous phase surrounding the microdroplets are formed. There is a use as a solvent extraction method in which a solvent is extracted by transferring a substance to be extracted between phases.
[0062]
In the solvent extraction method of the present invention, one of the extraction solvent and the fluid containing the substance to be extracted can be arbitrarily selected as the dispersed phase and the other as the continuous phase. Here, the substance to be extracted indicates a substance to be extracted, and the fluid containing the substance to be extracted means a liquid in which the substance to be extracted is dissolved. The extraction solvent means a liquid for extracting the substance to be extracted from the fluid containing the substance to be extracted, and is desired to be capable of dissolving the substance to be extracted and having a higher solubility for the substance to be extracted than the fluid containing the substance to be extracted. Solvent extraction means that the substance to be extracted is transferred from the fluid containing the substance to be extracted to the extraction solvent by phase transfer, and the phase transfer is the transfer from the phase of the fluid containing the substance to be extracted to the phase of the extraction solvent. Means
[0063]
In the present invention, one of the extraction solvent and the fluid containing the substance to be extracted can be arbitrarily selected as the dispersed phase and the other as the continuous phase. The size of the microdroplet is generally smaller in diameter than the width or depth of the microchannel. For example, the size of a droplet generated in a microchannel having a width of 100 μm and a depth of 50 μm is smaller than 50 μm assuming that the droplet is a perfect sphere.
[0064]
This solvent extraction method determines the extraction efficiency in the microchannel by the width of the microchannel by shortening the diffusion time longer than determined by the width of the microchannel and obtaining the size of the relative boundary area of the fluid boundary. The improvement of the efficiency beyond the required efficiency will be described with reference to FIG.
[0065]
As shown in FIG. 15, when the diameter (33) of the spherical microdroplet is D [μm], the total volume of the microdroplet is (4π / 3) × (D / 2) ³ [Μm ³ ]. The surface area of the microdroplet is 4π × (D / 2) ² [Μm ² ]. Therefore, the relative boundary area between the microdroplet (34) and the surrounding medium is ｛4π × (D / 2) ² ｝ / ｛(4π / 3) × (D / 2) ³ ｝ = 6 × 10 ⁴ / D [cm ^-1 ]. On the other hand, as shown in FIG. 1, the relative boundary area of the fluid boundary (14) formed in the microchannel (16) is 2 × 10 ⁴ / W [cm ^-1 ]. Generally, since the diameter D of the microdroplet formed by the microchannel is smaller than the width (9) W of the microchannel, D <W. The specific boundary area is simply larger than the specific boundary area of the fluid boundary formed by the microchannel, and the diffusion time between the microdroplets and the surrounding solvent is simply caused by the laminar flow in the microchannel. It is shorter than the diffusion time. Therefore, if microdroplets of a fluid containing an extraction solvent or a substance to be extracted are formed in a microchannel, the diffusion time shorter than determined by the width of the microchannel and the size of the relative boundary area of the fluid boundary can be reduced. As a result, the extraction efficiency in the microchannel can be improved to be higher than the efficiency determined by the width of the microchannel.
[0066]
The target to be converted into microdroplets may be an extraction solvent or a fluid containing the substance to be extracted, but by selectively forming either of them into microdroplets, the extraction phase can be further separated after extraction. It is possible to select an object to be formed into fine droplets according to an easy mode. In the method for producing microparticles of the present invention, the liquid droplets are formed into droplets by appropriately controlling the flow rates of the respective fluids to be combined or by changing the hydrophilicity and hydrophobicity of the inner wall of the microchannel by a method known per se. It is possible to select whether the object is an extraction solvent or a fluid containing the substance to be extracted, and it is possible to select an object to be formed into microdroplets according to a mode in which the extraction phase is more easily separated after the extraction. In addition, the diameter of the microdroplets can be controlled by the flow velocity, the angle at which the microchannels meet at the junction, the width and the depth of the microchannels, or a combination of these, so that the specific boundary area can be increased. Can be controlled accurately.
[0067]
In the solvent extraction method of the present invention, the substance to be extracted is a product obtained by chemically reacting two or more kinds of fluids, and the fluid containing the substance to be extracted separately separates two or more kinds of fluids containing raw materials into fine particles. It may be a fluid obtained by being introduced into and brought into contact with a flow channel. By doing so, the product obtained by the reaction in the microchannel can be promptly extracted with the solvent immediately after the production, and it is possible to suppress side reactions and control the equilibrium reaction. .
[0068]
FIG. 16 shows that the fluid containing the substance to be extracted introduces fluid A (35) and fluid B (36) having raw materials separately into the microchannel (16) and mixes them in the reaction phase (37) in the microchannel. FIG. 5 is a diagram showing a concept in the case of a fluid that has been reacted. In the example of FIG. 16, the fluid containing the substance to be extracted was the continuous phase (10), and the extraction solvent (38) was the dispersed phase (15).
[0069]
In the solvent extraction method of the present invention, the extraction target material obtained by separately introducing two or more kinds of fluids containing the raw material and the extraction solvent into the microchannel and bringing the two or more kinds of fluids containing the raw material into contact with each other is used. In the method of extracting into an extraction solvent phase, two or more fluids containing a raw material form a laminar flow, and a substance to be extracted is generated at a boundary between the fluids, and the extraction solvent is two or more fluids containing the raw material. A liquid droplet may be formed on the fluid boundary by being sheared at the junction, and the generated substance to be extracted may be extracted into liquid droplets of the extraction solvent. By doing so, a solvent other than the solvent used in the reaction system can be introduced as the extraction solvent, and for example, a solvent having a higher product extraction efficiency can be used as the extraction solvent. In addition, since a product generated by a reaction generated at a fluid boundary can be promptly extracted with a solvent immediately after the generation, a side reaction can be suppressed and an equilibrium reaction can be controlled.
[0070]
FIG. 17 shows a fluid A (35) and a fluid B (36) having raw materials as continuous phases (10) in a microchannel (16) for obtaining a product by a reaction occurring at a fluid boundary (14). FIG. 3 is a diagram illustrating a concept of extracting a product generated at a fluid boundary by forming a microdroplet (34) at a fluid boundary by shearing an extraction solvent (38) at a fluid boundary in a continuous phase.
