JP4547967B2 - Microchannel structure and droplet generation method using the same - Google Patents

Microchannel structure and droplet generation method using the same Download PDF

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JP4547967B2
JP4547967B2 JP2004118970A JP2004118970A JP4547967B2 JP 4547967 B2 JP4547967 B2 JP 4547967B2 JP 2004118970 A JP2004118970 A JP 2004118970A JP 2004118970 A JP2004118970 A JP 2004118970A JP 4547967 B2 JP4547967 B2 JP 4547967B2
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達 二見
恵一郎 西澤
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本発明は、分取・分離用カラム充填剤に用いられる微小粒子や医薬品、含酵素カプセル、化粧品、香料、表示・記録材料、接着剤、農薬等に利用されるマイクロカプセルに用いられる微小粒子などの製造用として好適に用いられる微小流路構造体及びそれを用いた微小な液滴生成方法に関する。   The present invention includes fine particles used in column fillers for sorting and separation, fine particles used in microcapsules used in pharmaceuticals, enzyme-containing capsules, cosmetics, fragrances, display / recording materials, adhesives, agricultural chemicals, etc. The present invention relates to a micro flow channel structure that is preferably used for manufacturing a liquid crystal and a micro droplet generation method using the micro channel structure.

近年、数cm角のガラス基板上に長さが数cm程度で、幅と深さがサブμmから数百μmの微小流路を有する微小流路構造体を用い、流体を微小流路へ導入することにより微小粒子の生成を行う研究が注目されている。微小粒子を生成する手段の一つとして、界面張力の異なる2種類の流体を、前記2種類の流体の交差部が存在する流路に導入し、一方の流体によりもう一方の流体をせん断することにより微小粒子を生成することができることが報告されている(例えば、特許文献1参照)。なおここでいう微小粒子とは、固体状の微小粒子の他にも微小液滴や微小液滴の表面だけが硬化した微小粒子(以下、「半硬化」という。)や、非常に粘性が高い半固体状の微小粒子も含む。   In recent years, a fluid is introduced into a microchannel using a microchannel structure having a microchannel having a length of about several centimeters on a glass substrate of several cm square and a width and depth of sub-μm to several hundred μm. Research that produces microparticles by doing so has attracted attention. As one of the means for generating fine particles, two kinds of fluids having different interfacial tensions are introduced into a flow path where the intersection of the two kinds of fluids exists, and one fluid is sheared by the other. It has been reported that microparticles can be generated by the above (for example, see Patent Document 1). The microparticles here are solid microparticles, microdroplets, microparticles obtained by curing only the surface of microdroplets (hereinafter referred to as “semi-cured”), and extremely high viscosity. Also includes semi-solid fine particles.

例えば、特許文献1に示されている手法は図1に示すように、基板(1)に連続相導入口(2)、連続相を導入する流路(以下、連続相導入流路(3)という)、分散相導入口(4)、分散相を導入する流路(以下、分散相導入流路(5)という)、連続相中に微小粒子化した分散相を排出する流路(以下、排出流路(7)という)及び排出口(8)を有したT字型の流路を有し、基板の流路面側にカバー体を接合した微小流路構造体であり、マイクロチャンネル中を流れる連続相に対し、分散相を前記連続相の流れに交差する向きで分散相供給口より排出し、前記連続相のせん断力によって、前記分散相の供給チャンネルの幅より径の小さい微小液滴を得ている。なお、図1の流路の一部断面図を図2に示した。ここで特許文献1には、連続相導入流路の幅及び分散相導入流路の幅は100μmであり、連続相導入流路の深さ及び分散相導入流路の深さは100μmと記載されている。なお、以下では、導入された連続相と分散相とが交差する部分を交差部(6)という。 特許文献1に記載された手法を用い分散相と連続相の流速を制御して送液を行うと、数μm〜数百μmの微小液滴の生成が可能であり、分散相及び連続相の流量を制御することで生成する微小液滴の粒径を制御することが可能であることが記載されている。得られた微小液滴の粒径としては、特許文献1では分散相の送液圧を2.45kPaに固定し、連続相の送液圧を4.85〜5.03kPaに変化させることで5〜25μmの粒径の微小液滴を得ていることが示されている。   For example, as shown in FIG. 1, the technique disclosed in Patent Document 1 is a continuous phase introduction port (2) and a flow path for introducing a continuous phase (hereinafter referred to as a continuous phase introduction flow path (3)) to a substrate (1). Disperse phase introduction port (4), a flow path for introducing the disperse phase (hereinafter referred to as disperse phase introduction flow path (5)), a flow path for discharging the disperse phase dispersed into the continuous phase (hereinafter referred to as “dispersion phase introduction flow path”) A micro-channel structure having a T-shaped channel having a discharge channel (7) and a discharge port (8) and having a cover member joined to the channel surface side of the substrate. With respect to the flowing continuous phase, the dispersed phase is discharged from the dispersed phase supply port in a direction crossing the flow of the continuous phase, and by the shearing force of the continuous phase, a micro droplet having a diameter smaller than the width of the supply channel of the dispersed phase Have gained. A partial cross-sectional view of the flow path of FIG. 1 is shown in FIG. Here, Patent Document 1 describes that the width of the continuous phase introduction channel and the width of the dispersed phase introduction channel are 100 μm, and the depth of the continuous phase introduction channel and the depth of the dispersed phase introduction channel are 100 μm. ing. Hereinafter, a portion where the introduced continuous phase and the dispersed phase intersect is referred to as an intersection (6). When the liquid feeding is performed by controlling the flow rates of the dispersed phase and the continuous phase using the technique described in Patent Document 1, it is possible to generate micro droplets of several μm to several hundreds of μm. It is described that it is possible to control the particle size of the generated fine droplets by controlling the flow rate. Regarding the particle diameter of the obtained microdroplets, in Patent Document 1, the liquid feeding pressure of the dispersed phase is fixed to 2.45 kPa, and the liquid feeding pressure of the continuous phase is changed to 4.85 to 5.03 kPa. It is shown that microdroplets with a particle size of ˜25 μm are obtained.

しかしながら、流体のせん断力を用いて粒径が10μm未満であり、かつ粒径分散度が良い液滴を生成することは一般的に非常に難しい。ここで、粒径分散度とは、粒径の標準偏差を粒径の平均値(以下、平均粒径という。)で割った値であると定義し、本発明において粒径分散度が良いとは、粒径分散度が10%未満であることを意味する。   However, it is generally very difficult to produce droplets having a particle size of less than 10 μm and a good degree of particle size dispersion using the shear force of the fluid. Here, the particle size dispersion degree is defined as a value obtained by dividing the standard deviation of the particle size by the average value of the particle sizes (hereinafter referred to as the average particle size). Means that the particle size dispersion is less than 10%.

また、微小液滴を生成する別の手段として、2本の流路(以下、流路A、流路Bとする)に挟まれた、前記2本の流路と連通する微小空間に、一方の流路Aから液滴化したい流体を送液し、毛細管現象により前記微小空間に流体を引き込んだ後、流路Aに残留する流体を取り除き、前記微小空間の容積に応じた体積の液滴を生成することが試みられている(例えば、特許文献2参照)。   In addition, as another means for generating microdroplets, a minute space sandwiched between two flow paths (hereinafter referred to as flow path A and flow path B) is connected to the two flow paths. A fluid to be formed into droplets is sent from the channel A, and after the fluid is drawn into the microspace by capillary action, the fluid remaining in the channel A is removed, and a droplet having a volume corresponding to the volume of the microspace is removed. Has been attempted (see, for example, Patent Document 2).

特許文献2に示されている手法は図3に示すように、それぞれ所定の方向に延長される第1の流路A(9)ならびに第2の流路B(10)と、流路Aならびに流路Bのそれぞれの流路壁において開口して流路Aと流路Bとを連結する流路Aならびに流路Bの太さより細い第3の流路C(11)とを有し、流路Aに導入された液体が、流路Aの流路壁において開口する流路Cの開口部を介して毛細管現象により流路C内に引き込まれた後、流路Aに残留する前記液体を取り除き、前記流路Cの容積に応じた体積の液滴を生成し流路Bに送り出している。   As shown in FIG. 3, the technique disclosed in Patent Document 2 includes a first flow path A (9) and a second flow path B (10) that are each extended in a predetermined direction, a flow path A and A flow path A that opens in each flow path wall of the flow path B and connects the flow paths A and B, and a third flow path C (11) that is thinner than the thickness of the flow path B. After the liquid introduced into the channel A is drawn into the channel C by capillary action through the opening of the channel C that opens in the channel wall of the channel A, the liquid remaining in the channel A is removed. The liquid droplets having a volume corresponding to the volume of the flow path C are generated and sent to the flow path B.

