Abstract

Microfluidic devices have achieved rapid and integrated chemical analysis by utilizing the characteristics of micro space. In this thesis, the liquid-liquid system, termed a micro droplet collider, to utilize both of the spatial and temporal localized energy simultaneously is newly introduced by adding temporal localization to microfluidics. Liquid droplets in the gas phase confined in microchannels are used for spatial-temporal localization. A highly accelerated droplet generates the high kinetic energy in the spatial localization. Rapid collision enables the spatial and temporal localization of the high-energy, which induces the conversion and transfer of the high-energy to other work in the target.

In chapter 2, a micro droplet collider device which has launchers for the droplet shot, tracks for the droplet run and a chamber for the collision was designed based on the gas-liquid Laplace pressure and fabricated on a glass substrate. The velocity of droplet (0.25 nL) reached 920mm s-1 with the degree of acceleration of 2,300 m s-2 (230 G). The droplet velocity in the micro droplet collider is 102 times faster and the kinetic energy of the droplet is 104 times higher than the conventional droplet-based microfluidic methods. Rapid (< 1 ms), inelastic and minimally deformable collision between droplets was achieved, which enabled the utilization of the localized high-energy efficiently.

In chapter 3, droplet motion in acceleration and droplet internal flow in collision were investigated to clarify the basic physical properties by using a high-speed camera under microscope observation. It was confirmed that the droplet velocity reached maximum just after shot and became constant in the downstream of the microchannel track. The droplet terminal velocity increased as increasing the applied air pressure and reached 1.4 m s-1 when applying 400 kPa of air pressure. The fluorescent particles were seeded in the droplet to visualize the droplet internal flow and captured by a high-speed camera equipped with an image intensifier unit. The accelerated droplet was found to be penetrated into the stopping target droplet. The flow induced by collision was two orders of magnitude faster than that induced by shear stress of air flow after collision.

In chapter 4, two kinds of micro chemical processes which have not been achieved in the conventional microfluidic formats were realized by utilizing the spatial-temporal localized energy of the droplet. Rapid mixing between the nL order of droplets having a 1:10 volume ratio was achieved by inducing the internal flow by the droplet collision, which was 6,000 times faster than molecular diffusion. Integration of droplet process and parallel flow processes was achieved by injecting the accelerated droplet to the flow beyond the dynamic pressure.

The developed micro droplet collider is expected to contribute greatly to microfluidics and chemical processes on a microchip.

1.Introduction

In recent years, there has been great interest in microfluidic devices for miniaturizing chemical systems and integrating various chemical processes1. These devices have many advantages based on spatial localization of the liquid system, including short analysis time, low consumption of sample and reagent amounts, small waste volumes, effective reaction due to the large specific interfacial area, and small space requirement. In general, microfluidics can be divided into two categories. One is the continuous (including parallel) flow format2 and the other is the droplet-based format3. In the continuous flow format, for example, our group demonstrated the integration of fundamental chemical operations such as mixing, reactions, solvent extraction and multi-phase flow networking by applying surface chemistry. In the second category, the droplet-based format has focused on creating discrete volumes with the use of an immiscible phase. Primarily, water droplet-in-oil format have been widely studied. Droplet generation and manipulation such as transporting, fusion, mixing and sorting have been achieved by the steady laminar flow of the immiscible phase. All of the conventional approaches in microfluidics have intended to realize chemical processes inside the steady liquid flow and by molecular diffusion.

In this thesis, the liquid-liquid system, termed a micro droplet collider, to utilize both of the spatial and temporal localized energy simultaneously is newly introduced by adding temporal localization to microfluidics. Liquid droplets in the gas phase confined in microchannels are used for spatial-temporal localization. A highly accelerated droplet generates the high kinetic energy in the spatial localization and rapid collision enables the spatial and temporal localization of the high-energy, which induces the conversion and transfer of the high-energy to realize various novel chemical processes.

The objective of this study is to realize the micro droplet collider and to develop chemical processes. Specifically, this thesis addresses the following points. (1) The micro droplet collider is realized on a microchip (2) Dynamics of the micro droplet collider is investigated. (3) Chemical processes by utilizing the spatial-temporal localized liquid energy are developed.

2.Realization of a Micro Droplet Collider

In this chapter, the chip design to realize a micro droplet collider and performance evaluation of droplet acceleration and collision are described.

2.1Chip design

The designed microchip (Fig. 1) has the launcher for droplet shot, the microchannel track for droplet run, and the collision chamber for droplet collision. Through the whole chip design, the gas-liquid Laplace pressure is utilized. In the launcher, the droplet can be generated at the shallow hydrophobic Laplace valve and be accelerated by applying air pressure (Fig. 2). In the chamber, droplet collision can be conducted by holding the target droplet by Laplace pressure and eliminating air to the shallow hydrophobic side channel (Fig. 3).