[0071]
Further, the solvent extraction method as a use of the microparticles of the present invention, after performing the solvent extraction in the microchannel, by hardening at least the surface of the microdroplets, even if the continuous phase and the dispersed phase can be separated good. In this way, the dispersed phase of the microdroplets and the continuous phase surrounding the microdroplets can be more easily separated, and the extraction solvent and the fluid containing the substance to be extracted can be easily separated. Can be.
[0072]
For example, as shown in FIG. 18, a fluid containing a substance to be extracted is formed into a fine droplet by dispersing the fluid into a dispersed phase (15), and the substance to be extracted is extracted into a continuous phase (10) by an interphase transfer. 39), the microparticles (17) are formed by curing at least the surface of the microdroplets (34) by irradiation with ultraviolet light (21), so that the liquid phase of the continuous phase and the solid phase of the microparticles are formed. Can be easily separated using a method such as filtration, and the substance to be extracted can be easily recovered. In the example of FIG. 18, the liquid containing the substance to be extracted as the disperse phase is selected from a liquid that is cured by ultraviolet irradiation.
[0073]
Conversely, as shown in FIG. 19, the extraction-substance-containing fluid is converted into a continuous phase (10), and the extraction solvent (38) is converted into microdroplets to form a dispersed phase (15). After the extraction (39), if at least the surface of the microdroplets (34) is cured by irradiation with ultraviolet rays to form the microparticles (17), the liquid phase of the continuous phase and the solid phase of the microparticles are similarly formed. It can be easily separated using a technique such as filtration. In this case, the surface having the substance to be extracted is hardened, and the surface of the fine particles may be divided by any method, chemical or mechanical, to extract the substance to be extracted present inside the fine particles. In the example of FIG. 19, as the extraction solvent as the disperse phase, a liquid that is cured by irradiation with ultraviolet rays can be selected.
[0074]
In the examples of FIGS. 18 and 19 described above, the means for curing the surface of the microdroplets is irradiated with ultraviolet rays. However, in addition to the irradiation of ultraviolet rays, crosslinking and polymerization are performed by heating or a chemical reaction as shown in FIG. For example, it may be selected according to the material of the dispersed phase to be cured.
[0075]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, examples of the present invention will be described, and embodiments of the present invention will be described in more detail. It is needless to say that the present invention is not limited to the following embodiments, and can be arbitrarily changed without departing from the gist of the present invention.
[0076]
(Example 1)
FIG. 20 shows a microchannel in the first embodiment of the present invention. The microchannels are formed on a 70 mm × 20 mm × 1 t (thickness) Pyrex (registered trademark) glass, and a continuous phase introduction channel (2), a dispersed phase introduction channel (4), and a discharge channel corresponding to the microchannels. Each of (7) has a width of 220 μm, a depth of 80 μm, an aspect ratio of a microchannel = 0.36, a length of a discharge channel of 30 mm, a continuous phase introduction channel (3) and a dispersed phase introduction channel ( 5), one Y-shaped flow path having a merging portion intersecting at an angle of 44 ° was formed. The width and depth of the microchannel depend on the particle size of the generated microparticles, but it is sufficient that the aspect ratio of the microchannel does not deviate from the range of 0.30 or more and less than 3.0.
As shown in FIG. 21, the microchannel structure having the microchannels has a microchannel formed on one surface of a glass substrate having a thickness of 1 mm and a size of 70 mm × 20 mm by general photolithography and wet etching. Then, a small hole having a diameter of 0.6 mm was previously formed on the surface of the glass substrate having the microchannels having the microchannels at positions corresponding to the introduction port (11) and the discharge port (8) of the microchannels by a mechanical method. A glass cover body (30) having a thickness of 1 mm and a size of 70 mm × 20 mm, which was provided by using processing means, was manufactured by thermal bonding. The manufacturing method and the substrate material are not limited to these.
[0077]
Next, the method for producing fine particles of the present invention will be described. As shown in FIG. 22, a liquid is supplied to the microchannel structure (19) by a holder (23) or the like so that the liquid can be sent to the microchannel structure (19), and a Teflon (registered trademark) tube (27) and a fillet joint (40) are held by the holder. Fixed to. The other end of the Teflon tube is connected to a microsyringe (42). This enables liquid to be sent to the microchannel structure. Next, a mixed solution of divinylbenzene and butyl acetate is injected into a dispersed phase for generating fine particles, and a 3% aqueous solution of polyvinyl alcohol is injected into each microsyringe into a continuous phase, and the liquid is sent by a microsyringe pump (41). Was. The liquid sending speed is 20 μl / min for both the dispersed phase and the continuous phase. In a state where the liquid sending speeds were both stable, generation of fine particles as shown in FIG. 23 was observed at the junction where the dispersed phase and the continuous phase of the fine channel structure intersect. Observation of the generated fine particles revealed that the average particle size was 200 μm and the CV value (%) indicating the degree of dispersion of the particle size was 9.8%, as shown in FIG. When the liquid sending speed was 1 μl / min for both the dispersed phase and the continuous phase, the average particle size of the generated fine particles was 230 μm, and the CV value (%) indicating the degree of dispersion of the particle size was 9.5%. , And were extremely uniform fine particles. Thus, the dispersed phase and the continuous phase are performed at the same liquid sending speed, so that uniform fine particles can be generated without excessively sending the continuous phase.
[0078]
(Example 2)
FIG. 25 shows a microchannel in the second embodiment of the present invention. The micro channels are formed on a 70 mm × 40 mm × 1 t (thickness) Pyrex (registered trademark) glass, a continuous phase introduction channel (3), a dispersed phase introduction channel (5), and a discharge channel corresponding to the micro channels. Each of (7) has a width of 185 m, a depth of 75 μm, an aspect ratio of the microchannel = 0.41, a length of the discharge channel (7) of 30 mm, and a continuous phase introduction channel and a dispersed phase introduction channel. Formed two Y-shaped flow paths having a junction where they intersect at angles of 22 ° and 44 °. The width and depth of the microchannel depend on the particle size of the generated microparticles, but it is sufficient that the aspect ratio of the microchannel does not deviate from the range of 0.30 or more and less than 3.0. The microchannel structure having the microchannel was manufactured in the same manner as in Example 1.