前述した特許文献2では、流路Cの容積が実質的にnL(×10−9リットル:ナノリットル)オーダーであり、実施例にも5nLのグルコース水溶液の液滴を生成している。これは粒径に換算すると約200μm程度となる。さらに平均粒径の小さい液滴を生成するには、流路Cの容積を小さくする必要があり、流路Cの容積を0.5pL(×10−12リットル:ピコリットル)未満とすれば平均粒径が10μm未満の液滴を生成することが計算上可能である。しかしながら、0.5pLの断面積は、0.5pLの立方体を仮定した場合約8μmとなる。この態様で液滴を生成した場合、液滴生成速度が遅いという問題がある。以下にその理由を記述する。 In Patent Document 2 described above, the volume of the channel C is substantially on the order of nL (× 10 −9 liters: nanoliters), and droplets of a 5 nL glucose aqueous solution are also generated in the examples. This is about 200 μm in terms of particle size. In order to generate droplets having a smaller average particle size, the volume of the channel C needs to be reduced. If the volume of the channel C is less than 0.5 pL (× 10 −12 liters: picoliter), the average It is computationally possible to produce droplets with a particle size of less than 10 μm. However, the cross-sectional area of 0.5 pL is about 8 μm 3 assuming a 0.5 pL cube. When droplets are generated in this manner, there is a problem that the droplet generation speed is slow. The reason is described below.

一般に空間を流れる流体の圧力損失(ΔP[Pa])は、以下に示す(式1)のハーゲン・ポアズイユの式に従う。   In general, the pressure loss (ΔP [Pa]) of the fluid flowing through the space follows the Hagen-Poiseuille equation (Equation 1) shown below.

ΔP=32μLv/R (式1)
μ[Pa・s]は流体の粘性係数、L[m]は流路長、v[m/s]は流体の線速度、R[m]は流路を円筒管とした場合の流路の直径である。従って、直径R[m]、長さL[m]の円筒管に線速度v[m/s]で送液するときの力F[N]は以下の(式2)で示される。
ΔP = 32 μLv / R 2 (Formula 1)
μ [Pa · s] is the viscosity coefficient of the fluid, L [m] is the channel length, v [m / s] is the linear velocity of the fluid, and R [m] is the channel flow when the channel is a cylindrical tube. Diameter. Therefore, the force F 1 [N] when liquid is fed to a cylindrical tube having a diameter R [m] and a length L [m] at a linear velocity v [m / s] is expressed by the following (formula 2).

=ΔP・πR/4=8πμLv (式2)
一方、毛細管現象で流体が引き込まれる力F[N]は一般に(式3)で示される。
F 1 = ΔP · πR 2/ 4 = 8πμLv ( Equation 2)
On the other hand, the force F 2 [N] at which fluid is drawn by capillary action is generally expressed by (Equation 3).

=πRTcosθ (式3)
T[F/m]は流体の表面張力、R[m]は流路を円筒管とした場合の流路の直径である。
F 2 = πRT cos θ (Formula 3)
T [F / m] is the surface tension of the fluid, and R [m] is the diameter of the channel when the channel is a cylindrical tube.

毛細管現象により流体が流路Cに入りこむためには、毛細管現象で流体が引き込まれる力Fが圧力損失による力Fより大きいことが条件であるので、F>Fである必要があることから(式4)の関係が成り立つ。 In order for the fluid to enter the flow path C by the capillary phenomenon, it is necessary that F 2 > F 1 because the force F 2 at which the fluid is drawn by the capillary phenomenon is greater than the force F 1 due to pressure loss. Therefore, the relationship of (Equation 4) holds.

πRTcosθ>8πμLv (式4)
(式4)を変形して、
vL/R<Tcosθ/8μ (式5)
となる。ここで、ガラス流路に対して水を流路Cに送り込むことを考えると、水の粘性係数μは1[mPa・s]、表面張力Tは26.2[mN/m]、ガラスとの接触角θは0[度]として計算すると、
v<3.275R/L (式6)
となる。
πRTcos θ> 8πμLv (Formula 4)
(Equation 4)
vL / R <T cos θ / 8μ (Formula 5)
It becomes. Here, considering that water is fed into the channel C with respect to the glass channel, the viscosity coefficient μ of water is 1 [mPa · s], the surface tension T is 26.2 [mN / m], When the contact angle θ is calculated as 0 degree,
v <3.275R / L (Formula 6)
It becomes.

今、平均粒径約60μm程度の液滴を生成する場合を考える。この場合、流路Cの体積は、内径Rが50μm、流路長Lが50μmの円筒状の体積に相当する。ガラス流路に対して水を流路Cに送り込む条件は(式6)を満たす必要があるから、RとLを代入すると線速度vは3.275m/s未満である必要がある。ここで、内径R[m]、の円筒状の流路を線速度v[m/s]で流す時の送液速度u[L/分]との関係は以下の(式7)で示される。   Consider a case where droplets having an average particle size of about 60 μm are generated. In this case, the volume of the flow path C corresponds to a cylindrical volume having an inner diameter R of 50 μm and a flow path length L of 50 μm. Since the condition for feeding water into the channel C with respect to the glass channel needs to satisfy (Equation 6), if R and L are substituted, the linear velocity v needs to be less than 3.275 m / s. Here, the relationship with the liquid feeding speed u [L / min] when flowing through a cylindrical flow path having an inner diameter R [m] at a linear velocity v [m / s] is expressed by the following (formula 7). .

u=60π(R/2)・v・10 (式7)
従って、上記の線速度3.275m/s未満の時の送液速度uは385μL/分未満となる。
u = 60π (R / 2) 2 · v · 10 3 (Formula 7)
Therefore, the liquid feeding speed u when the linear speed is less than 3.275 m / s is less than 385 μL / min.

一般に実際の生産量としては、年間約1万Lの液滴をスラリーとして得る場合が考えられる(以下、本発明においては、年間1万Lの液滴を含んだスラリーを生産する程度の能力を大量生産と定義することとする。)。また、マイクロリアクターの特徴として、同じ流路の本数を増やせば液滴の単位時間あたりの生産能力を向上させることができるナンバリングアップという概念が提唱されている。しかしながら、実際にマイクロリアクターを大量生産用にナンバリングアップした報告は本発明者らが実施した例(例えば非特許文献1参照)以外にはほとんど無い。非特許文献1で示されているように、例えば直径130mmの微小流路基板に微小流路を放射状に配置した場合は10〜100本本程度、またその基板を積層した場合も5枚〜10枚程度、その積層したマイクロリアクターを並列に設置したとしても5〜10程度の並列が現時点での実績であり、流路の本数としては最大で1万本程度が現時点での現実的なナンバリングアップと想定できる。前述したマイクロリアクターによる大量生産システムを用いて、実稼動日数を210日、1日8時間送液したとして、年間1万Lの液滴のスラリーを生産するためには、1本の流路から10μL/分以上の液滴をスラリーとして排出する能力が必要となる。   In general, as an actual production amount, it is conceivable that about 10,000 L of liquid droplets are obtained as a slurry per year (hereinafter, the present invention has a capacity to produce a slurry containing 10,000 L of liquid droplets per year. It will be defined as mass production.) Further, as a feature of the microreactor, a concept of numbering up is proposed in which the production capacity per unit time of droplets can be improved by increasing the number of the same flow paths. However, there are almost no reports of actually numbering up the microreactor for mass production other than the example carried out by the present inventors (for example, see Non-Patent Document 1). As shown in Non-Patent Document 1, for example, when the micro-channels are arranged radially on a micro-channel substrate having a diameter of 130 mm, about 10 to 100 are used, and when the substrates are stacked, 5 to 10 are also used. Even if the stacked microreactors are installed in parallel, the parallel performance of about 5 to 10 is the current result, and the maximum number of flow paths is about 10,000 at the present time. Can be assumed. Using the above-described mass production system using a microreactor, it is assumed that the actual operating days are 210 days and the liquid is sent for 8 hours a day. The ability to discharge droplets of 10 μL / min or more as a slurry is required.

従って平均粒径約60μm程度の液滴を生成する場合の送液速度は385μL/分未満であるため、十分に上記量産条件を満たすことがわかる。   Accordingly, it can be seen that the liquid feed speed when producing droplets having an average particle size of about 60 μm is less than 385 μL / min, and thus sufficiently satisfies the above-mentioned mass production condition.