2.2Performance evaluation

The velocity of droplet (0.25 nL) reached 920mm s-1 with the degree of acceleration of 2,300 m s-2 (230 G). The droplet velocity in the micro droplet collider is 102 times faster and the kinetic energy of the droplet is 104 times higher than the conventional droplet-based microfluidic methods. The rapid (< 1 ms), inelastic collision between droplets with minimally deformation was achieved in the micro droplet collider, which enabled the efficient utilization of the spatial-temporal localization energy in the liquid phase.

3.Investigation of Dynamics of the Micro Droplet Collider

In this chapter, dynamics of the micro droplet collider is investigated to optimize the system, to realize extreme performances, and to develop novel micro chemical processes.

3.1Investigation of a Droplet Motion in acceleration

The 1.7 nL of a droplet was generated and shot from the launcher by 20 kPa of air pressure. The droplet motion was captured by a high-speed camera (1,000~10,000 fps) under a microscope observation. It was confirmed that the droplet velocity reached maximum just after passing the shallow Laplace valve part and became constant in the downstream of the microchannel track as shown in Fig. 4. The droplet terminal velocity increased as increasing the applied air pressure and reached 1.4 m s-1 when applying 400 kPa of air pressure as shown in Fig. 5. Modeling of droplet motion and determination of dominant resistance force are described in this thesis.

3.2. Investigation of a Droplet Internal Flow in Collision

Droplet internal flow in the collision event was investigated to estimate how the energy of the accelerated droplet transfers and induces flow to the target droplet. The fluorescent particles were seeded in the droplet to visualize the flow and captured by a high-speed camera equipped with an image intensifier unit. Droplet internal flow induced by collision is shown in Fig. 6. The accelerated droplet was found to be penetrated into the stopping target droplet. The flow induced by collision was two orders of magnitude faster than that induced by shear stress of air flow after collision.

The results obtained in this chapter are useful to apply to chemical processes.

4.Application to Chemical Processes

In this chapter, micro chemical processes that have not been achieved yet are realized by utilizing the spatial-temporal localized energy of the droplet.

4.1. Mixing between Droplets Having a Large Volume Ratio

Mixing is basic and important in various bio/chemical processes. Mixing between droplets, especially in a large volume ratio, on a microscale is challenging because of a laminar flow regime and time-consuming molecular diffusion process. However, rapid mixing of two droplets having a 10:1 (Fig. 7) and 1:10 (Fig. 8) volume ratio was achieved by the collision of the accelerated droplet to the target. Mixing time was estimated as 0.5 s, which is more than 6,000 times faster than that of molecular diffusion.

4.2. Integration of Droplet and Parallel Flow Processes

Complicated chemical processes have been achieved under a network of parallel flow. In parallel flow processes, however, the batch processes such as liquid volume metering and injection of the metered liquid to the flow are difficult. Injection of a droplet to the flow has been difficult in the conventional droplet-in-oil format, because of the dynamic pressure of the flow and the difficulty of the oil phase elimination. Here, microchip was designed to control both the parallel flow and the droplet independently by utilizing the gas-liquid Laplace pressure. The droplet was accelerated toward the parallel flow and successfully injected beyond the dynamic pressure as shown in Fig. 9.

The developed micro chemical processes in this chapter would contribute to the bio/chemical analysis and extend applications of the microfluidic devices.

5.Concluding Remarks

In this thesis, the novel microfluidic device, termed the micro droplet collider, was developed. Micro chemical processes which have not been achieved yet were realized by the collision of the accelerated droplet to the target in the gas phase. In the future, bio/chemical analysis and reaction will be realized by utilizing the developed device.

Fig. 1. Micro droplet collider chip.

Fig. 2. Droplet shot from the launcher

Fig. 3. Droplet collision in the chamber.

Fig. 4. Droplet behaviors in the track. (upper) Captured image. (lower) Analyzed droplet position against time.

Fig. 5. Droplet terminal velocity against the applied air pressure.

Fig. 6. Droplet internal flow induced by collision.

Fig. 7. Results of mixing between droplets having a 10:1 volume ratio.