[0079]
Next, the microchannel structure is held by a holder, and a mixed solution of a monomer (styrene), divinylbenzene, butyl acetate, and benzoyl peroxide is added to the dispersed phase for generating microparticles in the same manner as in Example 1. Then, a 3% aqueous solution of polyvinyl alcohol was poured into the microsyringe into the continuous phase, and the solution was fed by a microsyringe pump. The crossing angle between the continuous phase introduction channel and the dispersed phase introduction channel was 44 ° and 22 °. went. The liquid sending speed is 20 μl / min for both the dispersed phase and the continuous phase. With both the flow rates stable, generation of fine particles was observed at the junction where the dispersed phase and the continuous phase of the microchannel structure intersect. Observing the generated microparticles, when the merging portions intersect at an angle of 22 °, the average particle size is 180 μm, the CV value (%) indicating the degree of dispersion of the particle size is 8.7%, and when the confluence is 44 °, the average is 44%. The particle size was 160 μm, and the CV value (%) indicating the degree of dispersion of the particle size was 9.2%. In addition, when the microparticles generated when the dispersion phase and the continuous phase were both performed at 5 μl / min were observed, the average particle diameter was 250 μm and the degree of dispersion of the particle diameter was determined when the confluence part intersected at 22 °. The CV value (%) indicated was 9.4%, the average particle diameter was 220 μm at 44 °, the CV value (%) indicating the degree of dispersion of the particle diameter was 8.5%, and the angle of the junction was 22%. When the angle of the confluence is 44 °, the particle diameter becomes 0.89 times that in the case of °. Thus, the width and depth of the introduction channel are constant, and the particle size can be reduced by changing only the angle of the junction of the introduction channel without changing the conditions of the liquid feeding speed of the dispersed phase and the continuous phase to be introduced. Control becomes possible.
[0080]
(Comparative Example 1)
FIG. 26 shows a microchannel in Comparative Example 1. The micro flow path is formed on a Pyrex (registered trademark) glass of 70 mm × 20 mm × 1 t (thickness), and the width of the continuous phase introduction flow path (3), the dispersed phase introduction flow path (5), and the discharge flow path (7) is set. Each of them is 130 μm, depth 35 μm, the aspect ratio of the microchannel is 0.27, the length of the discharge channel is 30 mm, and the continuous phase introduction channel and the dispersed phase introduction channel intersect at an angle of 44 °. One Y-shaped channel having a portion was formed. This microchannel structure was manufactured in the same manner as in Example 1.
[0081]
Next, the microchannel structure was held by a holder, and a mixed solution of divinylbenzene and butyl acetate was used as a dispersed phase for generating microparticles in the same manner as in Example 1, and a 3% aqueous solution of polyvinyl alcohol was used as a continuous phase. The solution was injected into a microsyringe and fed. The liquid sending speed is 5 μl / min for both the dispersed phase and the continuous phase. Observation of the junction where the dispersed phase and the continuous phase of the microchannel structure intersect in a state where the flow rates are both stable shows that microparticles can be generated, but separation and coalescence occur in the discharge channel, and the particles are generated. Observation of the microparticles showed that the CV value (%) indicating the degree of dispersion of the particle diameter was 36.5%, indicating that the microparticles had poor dispersibility. In the case where fine particles having good dispersibility are generated by the fine channel structure having this aspect ratio, the liquid sending speed is set to a continuous phase> disperse phase, specifically a flow rate ratio of 5: 1 or more, It is necessary to send the continuous phase in excess.
[0082]
(Example 3)
FIG. 27A shows a microchannel according to the third embodiment of the present invention. The micro channels are formed on a 70 mm × 40 mm × 1 t (thickness) Pyrex (registered trademark) glass, a continuous phase introduction channel (3), a dispersed phase introduction channel (5), and a discharge channel corresponding to the micro channels. (7) each had a width of 146 μm, a depth of 55 μm, an aspect ratio of the microchannel = 0.38, a length of the discharge channel of 30 mm, and a continuous phase introduction channel and a dispersed phase introduction channel of 44 °. And a part of the width of the discharge channel as shown in the enlarged view of FIG. 27 (b) is formed as a projection at the junction of the dispersed phase introduction channel and the discharge channel. A Y-shaped channel was formed. The width and depth of the microchannel depend on the particle size of the generated microparticles, but it is sufficient that the aspect ratio of the microchannel does not deviate from the range of 0.30 or more and less than 3.0. The size of the protrusion may be appropriately adjusted depending on the particle size of the fine particles and the pumping ability for the internal pressure of the introduction channel. In this case, the width KK ′ shown in FIG. 27B is 116 μm. The microchannel structure having the microchannel was manufactured in the same manner as in Example 1.
[0083]
Next, the microchannel structure was held by a holder, and a mixed solution of divinylbenzene and butyl acetate was used as a dispersed phase for generating microparticles in the same manner as in Example 1, and a 3% aqueous solution of polyvinyl alcohol was used as a continuous phase. The liquid is injected into a microsyringe, and the liquid is sent by a microsyringe pump. The liquid is supplied through a flow path having no projection shown in FIG. 27 (c) at the intersection of the continuous phase introduction flow path, the dispersed phase introduction flow path and the discharge flow path. A comparison was made. The liquid sending speed was the same for both the dispersed phase and the continuous phase, and the flow rate at which fine particles could be generated was measured. The flow rate at which fine particles could be generated at the microchannel structure having protrusions was 10 μl / min. In the case of the microchannel structure having no projection as shown in (c), the flow rate was 8 μl / min.
Observing the microparticles generated in the microchannel structure having protrusions, the average particle diameter is 110 μm, and the CV value (%) indicating the degree of dispersion of the particle diameter is 6.3%. Have been obtained. This makes it possible to maintain a good degree of dispersion and increase the amount of generated fine particles by providing projections in the discharge flow path.
[0084]
(Example 4)
FIG. 28 shows a microchannel according to the fourth embodiment of the present invention. The microchannel is composed of two continuous phase introduction channels (3) and one dispersed phase introduction channel (3) corresponding to the microchannel on Pyrex (registered trademark) glass of 70 mm × 20 mm × 1 t (thickness). 5) and the width of the discharge channel (7) are both 140 μm, the depth is 60 μm, the aspect ratio of the microchannel is 0.43, the length of the discharge channel is 30 mm, and the continuous phase introduction channel and the dispersed phase introduction. One flow path having a confluent portion each intersecting at an angle of 22 ° was formed so that the flow path sandwiched one dispersed phase introduction flow path with two continuous phase introduction flow paths. The width and depth of the microchannel depend on the particle size of the generated microparticles, but it is sufficient that the aspect ratio of the microchannel does not deviate from the range of 0.30 or more and less than 3.0. Note that this microchannel structure was manufactured in the same manner as in Example 1.