一方、平均粒径約4μm程度の液滴を生成する場合を考える。この場合、流路Cの体積は、内径Rが5μm、流路長Lが5μmの円筒状の体積に相当する。ガラス流路に対して水を流路Cに送り込む条件は(式6)を満たす必要があるから、線速度vは、3.275m/s未満である必要があり、(式7)からこのときの送液速度uは3.86μL/分未満である必要がある。前述したマイクロリアクターによる大量生産システムで年間1万Lの液滴のスラリーを生産するには、10μL/分以上の送液速度が必要であるため、この条件では想定目標の1/3未満しか生産できないことがわかる。実際、特許文献2の例では液滴を生成する原料を連続的に流す態様ではなく、液滴の原料となる液体を流したあと、液体を流路Cのみに蓄えるために流路Aから液滴の原料となる液体を排除し、さらに流路Cに蓄えられた液体を流路Bに排出するために流路Aに流体を送液する手段を伴っており、実質的には3.86μL/分の数分の1〜数十分の1の送液速度となり、想定目標の1/10〜1/30程度以下の生産能力となる。従って、特許文献2の方法では、平均粒径が数μm程度で分散度が10%未満の液滴を生成することが可能ではあるが、その生成速度が遅いために、実用的な工業的規模に相当する年間1万Lの生産に適用することは非常に困難であった。   On the other hand, let us consider a case where droplets having an average particle diameter of about 4 μm are generated. In this case, the volume of the flow path C corresponds to a cylindrical volume having an inner diameter R of 5 μm and a flow path length L of 5 μm. Since the condition for feeding water into the channel C with respect to the glass channel needs to satisfy (Equation 6), the linear velocity v needs to be less than 3.275 m / s. The liquid feed rate u of the liquid crystal must be less than 3.86 μL / min. In order to produce a slurry of 10,000 liters of droplets annually with the above-described mass production system using a microreactor, a liquid feed speed of 10 μL / min or more is required. I understand that I can't. Actually, in the example of Patent Document 2, the material for generating the droplets is not continuously flowed, but the liquid from the flow path A is stored in order to store the liquid only in the flow path C after flowing the liquid as the raw material of the droplets. This is accompanied by a means for sending a fluid to the channel A in order to eliminate the liquid as a raw material of the droplets and discharge the liquid stored in the channel C to the channel B, and is substantially 3.86 μL. The liquid feeding speed is 1 to several tens of minutes per minute, and the production capacity is about 1/10 to 1/30 or less of the assumed target. Therefore, in the method of Patent Document 2, it is possible to generate droplets having an average particle size of about several μm and a degree of dispersion of less than 10%, but since the generation speed is slow, a practical industrial scale is required. It was very difficult to apply to the production of 10,000 L per year.

国際公開WO02/068104パンフレットInternational Publication WO02 / 068104 Pamphlet

特開2002−357616JP 2002-357616 A A.Kawai、T.Futamiら著、「MASS−PRODUCTION SYSTEM OF NEARLY MONODISPERSE DIAMETER GELPARTICLES USING DROPLETS FORMATION IN A MICROCHANNEL」, Proceedings of the μ−TAS 2002 Symposium,2002年発行,368−370頁A. Kawai, T .; Futami et al., “MASS-PRODUCTION SYSTEM OF NEARLY MONODISPERSE DIAMETER GELPARTICLES USING DROPLESS FORMATION IN A MICROCHANNEL, page 2

以上のように前述したように流体のせん断力や毛細管現象により微小液滴を生成する従来の技術では、平均粒径が10μm未満であり、かつ粒径分散度が10%未満の均一粒径の液滴を大量に生成することは非常に困難であった。   As described above, in the conventional technique for generating micro droplets by the shearing force of the fluid or the capillary phenomenon as described above, the average particle size is less than 10 μm and the particle size dispersion degree is less than 10%. It was very difficult to produce a large amount of droplets.

本発明は、上記課題鑑みてなされたもので、微小流路内で平均粒径が10μm未満であり、さらに粒径分散度が10%未満の均一粒径の微小液滴を、工業的規模となる大量に生成することを可能とする微小流路構造体及びそれを用いた液滴生成方法を提供することにある。   The present invention has been made in view of the above-mentioned problems. Microdroplets having a uniform particle size having an average particle size of less than 10 μm and a particle size dispersion of less than 10% in a microchannel are regarded as an industrial scale. An object of the present invention is to provide a microchannel structure that can be generated in a large amount and a droplet generation method using the same.

本発明は、上記課題を解決する手段として、少なくとも一つの基板上に形成された第1の流路、第2の流路及び第3の流路を有する微小流路構造体であって、第1の流路は第1の流体導入口及び第1の流体排出口と連通しており、第2の流路は第2の流体導入口及び第2の流体排出口と連通しており、第3の流路は前記第1の流路と前記第2の流路と連通すると共に、第3の流路内の第2の流路側において流路が1以上の仕切り壁で分割されている微小流路構造体を用い、前記第1の流路に導入された液体が、前記第1の流路の流路壁において開口する前記第3の流路の開口部を介して前記第3の流路内に送り込み、前記液体を送りこんだ後、前記第1の流路に残留する前記液体を取り除き、前記第3の流路の容積に応じた体積の液体を蓄え、前記蓄えた液体を前記仕切り壁を通過させることにより分割して液滴を生成し、前記第2の流路に前記液滴を送り出すことによる液滴生成方法を提供することで、上記の従来技術による課題を解決することができ、遂に本発明を完成することができた。以下、本発明を詳細に説明する。   The present invention provides a microchannel structure having a first channel, a second channel, and a third channel formed on at least one substrate as means for solving the above-described problems, The first channel is in communication with the first fluid inlet and the first fluid outlet, the second channel is in communication with the second fluid inlet and the second fluid outlet, The third flow path communicates with the first flow path and the second flow path, and the flow path is divided by one or more partition walls on the second flow path side in the third flow path. Using the flow channel structure, the liquid introduced into the first flow channel passes through the opening of the third flow channel that opens in the flow channel wall of the first flow channel. After the liquid is fed into the passage, the liquid remaining in the first flow path is removed, and a volume of liquid corresponding to the volume of the third flow path is stored. By providing a droplet generation method by dividing the stored liquid by passing through the partition wall to generate droplets and sending the droplets to the second flow path, the above-described conventional technology The present invention has finally been completed. Hereinafter, the present invention will be described in detail.

本発明の微小流路構造体は、少なくとも一つの基板上に形成された第1の流路、第2の流路及び第3の流路を有する微小流路構造体であって、第1の流路は第1の流体導入口及び第1の流体排出口と連通しており、第2の流路は第2の流体導入口及び第2の流体排出口と連通しており、第3の流路は前記第1の流路と前記第2の流路と連通すると共に、第3の流路内の第2の流路側において流路が1以上の仕切り壁で分割されている微小流路構造体である。   A microchannel structure according to the present invention is a microchannel structure including a first channel, a second channel, and a third channel formed on at least one substrate, The channel is in communication with the first fluid inlet and the first fluid outlet, the second channel is in communication with the second fluid inlet and the second fluid outlet, A flow path communicates with the first flow path and the second flow path, and the flow path is divided by one or more partition walls on the second flow path side in the third flow path. It is a structure.

前記仕切り壁の幅は特に制限はないが、前記第3の流路において導入される液体等の流体を2以上分割でき、一般的なフォトリソグラフィーとドライエッチングあるいはウェットエッチングで加工できる程度の幅が好ましい。さらには仕切り壁の幅は仕切り壁と仕切り壁の間隔よりも大きい方がより好ましい。これは、仕切り壁と仕切り壁の間から出てきた隣の液滴同士が合一することなく第2の流路に速やかに排出させるためである。また、前記仕切り壁の長さには特に制限は無いが、前記第3の流路の前記第1の流路の連通部から前記第2の流路の連通部まで連続していていることが第3の流路に蓄えた液体を確実に分割することができるのでより好ましい。また、仕切り壁の高さも特に制限はないが、流路C内の液体を確実に分割するためには、流路の深さと同じ高さであることが好ましい。   The width of the partition wall is not particularly limited, but can be divided into two or more fluids such as a liquid introduced in the third flow path, and can be processed by general photolithography and dry etching or wet etching. preferable. Furthermore, the width of the partition wall is more preferably larger than the interval between the partition wall and the partition wall. This is because the adjacent droplets coming out between the partition walls and the partition walls are quickly discharged to the second flow path without being united. Further, the length of the partition wall is not particularly limited, but the partition wall is continuous from the communication portion of the first flow channel to the communication portion of the second flow channel. This is more preferable because the liquid stored in the third flow path can be reliably divided. The height of the partition wall is not particularly limited, but is preferably the same height as the depth of the flow path in order to reliably divide the liquid in the flow path C.

本発明の液滴生成方法は、前述した微小流路構造体を用いて、前記第1の流路に液体を導入し、前記第1の流路の流路壁において開口する前記第3の流路の開口部を介して前記第3の流路内に液体を送りこみ、前記液体を送りこんだ後、前記第1の流路に残留する前記液体を取り除き、前記第3の流路の容積に応じた体積の液体を蓄え、前記蓄えた液体を前記仕切り壁を通過させることにより分割して液滴を生成し前記第2の流路に前記液滴を送り出す液滴生成方法である。このようにすることで、流路Cの実質的体積をV[m]とし、仕切り壁で区切られた数をNとすると、V/N[m]の体積の液滴がN個同時に生成可能となる。当然仕切り壁の数が多いほど平均粒径の小さい液滴が大量に生成される。 The droplet generation method of the present invention uses the above-described microchannel structure to introduce a liquid into the first channel, and the third flow opening at the channel wall of the first channel. A liquid is fed into the third flow path through the opening of the path, and after the liquid is fed, the liquid remaining in the first flow path is removed, and the volume of the third flow path is reduced. In this droplet generation method, a liquid having a corresponding volume is stored, the stored liquid is divided by passing through the partition wall to generate a droplet, and the droplet is sent to the second flow path. In this way, assuming that the substantial volume of the channel C is V [m 3 ] and the number divided by the partition walls is N, N droplets having a volume of V / N [m 3 ] are simultaneously obtained. Can be generated. Naturally, the larger the number of partition walls, the larger the number of droplets having a smaller average particle diameter.