Fig. 8. Results of mixing between droplets having a 1:10 volume ratio

Fig. 9. Time-lapsed images of the droplet injection to the parallel flow

本論文は、「Developmentofanovelmicrofluidicdevicebyutilizingmicrodropletco11isionanditsapplicationtochemicalprocesses(マイクロ液滴衝突を用いた新規マイクロ流体デバイスの開発と化学プロセスへの展開)」と題し、制御閉空間であるマイクロチャネル内での液滴の加速と衝突により、液滴の運動エネルギーを時間・空間的に集中させることにより化学プロセスを実現する新規マイクロ流体デバイス、すなわちマイクロ液滴コライダーの創成に関する研究結果をまとめたものである。

第1章では、近年のμTASやLab-on-a-chipといわれる類似的研究の歴史的背景とその意義をまとめ、マイクロ化学システムの有用性を示した。また、従来のマイクロ流体プロセスについてまとめ、これはマイクロ空間のスケール効果のみを利用していることを示した。そして、これらの研究に対し、本研究の液滴の運動エネルギーを積極的に利用するマイクロ液滴コライダーの意義を明確にし、本研究の目的を述べた。

第2章では、創案したマイクロ液滴コライダーについて述べた。マイクロチャネル内での液滴の生成・発射・加速操作および高速衝突操作を1つのマイクロチップ上に集積化するために、気相中での液滴操作および気液ラプラス圧を用いた設計を着想した。設計・作製したチップを用いサブナノリットルオーダーの液滴を気液ラプラス圧を用いたバルブ機能により生成し、圧縮空気により発射・加速した。液滴速度はメートル毎秒オーダーとなり従来の油中液滴プロセスの100倍以上高速化を実現した。また、気液ラプラス圧を用いた衝突チャンバー設計により、標的液滴を保持した状態で、液滴間の気体を迅速排除し、加速液滴との高速衝突(衝突時間1ミリ秒以下)を実現した。表面張力制御など制御閉空間の効果を活用して、衝突位置・時間の制御、高速・非弾性の衝突を実現し、加速液滴の運動エネルギーを衝突により効率的に利用可能とした。本章の結果はマイクロ液滴コライダーの原理をはじめて実証したものである。

第3章では、マイクロ液滴衝突を高速で可視化計測し、衝突現象と流動現象を解析した。前章で開発したマイクロ液滴コライダーにおける流動ダイナミクスを解明し、化学プロセスに展開するため、液滴の高速運動を顕微鏡下の高速度カメラで可視化計測した。液滴は発射後、下流流路で終端速度に達し、印加圧力に比例して終端速度が増加することを示した。管摩擦係数を用いて液滴運動の支配因子について評価し、液滴運動には気体流れの影響が大きいことを示した。また、液滴の高速衝突時の内部流動を蛍光粒子を用いて可視化計測した。同一径を有する加速液滴でも、衝突後は標的液滴の中心部に貫入する特異な流動を見出した。衝突後の液滴形状等は表面張力で制御され、加速液滴が標的液滴に慣性により浸入することを示した。これは、液滴の運動エネルギーの集中による内部流動の誘起をはじめて実証したものである。従来のマイクロ液滴プロセスやバルク自由空間での液滴衝突では困難であった液滴の運動エネルギーを用いた化学プロセスが、制御閉空間での液滴衝突により可能であることを示した。

第4章では、マイクロ液滴コライダーを用いたマイクロ化学プロセスを開発した。従来の拡散支配のマイクロ流体プロセスでは困難である、体積の大きく異なる液滴問の迅速混合を実現した。加速液滴の運動エネルギーで衝突により標的液滴の内部流動を誘起することにより、体積比1:10の微量液滴間迅速混合(拡散の6,000倍迅速)を実現した。また、油中液滴操作やインクジェットなど従来法では困難だった平行流プロセスと液滴プロセスの融合を実現した。マイクロ液滴コライダーの圧縮空気を用いた加速機構と気液ラプラス圧を用いた流路設計により、液滴の平行流への撃ち込みを実現した。本章で開発したマイクロ化学プロセスにより、従来困難であった前処理を含むオンチップ血液分析、滴定分析、単一細胞分析といった複雑かつ広範囲の分析化学への展開が可能となる。

第5章では、第2章から第4章までで開発・解析したマイクロ液滴コライダーのマイクロ流体工学としての意義についてまとめ、展望を示した。

以上要約したように、本論文は、液滴の運動エネルギーを時間・空間的に集中するマイクロ液滴コライダーの創成により、従来困難であった様々な化学プロセスへの展開を実証したものである。今後、開発したデバイスの目的に応じた性能向上により、化学・バイオ分析および反応・合成化学への広範囲な応用が期待される。以上、本論文はバイオエンジニアリングの進展に貢献するものである。

よって本論文は博士(工学)の学位請求論文として合格と認められる。