[0085]
Next, a microchannel structure was held by a holder in the same manner as in Example 1, and a mixed solution of divinylbenzene and butyl acetate was added to the dispersed phase for generating microparticles in the same manner as in Example 1; , A 3% aqueous solution of polyvinyl alcohol was injected into the microsyringe, and the solution was sent by a microsyringe pump. The dispersed phase was introduced from the central dispersed phase introduction channel, and the continuous phase was introduced from the continuous phase introduction channels on both sides of the dispersed phase introduction channel. The liquid sending speed is 6 μl / min for both the dispersed phase and the continuous phase. In a state where the liquid sending speeds were both stable, generation of fine particles was observed at the junction where the dispersed phase and the continuous phase of the fine channel structure for manufacturing fine particles intersect. Observation of the generated fine particles revealed that the average particle size was 77 μm, and the CV value (%) indicating the degree of dispersion of the particle size was 7.0%, indicating that the particles were extremely uniform.
[0086]
(Example 5)
As a fifth embodiment, a microchannel structure having four channels as shown in FIG. 29 was manufactured. The formed microchannel (16) has a width of 100 μm and a depth of 40 μm, and is connected to the fluid inlet A (43), the fluid inlet B (44), the fluid inlet C (45), and the fluid inlet. The laminar flow channel (46) and the micro flow channel connected to the laminar flow channel were respectively joined at an angle of 44 °. A microchannel structure having this microchannel was manufactured in the same manner as in Example 1. A mixed solution of organic phase divinylbenzene and butyl acetate is sent as a dispersed phase from the fluid inlet A of the microchannel, and a 3% aqueous solution of polyvinyl alcohol in the aqueous phase is sent from the fluid inlet B. From the inlet C, a 3% aqueous polyvinyl alcohol aqueous solution was fed as a continuous phase. The liquid was supplied to the microsyringe in the same manner as in Example 1, and the liquid was sent using a microsyringe pump. The liquid was sent at a rate of 5 μl / min from the fluid inlet A and the fluid inlet B and at 10 μl / min from the fluid inlet C. Laminar flow was observed from the laminar junction (47) of the fluid introduction ports A and B to the junction (6) in a state where the liquid sending speeds were both stable. Also, generation of fine particles was confirmed at the junction of the continuous phases. Observation of the generated fine particles showed that the average particle size was 110 μm, and the CV value (%) indicating the degree of dispersion of the particle size was 8.2%, indicating uniform fine particles.
[0087]
(Example 6)
FIG. 20 shows a microchannel in the sixth embodiment of the present invention. The microchannels are formed on a Pyrex (registered trademark) glass of 70 mm × 20 mm × 1t (thickness), and the continuous phase introduction channel (3), the dispersed phase introduction channel (5), and the discharge channel corresponding to the microchannels. (7) The width of each is 220 μm, the depth is 80 μm, the aspect ratio of the microchannel is 0.36, the length of the discharge channel is 30 mm, and the continuous phase introduction channel and the dispersed phase introduction channel are 44 °. One Y-shaped flow path having a merging portion that intersects at an angle is formed. The width and depth of the microchannel depend on the particle diameter of the droplets or microparticles to be generated, but the aspect ratio of the microchannel may be within the range of 0.30 or more and less than 3.0. .
In the same manner as in Example 1, a mixed solution of divinylbenzene and butyl acetate was injected into a dispersed phase for producing fine particles, and a 3% aqueous solution of polyvinyl alcohol was injected into a continuous phase into each microsyringe. Performed with a syringe pump. The liquid sending speed is 2 μl / min for both the dispersed phase and the continuous phase. With both the liquid sending speeds stable, generation of fine particles was observed at the junction where the dispersed phase and the continuous phase of the microchannel structure intersect. After the generation of the fine particles, as shown in FIG. 8 (b), the position of the discharge channel (7) 10 mm away from the discharge port (8) is set as the center of the light irradiation spot (20), and the light irradiation (21) by ultraviolet light is performed. The microparticles were cured. The size of the light irradiation spot was about 10 mm in diameter. A mask (22) was provided so that light irradiation was not performed on portions other than the light irradiation spot. From the outlet, fine particles were discharged using an aqueous solution of polyvinyl alcohol as a medium. Observation of the generated fine particles revealed that the average particle size was 200 μm, and the CV value (%) indicating the degree of dispersion of the particle size was 8.5%, which was extremely uniform. Also, instead of irradiating light after generating the microparticles in the microseparator, a portion of the Teflon (registered trademark) tube (27) outside the microchannel structure from the outlet (8) shown in FIG. Was heated to 65 ° C. by a heater (28) to cure the fine particles. Fine particles using an aqueous solution of polyvinyl alcohol as a medium were discharged to the beaker (26). Observation of the generated fine particles revealed that the CV value (%) indicating the degree of dispersion of the particle diameter was 8.5%, with an average particle diameter of 200 μm, which was extremely uniform.
[0088]
(Example 7)
As a seventh example, a microchannel structure having a microchannel (16) as shown in FIG. 30 was manufactured. The position of the common flow channel inlet such that the flow channel depth is 80 μm and the flow channel width is 0.5 mm at the position of the common flow channel inlet (32) and 2 mm at the position of the common flow channel outlet (31). From the two common flow paths (29) whose flow path widths are gradually increased toward the position of the common flow path discharge port, a micro flow path having a width of 220 μm and a depth of 80 μm is drawn out and merged in a Y-shape. Four channels are placed at regular intervals of 6 mm (a ₁ ~ A ₅ Are all 6 mm). The shape of the Y-shaped minute flow path is the same as that of the first embodiment. The common channel inlet was 0.5 mm wide and 80 μm deep, and the common channel outlet was 200 μm wide and 80 μm deep. The microchannel structure having the microchannel was manufactured in the same manner as in Example 1.