また本発明の微小流路構造体は、前記第3の流路の仕切り壁により分割された1分割分の実質的容量が0.5[pL]未満になるように前記第3の流路を仕切り壁により、複数かつ均等に分割することにより、平均粒径が10μm未満であり、かつ粒径分散度が10%未満の非常に均一な微小液滴を生成することが可能となる。   In the microchannel structure according to the present invention, the third channel is arranged so that the substantial capacity of one division divided by the partition wall of the third channel is less than 0.5 [pL]. By dividing into a plurality of and evenly by the partition wall, it becomes possible to generate very uniform micro droplets having an average particle size of less than 10 μm and a particle size dispersion of less than 10%.

例えば、第3の流路を幅100μm、深さ1μm、長さ50μmとし、仕切り壁は流路Cの流路B側の開口部近傍において、長さ1μ、仕切り壁の幅5μm、仕切り壁と仕切り壁の間隔5μmとして、流路Cの幅方向に10等分した仕切り壁を形成する。この場合、流路Cの体積は約5[pL]であり、この体積を10等分に分割した平均粒径9.8μm液滴を10個生成することができる。また、フォトリソグラフィーとドライエッチングあるいはウェットエッチングによる流路の製作精度は、一般に±5μm以内であるので、10%未満の粒径分散度である均一な粒径の液滴を生成することができる。   For example, the third channel has a width of 100 μm, a depth of 1 μm, and a length of 50 μm, and the partition wall has a length of 1 μm, a partition wall width of 5 μm, and a partition wall in the vicinity of the opening on the channel B side of the channel C. A partition wall divided into 10 equal parts in the width direction of the flow path C is formed with an interval of 5 μm between the partition walls. In this case, the volume of the flow path C is about 5 [pL], and ten droplets having an average particle diameter of 9.8 μm obtained by dividing the volume into 10 equal parts can be generated. In addition, since the flow path manufacturing accuracy by photolithography and dry etching or wet etching is generally within ± 5 μm, it is possible to generate droplets having a uniform particle size with a particle size dispersion of less than 10%.

なお、ここで述べる流路とは、特に断りが無い限り微小流路を意味している。一般的に微小流路とは、流路の幅が1μm〜500μm、好ましくは5μm〜200μmであり、流路の深さは0.1μm〜200μm、好ましくは1μm〜50μmであり、流路の長さは、1μm〜50cm、好ましくは10μm〜5cmの流路を意味する。しかしながら、本発明における流路は、上記大きさの微小流路であってもよいが、特に上記範囲になければいけないということでもない。   The flow path described here means a micro flow path unless otherwise specified. In general, a microchannel has a channel width of 1 μm to 500 μm, preferably 5 μm to 200 μm, a channel depth of 0.1 μm to 200 μm, preferably 1 μm to 50 μm, and the length of the channel. The thickness means a flow path of 1 μm to 50 cm, preferably 10 μm to 5 cm. However, the flow channel in the present invention may be a micro flow channel of the above size, but it does not have to be in the above range.

また本発明の微小流路構造体は、前記第1の流路と前記第2の流路の流路壁の親媒性が、前記第3の流路の流路の流路壁との親媒性と異なる微小流路構造体である。   In the microchannel structure of the present invention, the lyophilicity of the channel walls of the first channel and the second channel is close to the channel wall of the channel of the third channel. It is a micro flow channel structure different from the medium.

例えば、前記第1の流路と前記第2の流路の流路壁を疎水性とし、前記第3の流路の流路壁を親水性とすることにより、親水性の液滴を第3の流路に滞留させ、親水性の液滴を生成することがより容易になる。また逆に前記第1の流路と前記第2の流路の流路壁を親水性とし、前記第3の流路の流路壁を疎水性とすることにより、親水性の液滴を第3の流路に滞留させ、疎水性の液滴を生成することがより容易になる。   For example, the flow path walls of the first flow path and the second flow path are made hydrophobic, and the flow path wall of the third flow path is made hydrophilic, so that the hydrophilic liquid droplets are made third. It is easier to generate hydrophilic droplets by staying in the channel. Conversely, the flow path walls of the first flow path and the second flow path are made hydrophilic, and the flow path wall of the third flow path is made hydrophobic, so that the hydrophilic liquid droplets are formed in the first flow path. It becomes easier to generate hydrophobic droplets by staying in the three flow paths.

また本発明の液滴生成方法は、前記第3の流路の蓄えた液体を、前記仕切り壁を通過させることにより分割して液滴を生成し前記第2の流路に前記液滴を送り出す手段が、前記第1の流路に残留する前記液体を取り除くために前記第1の流路に送りこまれた流体の圧力による液滴生成方法である。このようにすることで、液滴の原料となる液体とそれを排除する流体を交互に送り込むことで、連続して液滴を生成することが可能となる。   Further, in the droplet generation method of the present invention, the liquid stored in the third channel is divided by passing through the partition wall to generate a droplet, and the droplet is sent out to the second channel. The means is a droplet generation method by the pressure of the fluid fed into the first flow path in order to remove the liquid remaining in the first flow path. By doing in this way, it becomes possible to produce | generate a droplet continuously by sending alternately the liquid used as the raw material of a droplet, and the fluid which excludes it.

ここで、液滴の原料となる液体を排除する流体が気体の場合は液滴と同時に気泡が流路Bに発生し、この気泡の影響で流路Bに排出された液滴が合一したり分割することで均一な粒径を維持することができなくなるため、液体であることがより好ましい。また、液滴の原料となる液体を排除する流体は、液体であれば特に制限はないが、排除用の液体自体が液滴とならないように前記第2の流路に送液している液体と同じ液体であることがより好ましい。   Here, when the fluid that excludes the liquid that is the raw material of the liquid droplet is a gas, bubbles are generated in the flow path B simultaneously with the liquid droplet, and the liquid droplets discharged into the flow path B are united by the influence of the air bubbles. It is more preferable to use a liquid because it is impossible to maintain a uniform particle size by dividing the film. The fluid that excludes the liquid that is the raw material of the droplet is not particularly limited as long as it is a liquid, but the liquid that is fed to the second flow path so that the exclusion liquid itself does not become a droplet. It is more preferable that the same liquid.

また本発明の微小流路構造体は、前記第3の流路の前記仕切り壁で区切られた部分の各々の容積が、実質的に等しいことを特徴とする微小流路構造体であり、このようにすることで、仕切り壁で分割した液滴の体積を正確に規定することが可能となり、平均粒径の分散度が10%未満の非常に均一な粒径の液滴を生成することが可能となる。ここで、各々の容積が実質的に等しいとは、各々の容積の差が±5%未満であることを意味する。   The microchannel structure according to the present invention is a microchannel structure characterized in that the volumes of the portions of the third channel partitioned by the partition wall are substantially equal. By doing so, it becomes possible to accurately define the volume of the liquid droplets divided by the partition wall, and it is possible to generate liquid droplets having a very uniform particle size with an average particle size dispersion of less than 10%. It becomes possible. Here, that each volume is substantially equal means that the difference of each volume is less than +/- 5%.

また本発明の微小流路構造体は、前述した第1の流路と第2の流路と第3の流路を1組とした流路が平面的あるいは立体的に複数存在する微小流路構造体であり、また、前記第1の流路と前記第2の流路がすべて連通しており、前記第1の流路に連通した前記第1の流体導入口及び前記第1の流体排出口と、前記第2の流路に連通した前記第2の流体導入口及び前記第2の流体排出口が各々1つずつ備えられていても良い。このようにすることで、大量の液滴を生成することが可能となる。以下では図を用いてさらに本発明を詳細に説明する。   In addition, the microchannel structure according to the present invention includes a microchannel in which a plurality of channels including the first channel, the second channel, and the third channel described above are present in a planar or three-dimensional manner. The first flow path and the second flow path are all in communication, and the first fluid introduction port and the first fluid exhaust connected to the first flow path. Each of the outlet, the second fluid inlet and the second fluid outlet connected to the second flow path may be provided. By doing so, it becomes possible to generate a large amount of droplets. Hereinafter, the present invention will be described in more detail with reference to the drawings.

図4には本発明の微小流路構造を説明するための概念図が示されており、図5〜図8は図4の所定の個所の断面図が示されている。また、図9〜図12には本発明の原理を説明する概念図が示されている。なお、この例では流路の内壁は親水性であり、親水性の液滴、例えば水の液滴を生成する場合を想定している。   FIG. 4 is a conceptual diagram for explaining the microchannel structure of the present invention, and FIGS. 5 to 8 are sectional views of predetermined portions of FIG. 9 to 12 are conceptual diagrams for explaining the principle of the present invention. In this example, it is assumed that the inner wall of the flow path is hydrophilic and a hydrophilic droplet, for example, a droplet of water is generated.