[0089]
Pure water is supplied to each of the two common flow paths of the micro flow path structure at a flow rate of 2.5 ml / min for 5 minutes to each of the common flow paths in the same manner as in the first embodiment. The amount of liquid discharged from the fluid discharge port of the micro flow path after passing through the Y-shaped micro flow path was compared in each flow path, and the results shown in Table 1 were obtained. ₁ ~ Y ₄ The liquid could be sent uniformly to each of the microchannels.
[0090]
[Table 1]

Further, a 3% aqueous solution of polyvinyl alcohol was sent to one common channel, and a mixed solution of divinylbenzene and butyl acetate was sent to the other common channel at a rate of 100 μl / min in the same manner as in Example 1. As a result of measuring and averaging the particle diameters of the ten microparticles generated in the flow channel with a microscope, the results shown in Table 2 were obtained, and the average value of the particle diameter of the fine particles discharged from each microchannel was 101. The CV value (%) indicating 0 μm and the degree of dispersion of the particle diameter was 8.7%, and uniform microparticles could be generated in each microchannel.
[0091]
[Table 2]

(Comparative Example 2)
As a second comparative example, a microchannel structure having a microchannel (16) as shown in FIG. 31 was manufactured. The position of the common flow channel inlet such that the flow channel depth is 80 μm and the flow channel width is 2 mm at the position of the common flow channel inlet (32) and 0.5 mm at the position of the common flow channel outlet (31). From the two common flow paths (29) whose width is gradually narrowed toward the position of the common flow path discharge port, a minute flow path having a width of 220 μm and a depth of 80 μm was drawn out and merged in a Y-shape. Four micro channels are placed at equal intervals of 6 mm (a ₁ ~ A ₅ Are all 6 mm). The shape of the microchannel is the same as that of the first embodiment. The common channel inlet was 0.5 mm wide and 80 μm deep, and the common channel outlet was 220 μm wide and 80 μm deep. The microchannel structure having the microchannel was manufactured in the same manner as in Example 1.
[0092]
Pure water was supplied to each of the two common channels of the microchannel structure at a flow rate of 2.5 ml / min using a liquid feed pump in the same manner as in the first embodiment. The liquid was sent for 5 minutes, passed through the Y-shaped fine flow path, and the amount of liquid discharged from the fluid discharge port of the fine flow path was compared in each flow path. The result shown in Table 1 was obtained. ₁ ~ Y ₄ The liquid could not be sent uniformly to each of the microchannels.
[0093]
In addition, a 3% aqueous solution of polyvinyl alcohol was sent to one common channel, and a mixed solution of divinylbenzene and butyl acetate was sent to the other common channel at 100 μl / min by a liquid sending pump as in Example 1. As a result of measuring and averaging the particle diameters of ten microparticles generated in each microchannel with a microscope, the results shown in Table 2 are obtained, and microparticles having a uniform particle diameter are generated in each microchannel. I couldn't do that.
[0094]
(Example 8)
As an eighth embodiment, a microchannel structure having microchannels as shown in FIG. 20 was manufactured. The width W of the formed microchannel is 220 [μm], the depth d of the microchannel is 80 [μm], the length of the microchannel is 30 [mm], and two microchannels connected to the inlet (11) are provided. Were joined at an angle of 44 °. The microchannel structure having the microchannel was manufactured in the same manner as in Example 1.
[0095]
In the same manner as in Example 1, an aqueous phase containing phenol as a substance to be extracted was sent from one of the fluid inlets of the microchannel, and ethyl acetate as an extraction solvent was sent from the other fluid inlet. The organic phase was sent. Experiments were carried out when the laminar flow was formed to extract phenol on the ethyl acetate side by adjusting the liquid sending rate, and when the organic phase of ethyl acetate was formed into fine particles and extracted with the aqueous phase. The liquid sending speed when the laminar flow was formed was 20 μl / min for both the aqueous phase and the organic phase. When the organic phase of divinylbenzene was made into fine particles by the aqueous phase, the liquid sending speed was 2 μl / min for both the aqueous phase and the organic phase.
[0096]
In this microchannel, the relative boundary area obtained when a laminar flow is formed is 2 × 10 because the width W of the microchannel is about 220 [μm]. ⁴ / W [cm ^-1 ] = About 2 × 10 ⁴ / 220 [cm ^-1 ] = About 90 [cm] ^-1 ]. The average particle size of the fine particles when the organic phase of ethyl acetate was made fine particles by the aqueous phase was measured using a high-speed camera, and the diameter D of the fine particles was determined to be about 200 [μm]. The relative area in this case is 6 × 10 ⁴ / D [cm ^-1 ] = About 6 × 10 ⁴ / 200 [cm ^-1 ] = About 300 [cm] ^-1 ]. From this, it is presumed that when the organic phase of ethyl acetate was made into fine particles by the aqueous phase, the non-boundary area became larger and the extraction efficiency was increased than when the laminar flow was formed by the aqueous phase and the organic phase. You.
[0097]
Actually, the fluid discharged from the fluid outlet was collected in a test tube, only the organic phase was taken out, and the phenol concentration was measured using high performance liquid chromatography. The longer the time the organic phase and the aqueous phase are in contact, the greater the amount of substance extracted, so the measurement result is calculated based on the residence time in the microchannel calculated from the liquid sending rate of the organic phase as the extraction solvent. Divided and corrected. As a result, the concentration of phenol was higher when the organic phase of ethyl acetate was finely divided and extracted. From the above, it was confirmed that by making the extraction solvent into fine particles, the extraction efficiency was improved beyond the efficiency determined by the width of the microchannel.
[0098]
【The invention's effect】
In the method for producing microparticles of the present invention, a dispersed phase and a continuous phase are introduced into a microchannel structure having a microchannel from its introduction channel, and the dispersed phase is sheared in the continuous phase at a junction where the two are merged to form a microparticle. Particles are generated, and the diameter of the generated fine particles is controlled by changing the angle at which the introduction flow path for introducing the dispersed phase and the introduction flow path for introducing the continuous phase intersect. Is possible. This is easier to control in the production of microparticles using a conventional microchannel structure than changing the introduction speed of the dispersed phase and continuous phase, and is suitable for industrial mass production. In particular, when the introduction speed of the dispersed phase and the introduction speed of the continuous phase are substantially the same, it is sufficient in terms of cost, such as preparing one introduction device. Therefore, by the method for producing microparticles of the present invention, the generation of microparticles having a stable particle size eliminates the need to supply an excessive amount of continuous phase. Becomes possible.
[0099]
Further, by providing an introduction channel for introducing a plurality of dispersed phases and / or continuous phases, the dispersed phase and / or the continuous phase can be formed into a laminar flow of a plurality of fluids, or a mixed solution or suspension (emulsion). By doing so, microparticles having a multilayer structure or microparticles containing various types of microparticles can be formed, and composite microcapsules and multiple microcapsules can be produced.
[0100]
Also, when the microparticles generated at the confluence of the microchannels are microdroplets and the microdroplets are cured, the microdroplets pass through the discharge channel to make the particle size of the hardened microparticles uniform. After exiting from the discharge part, the discharge part of the fine flow path structure may be sequentially and sequentially cured in a fine flow path provided outside the micro flow path structure, and the particles of the hardened fine particles may be further cured. In order to make the diameter more uniform, immediately after the microdroplets are generated at the confluence of the microchannels, they may be hardened in the microchannels, that is, the discharge channels in the microchannel structure, and this is done. If the microparticles generated at the confluence of the microchannels are microdroplets, they are collected in a beaker or the like outside the microchannels, and when the microdroplets are cured by crosslinking polymerization, the microdroplets are collected. Before curing, the shape of the microparticles collapses, or coalescence of the microparticles occurs Because, there is no the variation of the particle diameter of the cured microparticles is large, it is possible particle size to obtain a uniform fine particles. Further, the hardening of the microdroplets facilitates separation from the medium.
In addition, as a mode for producing a large amount of microparticles by parallelizing and / or laminating a large number of the microchannels, an inlet for introducing a fluid and an outlet for discharging the fluid are provided. A microchannel structure having a common channel communicating with the inlet and the outlet on the substrate, and one or more microchannels communicating with the common channel at a position different from the inlet and the outlet. Wherein the cross-sectional area of the common flow path is gradually increased from the communication position with the introduction port toward the communication position with the discharge port or is the same as that of the micro-flow path structure, It is possible to uniformly distribute the fluid to a plurality of micro flow channels arranged two-dimensionally or three-dimensionally.
[0101]
Examples of the use of the fine particles produced by the method for producing fine particles of the present invention include a filler for a column for high performance liquid chromatography, an adhesive such as a seal lock agent, insulating particles of metal particles, a pressure measurement film, Carbon (pressure-sensitive copying) paper, toner, thermal expansion agent, heat medium, light control glass, gap agent (spacer), thermochromic (thermosensitive liquid crystal, thermosensitive dye), magnetophoretic capsule, pesticide, artificial feed, artificial seed , Fragrance, massage cream, lipstick, vitamin capsules, activated carbon, enzyme-containing capsules, microcapsules and gels such as DDS (drug delivery system).
[0102]
Further, in the solvent extraction method using the microchannel structure of the present invention, the efficiency of the reaction and extraction is determined by the width of the microchannel by using the microparticles for solvent extraction in the microchannel. The above can be improved.
[Brief description of the drawings]
FIG. 1 is a schematic view showing a conventional microchannel for generating microparticles. FIG. 1R is a cross-sectional view taken along line AA ′ of FIG. FIG.
2 (a) is a conceptual diagram showing a laminar flow in a Y-shaped microchannel, and FIG. 2 (b) is an enlarged three-dimensional cross section of a circle which is a part of FIG. 2 (a). FIG.
FIG. 3 is a conceptual diagram showing a method in which a continuous phase shears a dispersed phase to form microparticles near a confluence of a microchannel.
FIG. 4 is a conceptual diagram showing a method of forming microparticles by shearing a continuous phase on both sides so as to sandwich a central dispersed phase in the vicinity of a confluence of a microchannel.
FIG. 5 is a conceptual diagram showing a method in which a central continuous phase shears dispersions on both sides to form fine particles in the vicinity of a merging portion of a microchannel.
FIG. 6: In the vicinity of the confluence of the microchannel, a dispersed phase is linearly introduced from one side and a continuous phase is introduced from the other side, and the dispersed phase is sheared by the continuous phase to generate microparticles. It is a conceptual diagram showing a method of discharging in the direction of.
FIG. 7 is a diagram illustrating a disperse phase introduction channel for introducing a plurality of dispersed phases and / or continuous phases and / or a continuous phase introduction channel for laminar flow or mixing of a dispersed phase and / or a continuous phase with a plurality of fluids. FIGS. 7A to 7C are some conceptual diagrams showing a method of forming a microparticle by shearing a dispersed phase in a continuous phase in the vicinity of a confluence of a microchannel as a liquid or a suspension (emulsion). g) shows each embodiment.
8A and 8B are schematic views showing a method for curing fine particles by light irradiation. FIG. 8A shows a case where light irradiation means is provided outside, and FIG. 8B shows light irradiation using a mask. FIG.
9A and 9B are schematic views showing a method of curing microparticles by heating. FIG. 9A shows a case where a heating unit is provided outside, and FIG. 9B shows a case where the heating unit is provided inside the microchannel structure. It is a schematic diagram in the case of having provided.
FIG. 10 is a conceptual diagram showing the most basic shape of a microchannel for uniformly sending a fluid to a plurality of microchannels arranged two-dimensionally or three-dimensionally.
FIG. 11 is a cross-sectional view showing a cross section of a common flow channel from a common flow channel introduction port to a common flow channel discharge channel in a micro flow channel shape for uniformly sending a fluid to a plurality of micro flow channels arranged two-dimensionally or three-dimensionally. It is the conceptual diagram which showed the example which becomes large gradually toward an exit.
FIG. 12 is a schematic view showing a microchannel shape for uniformly sending a fluid to a plurality of microchannels arranged two-dimensionally or three-dimensionally. It is the conceptual diagram which showed the example which sent liquid.
FIG. 13 is a conceptual diagram showing an example in which a common flow path is arranged in an arc shape among fine flow path shapes for uniformly sending a fluid to a plurality of fine flow paths arranged two-dimensionally or three-dimensionally. .