図9〜図12に示すように、第1の流路として流路A(9)、第2の流路として流路B(10)、第3の流路として流路C(11)の3本の流路が、2本の流路A、流路Bの間に流路Cを橋渡しするような構造を有している。流路Cが流路Aと流路Bとを連結しており、流路Cの流路B側の開口部B(15)には、仕切り壁(16)が備えられている。なおこの場合、流路Cの流路A側の開口部A(14)の断面積は流路Aの開口部A近傍の断面積よりも小さいことが好ましい。   As shown in FIG. 9 to FIG. 12, the flow path A (9) as the first flow path, the flow path B (10) as the second flow path, and the flow path C (11) as the third flow path. The two channels have a structure in which the channel C is bridged between the two channels A and B. The channel C connects the channel A and the channel B, and the opening B (15) on the channel B side of the channel C is provided with a partition wall (16). In this case, the cross-sectional area of the opening A (14) on the flow path A side of the flow path C is preferably smaller than the cross-sectional area in the vicinity of the opening A of the flow path A.

このようにすることで、流路Cの毛管引力が流路Aの毛管引力よりも大きいため、液体Aが流路Aから流路Cに入りこみやすくなり、逆に流路Cから流路Aに出にくくなる。また、一般的に平均粒径が10μm未満の液滴を生成する場合は、仕切り壁と仕切り壁の間隔により形成される断面積は、流路Bの断面積よりも小さいため、開口部Bでの端面における流路Cの毛管引力が流路Bの毛管引力よりも大きいため、流路C内に入り込んだ液体Aは、流路B内に入り込むことはない。   By doing in this way, since the capillary attractive force of the flow path C is larger than the capillary attractive force of the flow path A, the liquid A easily enters the flow path C from the flow path A, and conversely from the flow path C to the flow path A. It becomes difficult to come out. In general, when a droplet having an average particle size of less than 10 μm is generated, the cross-sectional area formed by the interval between the partition wall and the partition wall is smaller than the cross-sectional area of the flow path B. Since the capillary attraction force of the flow path C at the end face is larger than the capillary attraction force of the flow path B, the liquid A that has entered the flow path C does not enter the flow path B.

そして図10に示すように、流路A内に残留する液体Aを、例えば、流路Aに別の液体B(26)を適切な送液圧で送液し、液体Aを流路A内から取り除く。液体Bが適切な送液圧であれば、図11に示すように流路C内の液体Aは、流路C内に留まる。その結果、流路C内の液体Aの両端面たる端面A(25)と端面B(26)とが、流路Cの開口部A(14)ならびに開口部B(15)に位置するようになり、3本の流路A、流路B、流路Cのうちの流路C内のみに液体が瞬間的に残留する。その後、適切な送液圧で液体Bを流路Aに送液することにより、図12に示すように流路Cに蓄えた液体Aを仕切り壁(16)を通過させ実質的に等しい体積に分割することにより液滴(27)を生成し流路Bに液滴を送り出す。   Then, as shown in FIG. 10, for example, the liquid A remaining in the flow path A is supplied to the flow path A with another liquid B (26) at an appropriate liquid supply pressure, and the liquid A is supplied to the flow path A. Remove from. If the liquid B has an appropriate liquid feeding pressure, the liquid A in the channel C remains in the channel C as shown in FIG. As a result, the end face A (25) and the end face B (26), which are both end faces of the liquid A in the channel C, are positioned at the opening A (14) and the opening B (15) of the channel C. Thus, the liquid instantaneously remains only in the channel C among the three channels A, B, and C. Thereafter, the liquid B is fed to the flow path A with an appropriate liquid feed pressure, so that the liquid A stored in the flow path C passes through the partition wall (16) as shown in FIG. By dividing, a droplet (27) is generated, and the droplet is sent out to the channel B.

また、本発明は流路A及び流路Bの親媒性と流路Cの親媒性とが互いに異なるように構成することがさらに好ましい。   Further, it is more preferable that the present invention is configured such that the philicity of the flow path A and the flow path B is different from that of the flow path C.

流路Cの内壁のみを親水性にする場合は、微小流路基板をガラスなどの親水性の材料で微小流路基板を作製し、流路A及び流路Bにシランカップリング剤をトルエン等に溶解させた疎水化溶液を送液すれば良い。この場合、疎水化溶液に対しては、流路Aの断面積よりも流路Cの流路A側の開口部の断面積を小さくし、流路Bの断面積よりも流路Cの流路B側の開口部近傍に備えられた仕切り壁の断面積を除いた部分の断面積が小さいため、流路Cには負の毛細管現象が流路A、流路Bよりもより大きく働くので流路Cに疎水化溶液が入り込むことは無い。このようにすることで、流路A及び流路Bの内壁を疎水性にし、流路Cの内壁を親水性にすることが可能となる。   When only the inner wall of the channel C is made hydrophilic, the micro channel substrate is made of a hydrophilic material such as glass, and the silane coupling agent is added to the channel A and the channel B with toluene or the like. What is necessary is just to send the hydrophobization solution melt | dissolved in (3). In this case, for the hydrophobized solution, the cross-sectional area of the opening on the flow path A side of the flow path C is smaller than the cross-sectional area of the flow path A, and the flow path of the flow path C is smaller than the cross-sectional area of the flow path B. Since the cross-sectional area of the portion excluding the cross-sectional area of the partition wall provided near the opening on the side of the path B is small, the negative capillary action acts on the flow path C more than the flow paths A and B. The hydrophobic solution does not enter the flow path C. By doing in this way, it becomes possible to make the inner wall of the flow path A and the flow path B hydrophobic, and to make the inner wall of the flow path C hydrophilic.

また、また流路Cの内壁のみを疎水性にする場合は、微小流路基板を耐溶剤性が比較的高いポリエーテルイミドやポリアセタール、ナイロン等の疎水性の樹脂で微小流路基板を作製し、流路A及び流路Bに無電解メッキ溶液を送液しPdやNiなどの金属で内壁を修飾すれば良い。この場合、無電解メッキ溶液に対しては、流路Aの断面積よりも流路Cの流路A側の開口部の断面積を小さくし、流路Bの断面積よりも流路Cの流路B側の開口部近傍に備えられた仕切り壁の断面積を除いた部分の断面積が小さいため、流路Cには負の毛細管現象が流路A、流路Bよりもより大きく働くので流路Cに無電解メッキ溶液が入り込むことは無い。このようにすることで、流路A及び流路Bの内壁を親水性にし、流路Cの内壁を疎水性にすることが可能となる。   When only the inner wall of the channel C is made hydrophobic, the micro channel substrate is made of a hydrophobic resin such as polyetherimide, polyacetal, nylon, etc., which has a relatively high solvent resistance. The electroless plating solution may be sent to the flow path A and the flow path B, and the inner wall may be modified with a metal such as Pd or Ni. In this case, for the electroless plating solution, the cross-sectional area of the opening on the flow path A side of the flow path C is made smaller than the cross-sectional area of the flow path A, and the cross-sectional area of the flow path C is smaller than the cross-sectional area of the flow path B. Since the cross-sectional area of the portion excluding the cross-sectional area of the partition wall provided in the vicinity of the opening on the flow channel B side is small, the negative capillary action acts on the flow channel C more than the flow channels A and B. Therefore, the electroless plating solution does not enter the flow path C. By doing in this way, it becomes possible to make the inner wall of the flow path A and the flow path B hydrophilic, and to make the inner wall of the flow path C hydrophobic.

なお、本発明では流路A、流路Bの親媒性と流路Cの親媒性を異ならせる方法は上記方法に限定されるものではない。   In the present invention, the method for differentiating the lyophilicity of the channel A and the channel B from that of the channel C is not limited to the above method.

以上のように、微小流路構造体を構成している微小流路を有する微小流路基板は、例えばガラスや石英、セラミック、シリコン、あるいは金属や樹脂等の基板材料を、機械加工やレーザー加工、エッチングなどにより直接加工することによって製作できる。また、基板材料がセラミックや樹脂の場合は、流路形状を有する金属等の鋳型を用いて成形することで製作することもできる。なお一般的に、前記微小流路基板は、流体導入口、流体排出口、および各微小流路の排出口に対応する位置に直径数mm程度の小穴を設けたカバー体と積層一体化させた微小流路構造体として使用する。カバー体と微小流路基板の接合方法としては、基板材料がセラミックスや金属の場合は、ハンダ付けや接着剤を用いたり、基板材料がガラスや石英、樹脂の場合は、百度〜千数百度の高温下で荷重をかけて熱接合させたり、基板材料がシリコンの場合は洗浄により表面を活性化させて常温で接合させるなどそれぞれの基板材料に適した接合方法が用いられる。   As described above, the micro-channel substrate having the micro-channels constituting the micro-channel structure is formed by machining or laser processing a substrate material such as glass, quartz, ceramic, silicon, or metal or resin. It can be manufactured by direct processing by etching or the like. Further, when the substrate material is ceramic or resin, it can also be manufactured by molding using a mold such as a metal having a channel shape. Generally, the microchannel substrate is laminated and integrated with a cover body having a small hole with a diameter of about several millimeters at a position corresponding to the fluid inlet, the fluid outlet, and the outlet of each microchannel. Used as a microchannel structure. As a method for joining the cover body and the micro-channel substrate, when the substrate material is ceramics or metal, soldering or adhesive is used, or when the substrate material is glass, quartz, or resin, it is a hundred to several hundreds of degrees A bonding method suitable for each substrate material is used, such as thermal bonding by applying a load at a high temperature, or when the substrate material is silicon, by activating the surface by washing and bonding at room temperature.