FIG. 14 is a view showing a structure in which a microchannel substrate having microchannels is overlapped and a common channel is formed in a microchannel shape for uniformly sending a fluid to a plurality of microchannels arranged two-dimensionally or three-dimensionally. This is an example in which the microchannel substrate is penetrated, and the upper part of FIG. 14 is a cross-sectional view taken along the line DD ′ and EE ′, showing the lamination integration.
FIG. 15 is a conceptual diagram showing microparticles in a microchannel.
FIG. 16 is a microparticle according to the present invention when the fluid containing the substance to be extracted is a fluid in which two fluids having raw materials are separately introduced into a microchannel and mixed and reacted in a reaction phase in the microchannel. FIG. 3 is a conceptual diagram of a solvent extraction method as a use of the method.
FIG. 17: In a microchannel for generating a product by a reaction occurring at a fluid boundary, two fluids having raw materials are made into a continuous phase, and the extraction solvent is sheared at the fluid boundary by the continuous phase, so that the microfluid is formed at the fluid boundary. It is a conceptual diagram which extracts the product produced | generated at the fluid boundary by forming a droplet and making it into a dispersed phase.
FIG. 18 shows that a fluid containing a substance to be extracted is converted into fine droplets to form a dispersed phase, and a phase is transferred to an extraction solvent that is a continuous phase to perform solvent extraction, and then at least the surface of the fine droplets is cured. It is a conceptual diagram which shows separating an to-be-extracted substance.
FIG. 19 shows that a fluid containing a substance to be extracted is made into a continuous phase, and the solvent is extracted by performing phase-to-phase transfer to an extraction solvent that has been formed into microdroplets to form a dispersed phase, and then at least the surface of the microdroplets is cured. It is a conceptual diagram which shows separating an to-be-extracted substance.
FIG. 20 is a schematic view showing a microchannel in Examples 1, 6 and 8.
FIG. 21 is a schematic view showing a microchannel structure in Example 1.
FIG. 22 is a schematic diagram showing a method for producing fine particles in Example 1.
FIG. 23 is a schematic view showing a state of generating fine particles in Example 1.
FIG. 24 is a diagram showing the generated fine particles in Example 1.
25 is a schematic diagram showing a microchannel in Example 2, and FIG. 25 right is a cross-sectional view taken along line GG ′ of FIG. 25 left.
26 is a schematic view showing a microchannel in Comparative Example 1, and the right side of FIG. 26 is a cross-sectional view taken along line HH ′ of HH ′ on the left side of FIG.
27 (a) is a schematic view showing a microchannel in Example 3, and FIGS. 27 (b) and 27 (c) are enlarged views of a portion 6 in FIG. 27 (a). .
28 is a schematic diagram showing a microchannel in Example 4, and FIG. 28 right is a cross-sectional view taken along line MM ′ of line MM ′ in FIG. 28 left.
29 is a schematic diagram showing a microchannel in Example 5, and FIG. 29 right is a cross-sectional view taken along line NN ′ of NN ′ shown in FIG. 29 left.
FIG. 30 is a schematic view of the shape of the microchannel shown in Example 7.
FIG. 31 is a schematic view of the shape of the microchannel shown in Comparative Example 2.
FIGS. 32 (a) to (e) are some conceptual diagrams showing examples in which one or more projections are formed from any one or more of the bottom, top, and side surfaces of a flow channel. It is.
[Explanation of symbols]
1: Microchannel substrate
2: Continuous phase inlet
3: Continuous phase introduction channel
4: Dispersed phase inlet
5: Dispersed phase introduction channel
6: junction
7: discharge channel
8: outlet
9: Width of micro channel
10: continuous phase
11: Inlet
12: Organic phase
13: Water phase
14: Fluid boundary
15: Disperse phase
16: micro channel
17: microparticle
18: diameter of microparticle
19: Microchannel structure
20: Light irradiation spot
21: Light irradiation
22: Mask
23: Holder
24: Unit length of microchannel
25: Depth of micro channel
26: Beaker
27: Teflon (registered trademark) tube
28: heater
29: Common channel
30: Cover body
31: Common channel outlet
32: Common channel inlet
33: diameter of microdroplet
34: micro droplet
35: Fluid A
36: Fluid b
37: Reaction phase
38: Extraction solvent
39: Solvent extraction
40: Fillet joint
41: Micro syringe pump
42: Micro syringe
43: Fluid inlet A
44: Fluid inlet B
45: Fluid inlet C
46: Laminar flow channel
47: Laminar junction
48: Introductory channel

Claims (41)

An introduction port and an introduction flow path for introducing a dispersed phase, an introduction port and an introduction flow path for introducing a continuous phase, a discharge flow path for discharging fine particles generated by the dispersed phase and the continuous phase, and A microchannel structure comprising a microchannel having an outlet, and the introduction channel for introducing the dispersed phase and the introduction channel for introducing the continuous phase intersect at an arbitrary angle, A microchannel structure wherein the two introduction channels are connected to a discharge channel at an arbitrary angle. 2. The microchannel structure according to claim 1, wherein an aspect ratio (ratio of depth / width of the channel) of the channel cross section is 0.30 or more and less than 3.0. 3. 3. The microchannel structure according to claim 1, wherein the width and depth of the introduction channel for introducing the dispersed phase and the introduction channel for introducing the continuous phase are equal. The microchannel structure according to any one of claims 1 to 3, wherein, in the relationship between the width of the introduction channel and the width of the discharge channel, the width of the introduction channel ≥ the width of the discharge channel. . The width of the discharge channel is reduced at a part of the discharge channel from the intersection of the dispersed phase and the continuous phase to the discharge port, wherein the width of the discharge channel is reduced. The microchannel structure according to any one of the preceding claims. 6. The microchannel structure according to claim 5, wherein the portion where the width of the discharge channel is narrowed is at or near an intersection in the discharge channel. 7. The microchannel structure according to claim 5, wherein the portion where the width of the discharge channel is narrow is located at the crossing portion of the discharge channel on the side of the introduction channel of the dispersed phase. 8. One or more protrusions are formed from the bottom surface, the top surface, and / or the side surface of the flow channel in the vicinity of the position where the dispersed phase and the continuous phase have joined. Micro channel structure. An inlet for introducing a fluid and an outlet for discharging the fluid, a common flow path communicating with the inlet and the outlet on the substrate, and the common channel at a different position from the inlet and the outlet. A microchannel structure having at least one microchannel communicating with the channel, wherein a cross-sectional area of the common channel gradually increases from a position communicating with the inlet toward a position communicating with the outlet. Or a microchannel structure characterized by being the same or the same. Communication position with the in microchannels n present the fine channel Y ₁ is closest to the inlet to the nearest fine channel Y _n to the outlet common passage and communication with fine channel, inlet Is X ₀ , the communication position of the micro flow path Y ₁ closest to the inlet is X ₁ , the length along the common flow path between X ₀ and X ₁ is a ₁ , and the communication position with the discharge port is X _{n + 1,} the communicating position _X n nearest fine channel _{Y n} to the outlet, when the common flow path lengths along between _{X n} and _{X n + 1} was _{a n + 1, a n} is everything from _{a 2} The microchannel structure according to claim 9, wherein the microchannel structure is equal. fine channel according to claim 10, wherein a ₁ ~a _{n + 1} is characterized in that all equal. 