本発明の微小流路構造体は、少なくとも一つの基板上に形成された第1の流路、第2の流路及び第3の流路を有する微小流路構造体であって、第1の流路は第1の流体導入口及び第1の流体排出口と連通しており、第2の流路は第2の流体導入口及び第2の流体排出口と連通しており、第3の流路は前記第1の流路と前記第2の流路と連通すると共に、第3の流路内の第2の流路側において流路が1以上の仕切り壁で分割されており、この構造体を利用した本発明の液滴生成方法は、第1の流路に液体を導入し、第1の流路の流路壁において開口する第3の流路の開口部を介して第3の流路内に液体を送りこみ、液体を送りこんだ後、第1の流路に残留する液体を取り除き、第3の流路の容積に応じた体積の液体を蓄え、蓄えた液体を仕切り壁を通過させることにより分割して液滴を生成し第2の流路に液滴を送り出す方法である。このような微小流路構造体とそれを用いた液滴生成方法により、平均粒径10μm未満の粒径分散度が10%未満の均一な液滴を大量に生成することが可能となる。 A microchannel structure according to the present invention is a microchannel structure including a first channel, a second channel, and a third channel formed on at least one substrate, The channel is in communication with the first fluid inlet and the first fluid outlet, the second channel is in communication with the second fluid inlet and the second fluid outlet, The flow path communicates with the first flow path and the second flow path, and the flow path is divided by one or more partition walls on the second flow path side in the third flow path. In the droplet generation method of the present invention using the body, the liquid is introduced into the first channel, and the third channel is opened via the opening of the third channel that opens at the channel wall of the first channel. After the liquid is fed into the flow path, the liquid remaining in the first flow path is removed, the volume of liquid corresponding to the volume of the third flow path is stored, and the stored liquid is partitioned A method for feeding the liquid droplets to the second flow path to produce droplets by dividing by passing. With such a microchannel structure and a droplet generation method using the same, it is possible to generate a large amount of uniform droplets having an average particle size of less than 10 μm and a particle size dispersion of less than 10%.

また本発明の微小流路構造体は、第3の流路の仕切り壁により分割された1分割分の実質的容量が0.5[pL]未満である微小流路構造体であり、第3の流路に備えられた仕切り壁で第3の流路の体積に蓄えられた液体を0.5[pL]未満の体積に複数かつ均等に分割することで平均粒径が10μm未満であり、かつ粒径分散度が10%未満の非常に均一な微小液滴を大量に生成することが可能となる。   The microchannel structure according to the present invention is a microchannel structure in which the substantial capacity of one division divided by the partition wall of the third channel is less than 0.5 [pL]. The average particle size is less than 10 μm by dividing the liquid stored in the volume of the third flow path into a volume of less than 0.5 [pL] in a plurality of and evenly divided by the partition wall provided in the flow path of In addition, it is possible to produce a large amount of very uniform fine droplets having a particle size dispersion of less than 10%.

また本発明の液滴生成方法は、第1の流路に導入された液体を、第1の流路の流路壁において開口する第3の流路の開口部を介して第3の流路内に適切な送液圧により送り込み、一時的に第3の流路に液体を蓄え、第1の流路に別の液体を適切な送液圧により送液し、その送液圧により第3の流路の蓄えた液体を前記仕切り壁を通過させることにより分割して液滴を生成し第2の流路に液滴を送り出す液滴生成方法である。このようにすることで、液滴の原料となる液体とそれを排除する流体を交互に送り込み、連続して液滴を生成することが可能となる。   Further, in the droplet generation method of the present invention, the liquid introduced into the first channel passes through the third channel through the opening of the third channel that opens in the channel wall of the first channel. The liquid is fed into the inside of the first flow path, the liquid is temporarily stored in the third flow path, and another liquid is fed into the first flow path with the proper liquid feed pressure. This is a droplet generation method in which the liquid stored in the channel is divided by passing through the partition wall to generate droplets and send the droplets to the second channel. By doing so, it becomes possible to alternately generate the liquid that is the raw material of the liquid droplets and the fluid that eliminates the liquid, and continuously generate the liquid droplets.

また、第1の流路及び第2の流路の流路壁を親水性とし、第3の流路の流路壁を疎水性とすることにより、疎水性の液滴を第3の流路に滞留させ、疎水性の液滴を生成することがより容易になる。また逆に第1の流路及び第2の流路の流路壁を疎水性とし、前記第3の流路の流路壁を親水性とすることにより、親水性の液滴を第3の流路に滞留させ、親水性の液滴を生成することがより容易になる。   Further, by making the flow path walls of the first flow path and the second flow path hydrophilic and making the flow path wall of the third flow path hydrophobic, the hydrophobic liquid droplets are transferred to the third flow path. And it becomes easier to produce hydrophobic droplets. Conversely, the flow path walls of the first flow path and the second flow path are made hydrophobic, and the flow path wall of the third flow path is made hydrophilic so that the hydrophilic liquid droplets are transferred to the third flow path. It becomes easier to generate hydrophilic droplets by staying in the flow path.

また本発明の微小流路構造体は、第3の流路内の仕切り壁で区切られた部分の容積の各々が、実質的に等しい。このようにすることで、仕切り壁で分割した液滴の体積を正確に規定することが可能となり、平均粒径の分散度が10%未満の非常に均一な粒径の液滴を生成することが可能となる。   Further, in the microchannel structure according to the present invention, the volumes of the portions separated by the partition walls in the third channel are substantially equal. By doing so, it becomes possible to accurately define the volume of the droplets divided by the partition wall, and to generate droplets with a very uniform particle size with an average particle size dispersion of less than 10%. Is possible.

また本発明の微小流路構造体は、前述した第1の流路と第2の流路と第3の流路を1組とした流路が平面的あるいは立体的に複数存在する微小流路構造体であり、また、第1の流路と第2の流路がすべて連通しており、第1の流路に連通した第1の流体導入口及び第1の流体排出口と、第2の流路に連通した第2の流体導入口及び第2の流体排出口が各々1つずつ備えられていても良い。このようにすることで、大量の液滴を生成することが可能となる。   In addition, the microchannel structure according to the present invention includes a microchannel in which a plurality of channels including the first channel, the second channel, and the third channel described above are present in a planar or three-dimensional manner. The first flow path and the second flow path are all in communication with each other, the first fluid introduction port and the first fluid discharge port communicating with the first flow path, and the second flow path. Each of the second fluid inlet and the second fluid outlet connected to the flow path may be provided. By doing so, it becomes possible to generate a large amount of droplets.

以下に本発明の実施の形態の一例について説明する。なお本発明は、以下の実施の形態のみに限定されるものではなく、発明の要旨を逸脱しない範囲で、任意に変更が可能であることは言うまでもない。
(実施例)
本発明の実施例における液滴生成用微小流路基板の概略図を図13に示す。微小流路は70mm×20mm×1t(厚さ)のパイレックス(登録商標)ガラス上に、流路A(9)、流路B(10)、及び流路C(11)を形成した。流路Aと流路Bは一般的なフォトリソグラフィーとウエットエッチングにより形成した。流路Aの流路幅は500μm、流路深さは50μm、流路長は3cmである。また、流路Bの流路幅は300μm、流路深さは50μm、流路長は3cmである。流路Cは、流路Aと連通する開口部の幅が100μm、流路Bと連通する開口部の幅が500μm、長さは50μm、深さを1μmとした。また、図14は、図13のF部の一部分を拡大した図である。図14に示すように流路Bと連通する開口部近傍に幅5.2μm、長さ10μmの仕切り壁(16)を4.8μm間隔で開口部方向に等間隔に49個備えた。以上の流路形状から、この実施例の場合の流路Cの実質的容量は約15pLである。
An example of the embodiment of the present invention will be described below. Needless to say, the present invention is not limited to the following embodiments, and can be arbitrarily changed without departing from the gist of the invention.
(Example)
FIG. 13 shows a schematic diagram of a micro-channel substrate for generating droplets in an example of the present invention. As the microchannel, a channel A (9), a channel B (10), and a channel C (11) were formed on Pyrex (registered trademark) glass of 70 mm × 20 mm × 1 t (thickness). The channel A and the channel B were formed by general photolithography and wet etching. The channel A has a channel width of 500 μm, a channel depth of 50 μm, and a channel length of 3 cm. The channel B has a channel width of 300 μm, a channel depth of 50 μm, and a channel length of 3 cm. In the channel C, the width of the opening communicating with the channel A is 100 μm, the width of the opening communicating with the channel B is 500 μm, the length is 50 μm, and the depth is 1 μm. FIG. 14 is an enlarged view of a part of the F part in FIG. As shown in FIG. 14, 49 partition walls (16) having a width of 5.2 μm and a length of 10 μm were provided in the vicinity of the opening communicating with the flow path B at an equal interval of 4.8 μm in the direction of the opening. From the above flow path shape, the substantial capacity of the flow path C in this embodiment is about 15 pL.

次に図13に示すように流路A用の流体導入口A(28)と流体排出口A(29)、流路B用の流体導入口B(30)と流体排出口B(31)を所定の位置に直径1mmの貫通孔を形成した70mm×20mm×1t(厚さ)のパイレックス(登録商標)ガラスのカバー体(32)を微小流路基板(33)に一般的な熱接合により接合し、図15に示すような微小流路構造体(34)を製作した。   Next, as shown in FIG. 13, the fluid inlet A (28) and the fluid outlet A (29) for the channel A, and the fluid inlet B (30) and the fluid outlet B (31) for the channel B are provided. A 70 mm × 20 mm × 1 t (thickness) Pyrex (registered trademark) glass cover body (32) in which a through hole having a diameter of 1 mm is formed at a predetermined position is bonded to a microchannel substrate (33) by general thermal bonding. And the microchannel structure (34) as shown in FIG. 15 was manufactured.

次に図16に示すように微小流路構造体(34)の流路A用の流体導入口A(28)と流体排出口A(29)、流路B用の流体導入口B(30)と流体排出口B(31)に流体を導入、排出できるように、テフロン(登録商標)製のチューブ(36)を接続した。テフロン(登録商標)製のチューブは外径0.9mm、内径200μm、長さ20cmである。流路A用の流体導入口側のテフロン(登録商標)チューブには、セレクター(37)を設けて、分散相(38)の入ったシリンジポンプA(40)と連続相(39)の入ったシリンジポンプB(41)を接続し、分散相と連続相を交互に切り替えて流せるようにした。流路B用の流体導入口側のテフロン(登録商標)チューブには、連続相(39)の入ったシリンジポンプC(42)を接続した。   Next, as shown in FIG. 16, the fluid inlet A (28) and the fluid outlet A (29) for the channel A of the microchannel structure (34), and the fluid inlet B (30) for the channel B A tube (36) made of Teflon (registered trademark) was connected so that the fluid could be introduced into and discharged from the fluid outlet B (31). A tube made of Teflon (registered trademark) has an outer diameter of 0.9 mm, an inner diameter of 200 μm, and a length of 20 cm. The Teflon (registered trademark) tube on the fluid inlet side for the flow path A is provided with a selector (37), and contains a syringe pump A (40) containing a dispersed phase (38) and a continuous phase (39). A syringe pump B (41) was connected so that the dispersed phase and the continuous phase could be switched alternately. A syringe pump C (42) containing a continuous phase (39) was connected to the Teflon (registered trademark) tube on the fluid inlet side for the channel B.

なお、実際の液滴生成の前に、流路Aと流路Bを以下の手順で疎水処理した。まず、飽和KOHエタノール溶液を0.4mL/時間の送液速度で20分間流し、エタノールで同じ送液速度で15分間洗浄した後、トルエンを同じ送液速度で15分間流した。次にトルエンに体積比10%のオクタデシルトリクロロシランを混ぜた疎水化溶液を送液速度0.4mL/時間で3時間流した。最後にヘキサンを用いて、送液速度0.4mL/時間で15分間流し洗浄した。   In addition, before actual droplet generation, the flow path A and the flow path B were subjected to a hydrophobic treatment by the following procedure. First, a saturated KOH ethanol solution was allowed to flow for 20 minutes at a liquid feed rate of 0.4 mL / hour, washed with ethanol for 15 minutes at the same liquid feed rate, and then toluene was allowed to flow for 15 minutes at the same liquid feed rate. Next, a hydrophobized solution in which 10% by volume of octadecyltrichlorosilane was mixed with toluene was allowed to flow for 3 hours at a feed rate of 0.4 mL / hour. Finally, hexane was used for washing for 15 minutes at a liquid feed rate of 0.4 mL / hour.

実際の液滴を生成する際には、連続相に体積比3%のポリビニルアルコール水溶液を用い,分散相にモノマー(スチレン)、ジビニルベンゼン、酢酸ブチル及び過酸化ベンゾイルの混合溶液を用いた。   When producing actual droplets, an aqueous polyvinyl alcohol solution having a volume ratio of 3% was used for the continuous phase, and a mixed solution of monomer (styrene), divinylbenzene, butyl acetate and benzoyl peroxide was used for the dispersed phase.

図17に示すよう流路B(10)には5μL/分の送液速度で連続相(39)を流しつづけた。流路A(9)にはにまず分散相(38)を5μL/分の送液速度で導入した。分散相は流路Aの流路壁(22)において開口する流路C(11)の開口部A(14)を介して開口部Aから流路C内に導入され、流路Aの断面積よりも流路Cの断面積が小さいことによる流路Cの毛管引力により、流路Cに導入された分散相は、流路Aに逆流することは無かった。また、流路Cの反対側の流路端、即ち、流路Bの流路壁(23)において開口している流路Cの開口部B(15)まで到達した分散相は、流路C内の仕切り壁による毛細管引力によってせき止められ、流路B内に入り込むことはなく流路C内のみに分散相が残留した。   As shown in FIG. 17, the continuous phase (39) was kept flowing at a flow rate of 5 μL / min in the flow path B (10). First, the dispersed phase (38) was introduced into the flow path A (9) at a liquid feed rate of 5 μL / min. The dispersed phase is introduced into the channel C from the opening A via the opening A (14) of the channel C (11) that opens in the channel wall (22) of the channel A, and the cross-sectional area of the channel A The dispersed phase introduced into the channel C did not flow back into the channel A due to the capillary attraction of the channel C due to the smaller cross-sectional area of the channel C. In addition, the dispersed phase that has reached the flow path end on the opposite side of the flow path C, that is, the opening B (15) of the flow path C that opens at the flow path wall (23) of the flow path B It was blocked by capillary attraction by the inner partition wall, and did not enter the flow path B, and the dispersed phase remained only in the flow path C.

そして図18〜図20に示すように、流路Aから連続相(39)を2MPaの送液圧で流すことで流路A内に残留する分散相(38)を取り除くと同時に、流路Cに蓄えた分散相(38)を49個の仕切り壁を通過させ50個に分割することにより液滴(27)を生成し流路B(10)に生成した液滴を送り出し、この操作を10回繰り返した。   Then, as shown in FIGS. 18 to 20, the continuous phase (39) is flowed from the flow path A with a liquid supply pressure of 2 MPa to remove the dispersed phase (38) remaining in the flow path A, and at the same time, the flow path C The dispersed phase (38) stored in the gas is passed through 49 partition walls and divided into 50, thereby generating droplets (27) and delivering the generated droplets to the flow path B (10). Repeated times.

生成された液滴をサンプル瓶(35)で回収し、顕微鏡で100個の液滴を観察したところ、平均粒径が8.9μm、粒径分散度が7.5%の微小液滴を生成することができた。   The generated droplets were collected in a sample bottle (35), and 100 droplets were observed with a microscope. As a result, micro droplets having an average particle size of 8.9 μm and a particle size dispersion of 7.5% were generated. We were able to.