10. The microchannel structure according to claim 9, wherein one or more microchannel substrates having microchannels are overlapped, and a common channel penetrates the microchannel substrate. 12. The microchannel structure according to any one of items 11 to 11. 13. The microchannel according to claim 9, wherein the microchannel structure has a structure in which a fluid discharged from an outlet of each common channel is returned to each inlet. Channel structure. The microchannel structure according to any one of claims 9 to 13, wherein the microchannel structure has a plurality of common channels, and each common channel communicates with the microchannel. body. 15. The microchannel structure according to claim 14, wherein a dispersed phase is introduced into at least one of the common channels of the microchannel structure, and a continuous phase is introduced and discharged into at least another one of the common channels. An introduction port and an introduction flow path for introducing a dispersed phase, an introduction port and an introduction flow path for introducing a continuous phase, a discharge flow path for discharging fine particles generated by the dispersed phase and the continuous phase, and A method for producing microparticles using a microchannel structure provided with an outlet, wherein the dispersion phase is converted into microparticles by merging a dispersed phase and a continuous phase. . 17. The particle size of the microparticles generated by changing the angle at which the introduction channel for introducing the dispersed phase and the introduction channel for introducing the continuous phase intersect is controlled, according to claim 16, wherein A method for producing fine particles. 18. The method for producing fine particles according to claim 16, wherein the introduction speed of the dispersed phase and the introduction speed of the continuous phase are substantially the same. 19. The method for producing fine particles according to claim 16, wherein the fluid containing the generated fine particles is discharged in an arbitrary direction from a position where the continuous phase and the dispersed phase have joined. 20. Microparticle production according to any one of claims 16 to 19, wherein the fluid containing the generated microparticles is discharged in any two or more directions from a position where the continuous phase and the dispersed phase merge. Method. 21. The method for producing fine particles according to claim 20, wherein the fluid containing the generated fine particles is combined again and collected. The method according to any one of claims 16 to 21, wherein the continuous phase and the dispersed phase are substantially incompatible fluids. The method according to any one of claims 16 to 22, wherein the continuous phase and / or the dispersed phase are laminar flows composed of two or more fluids. The method according to any one of claims 16 to 23, wherein the continuous phase and / or the dispersed phase is a fluid composed of a mixture or suspension (emulsion) of two or more fluids. The method for producing fine particles according to any one of claims 16 to 24, wherein the continuous phase and / or the dispersed phase contains fine powder. The method for producing fine particles according to any one of claims 16 to 25, wherein the dispersed phase is a medium containing a raw material for producing a gel. The method for producing fine particles according to any one of claims 16 to 26, wherein the continuous phase is a medium containing a dispersant for producing a gel. The method for producing microparticles according to any one of claims 16 to 27, wherein the gel producing dispersant is polyvinyl alcohol. The method for producing microparticles according to any one of claims 16 to 28, wherein the microparticles are microdroplets. The method for producing microparticles according to any one of claims 16 to 29, wherein the microparticles are cured in the microchannel and / or outside the microchannel. The method for producing fine particles according to claim 30, wherein the fine particles are cured by irradiating light. The method for producing microparticles according to claim 31, wherein the microparticles are cured by irradiating the microparticles with ultraviolet rays. The method for producing fine particles according to claim 30, wherein the fine particles are cured by heating. The dispersed phase is a medium containing a raw material for gel production, and an inlet and an introduction channel for introducing the dispersed phase, and the continuous phase is a medium containing a dispersant for gel production, and introduced for introducing a continuous phase. A method for producing microparticles using a microchannel structure provided with a mouth and an introduction channel, and a discharge channel and a discharge port for discharging microparticles generated by the dispersed phase and the continuous phase, The dispersion phase and the continuous phase are merged to form the dispersed phase into fine particles. A method for producing microparticles, comprising controlling the particle size of microparticles to be formed, and curing the microparticles by light irradiation and / or heating in and / or outside the microchannel. The method for producing fine particles according to any one of claims 16 to 34, wherein the fine particles are microcapsules. The method for producing fine particles according to any one of claims 16 to 34, wherein the fine particles are a gel. A dispersion phase comprising the microdroplets after using the microchannel structure according to any one of claims 1 to 15 to convert a fluid containing an extraction solvent or a substance to be extracted into microdroplets in the microchannels. Use of the microparticles as a solvent extraction method, wherein solvent extraction is performed by interphase movement of a substance to be extracted between the microparticles and a continuous phase surrounding the microdroplets. The use of the microparticles as a solvent extraction method according to claim 37, wherein in the solvent extraction method, the fluid containing the substance to be extracted is a continuous phase, and the extraction solvent is a dispersed phase. The use of the microparticles as a solvent extraction method according to claim 37, wherein in the solvent extraction method, the fluid containing the substance to be extracted is a dispersed phase, and the extraction solvent is a continuous phase. The use of the microparticles as a solvent extraction method according to any one of claims 37 to 39, wherein the substance to be extracted is a product obtained by chemically reacting two or more fluids containing raw materials. . After performing the solvent extraction in the microchannel, the continuous phase and the dispersed phase are separated by hardening at least the surface of the microdroplet by the microparticle production method according to any one of claims 29 to 33. The use of the microparticles as the solvent extraction method according to any one of claims 37 to 40.

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