液滴を生成するためのT字型の流路の概念図(平面図)である。It is a conceptual diagram (plan view) of a T-shaped channel for generating droplets. T字型の流路のA−A’断面拡大図である。It is an A-A 'cross-sectional enlarged view of a T-shaped channel. 微小空間の容積に応じた体積の液滴を生成する流路の概念図(平面図)である。It is a conceptual diagram (plan view) of a flow path for generating droplets having a volume corresponding to the volume of a minute space. 本発明の微小流路構造を説明するための概念図(平面図)である。It is a conceptual diagram (plan view) for demonstrating the microchannel structure of this invention. 図4におけるB−B’断面拡大図である。FIG. 5 is an enlarged cross-sectional view along B-B ′ in FIG. 4. 図4におけるC−C’断面拡大図である。It is the C-C 'cross section enlarged view in FIG. 図4におけるD−D’断面拡大図である。It is D-D 'cross-sectional enlarged view in FIG. 図4におけるE−E’断面拡大図である。It is the E-E 'cross section enlarged view in FIG. 本発明の原理を説明する第1の概念図(平面図)である。It is the 1st conceptual diagram (plan view) explaining the principle of the present invention. 本発明の原理を説明する第2の概念図(平面図)である。It is a 2nd conceptual diagram (plan view) explaining the principle of this invention. 本発明の原理を説明する第3の概念図(平面図)である。It is a 3rd conceptual diagram (plan view) explaining the principle of this invention. 本発明の原理を説明する第4の概念図(平面図)である。It is the 4th conceptual diagram (plan view) explaining the principle of this invention. 本発明の実施例における液滴生成用微小流路基板の概略図(斜視図)である。It is the schematic (perspective view) of the microchannel substrate for droplet generation in the Example of this invention. 図13のF部の一部分を拡大した斜視図である。It is the perspective view which expanded a part of F section of Drawing 13. 本発明の実施例における微小流路構造体の概略図(斜視図)である。It is the schematic (perspective view) of the microchannel structure in the Example of this invention. 本発明の実施例における実験形態の概念図(斜視図)である。It is a conceptual diagram (perspective view) of the experiment form in the Example of this invention. 本発明の実施例を説明する第1の概念図(平面図)である。It is the 1st conceptual diagram (plan view) explaining the example of the present invention. 本発明の実施例を説明する第2の概念図(平面図)である。It is a 2nd conceptual diagram (plan view) explaining the Example of this invention. 本発明の実施例を説明する第3の概念図(平面図)である。It is the 3rd conceptual diagram (plan view) explaining the Example of this invention. 本発明の実施例を説明する第4の概念図(平面図)である。It is a 4th conceptual diagram (plan view) explaining the Example of this invention.

符号の説明Explanation of symbols

1: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:交差部
7:排出流路
8:排出口
9:流路A
10:流路B
11:流路C
12:開口部近傍A
13:開口部近傍B
14:開口部A
15:開口部B
16:仕切り壁
17:断面積S1
18:断面積S2
19:断面積S3
20:断面積S4
21:液体A
22:流路Aの流路壁
23:流路Bの流路壁
24:液体B
25:端面A
26:端面B
27:液滴
28:流体導入口A
29:流体排出口A
30:流体導入口B
31:流体排出口B
32:カバー体
33:微小流路基板
34:微小流路構造体
35:サンプル瓶
36:チューブ
37:セレクタ
38:分散相
39:連続相
40:シリンジポンプA
41:シリンジポンプB
42:シリンジポンプC

1: Substrate 2: Continuous phase introduction port 3: Continuous phase introduction channel 4: Dispersed phase introduction port 5: Dispersed phase introduction channel 6: Intersection 7: Discharge channel 8: Discharge port 9: Channel A
10: Channel B
11: Channel C
12: Opening vicinity A
13: Opening vicinity B
14: Opening A
15: Opening B
16: Partition wall 17: Cross-sectional area S1
18: Cross-sectional area S2
19: sectional area S3
20: sectional area S4
21: Liquid A
22: Channel wall 23 of channel A: Channel wall 24 of channel B 24: Liquid B
25: End face A
26: End face B
27: Liquid droplet 28: Fluid inlet A
29: Fluid outlet A
30: Fluid inlet B
31: Fluid outlet B
32: Cover body 33: Microchannel substrate 34: Microchannel structure 35: Sample bottle 36: Tube 37: Selector 38: Dispersed phase 39: Continuous phase 40: Syringe pump A
41: Syringe pump B
42: Syringe pump C

Claims (6)

少なくとも一つの基板上に形成された第1の流路、第2の流路及び第3の流路を有する微小流路構造体であって、第1の流路は第1の流体導入口及び第1の流体排出口と連通しており、第2の流路は第2の流体導入口及び第2の流体排出口と連通しており、第3の流路は前記第1の流路と前記第2の流路と連通しており、前記第1の流路と前記第2の流路の流路壁の親媒性は前記第3の流路の流路壁の親媒性と異なり、第3の流路内の第2の流路側において流路が1以上の仕切り壁で分割されていることを特徴とする微小流路構造体。 A microchannel structure having a first channel, a second channel, and a third channel formed on at least one substrate, wherein the first channel has a first fluid inlet and The second fluid channel communicates with the first fluid outlet, the second fluid channel communicates with the second fluid inlet and the second fluid fluid outlet, and the third fluid channel communicates with the first fluid channel. wherein has the second flow path and communicating, solvophilic of the first flow path and the flow path wall of the second channel is different from solvophilic flow walls of the third channel A microchannel structure characterized in that the channel is divided by one or more partition walls on the second channel side in the third channel. 前記第3の流路の前記仕切り壁で区切られた部分の容積の各々が、実質的に等しいことを特徴とする請求項1に記載の微小流路構造体。 2. The microchannel structure according to claim 1, wherein volumes of portions of the third channel partitioned by the partition wall are substantially equal. 前記第3の流路の仕切り壁により分割された1分割分の液滴の実質的容量が0.5×10−12リットル[pL]未満であることを特徴とする請求項1又は請求項2記載の微小流路構造体。 The substantial volume of the liquid droplet for one division divided by the partition wall of the third flow path is less than 0.5 × 10 −12 liters [pL]. The microchannel structure according to the description. 請求項1〜3記載のいずれかに記載の流路が平面的あるいは立体的に複数存在することを特徴とする微小流路構造体。 A microchannel structure comprising a plurality of channels according to any one of claims 1 to 3 planarly or three-dimensionally. 請求項1〜3記載のいずれかに記載の流路が平面的あるいは立体的に複数存在し、前記第1の流路と前記第2の流路がすべて連通しており、前記第1の流路に連通した前記第1の流体導入口及び前記第1の流体排出口と、前記第2の流路に連通した前記第2の流体導入口及び前記第2の流体排出口が各々1つずつ備えられたことを特徴とする微小流路構造体。 A plurality of the flow paths according to any one of claims 1 to 3 are present in a planar or three-dimensional manner, and the first flow path and the second flow path are all in communication, and the first flow path One each of the first fluid inlet and the first fluid outlet connected to the passage, and the second fluid inlet and the second fluid outlet connected to the second flow path, respectively. A microchannel structure characterized by being provided. 前記第1の流路に導入された液体(第1の液体)が、前記第1の流路の流路壁において開口する前記第3の流路の開口部を介して前記第3の流路内に送りこむ手段を有し、前記第3の流路内に送りこむ手段が、第1の液体の圧力であり、第1の液体を送りこんだ後、前記第1の流路に残留する第1の液体を取り除き、前記第3の流路の容積に応じた体積の第1の液体を蓄え、前記蓄えた第1の液体を前記仕切り壁を通過させることにより分割して液滴を生成し前記第2の流路に前記液滴を送り出す手段を有し、前記第3の流路の蓄えた第1の液体を前記仕切り壁を通過させることにより分割して液滴を生成し前記第2の流路に前記液滴を送り出す手段が、前記第1の流路に残留する第1の液体を取り除くために前記第1の流路に送りこまれた液体(第2の液体)の圧力によることを特徴とし、液滴の原料となる第1の液体と、第1の液体を取り除くための第2の液体を交互に送り込むことで、連続して液滴を生成することを特徴とする請求項1〜5いずれかに記載の微小流路構造体を用いた液滴生成方法。The liquid (first liquid) introduced into the first flow path passes through the opening of the third flow path that opens in the flow path wall of the first flow path, and thus the third flow path And means for feeding into the third flow path is the pressure of the first liquid, and the first liquid remaining in the first flow path after feeding the first liquid. The liquid is removed, the first liquid having a volume corresponding to the volume of the third flow path is stored, and the stored first liquid is divided by passing through the partition wall to generate droplets. Means for delivering the liquid droplets to the second flow path, and the first liquid stored in the third flow path is divided by passing through the partition wall to generate liquid droplets to generate the second flow Means for delivering the droplets to the channel is fed into the first channel to remove the first liquid remaining in the first channel; It is characterized by the pressure of the body (second liquid), and the liquid is continuously fed by alternately feeding the first liquid as the raw material of the droplets and the second liquid for removing the first liquid. A droplet generation method using the microchannel structure according to any one of claims 1 to 5, wherein the droplet is generated.
JP2004118970A 2004-04-14 2004-04-14 Microchannel structure and droplet generation method using the same Expired - Fee Related JP4547967B2 (en)

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JPH0433931U (en) * 1990-07-13 1992-03-19
JPH05179004A (en) * 1991-12-26 1993-07-20 Kobe Steel Ltd Production of uniform droplet group
JP2002357616A (en) * 2001-05-31 2002-12-13 Inst Of Physical & Chemical Res Trace liquid control mechanism
JP2004163104A (en) * 2001-10-18 2004-06-10 Aida Eng Ltd Minute quantity liquid scaling structure and microchip having the same

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0433931U (en) * 1990-07-13 1992-03-19
JPH05179004A (en) * 1991-12-26 1993-07-20 Kobe Steel Ltd Production of uniform droplet group
JP2002357616A (en) * 2001-05-31 2002-12-13 Inst Of Physical & Chemical Res Trace liquid control mechanism
JP2004163104A (en) * 2001-10-18 2004-06-10 Aida Eng Ltd Minute quantity liquid scaling structure and microchip having the same

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