乳化是一種發展已久的技術，並且廣泛的應用在各種領域中，本篇將設計一微流體晶片進行雙重乳化，有別於傳統的乳化方式，通過調整各相流率可以簡單的改變內外層液珠大小及數量，並進行連續性的雙重乳化溶液產製，未來可以應用在藥物釋控與化工合成等領域。
本研究設計了兩階段微流道結構並且利用黃光微影技術製作了PDMS微流道晶片，第一階段流道採用菱形柱狀陣列設計進行第一次乳化，第二階段流道則採用流體聚焦型結構進行第二次乳化，實驗透過注射泵浦分別控制三個流率參數，調整第一階段連續相流率和分散相流率及第二階段連續相流率達到控制外層液珠尺寸以及內層液珠數量和尺寸。由實驗結果中發現，液珠尺寸會隨著流過第一階段菱形陣列柱排數增加而下降，當超過某數量排數時，液珠尺寸將停止穩定下降並呈現不穩定的變化，並且在相同總流率下，液珠尺寸亦會隨著第一階段流率比愈大而降低的趨勢，另外在第二階段流道實驗中，當固定第二階段分散相流率時，愈大的第二階段連續相流率，將得以生成出愈小的尺寸液珠，最後是合併流道實驗中，在其他流率參數固定下，外層液珠尺寸與內層液珠數量會隨著第一階段流率比的提高而增加，並且生成出的雙重乳化液珠，其外層液珠的尺寸介於70 µm至126 µm，而對應的內層液珠尺寸介於11 µm至36 µm，並可同時包覆液珠數量的範圍介於4至10顆。

In this study, we developed a microfluidic device for generating double emulsion droplets. This device consist of two different shaped microchannels, one with regularly spaced pillar array, the other is a common flow-focusing microchannel. Two immiscible fluids are injected into the inlet of the first part of the device and the fluids are split by the pillars and forming W/O emulsions. Then the W/O emulsions continuously flow into the flow-focusing microchannel as a dispersed phase and the DI water with surfactant also inject to the channel as a continuous phase which generated the W/O/W double emulsions.
The experimental data demonstrates that the droplet size depends strongly on flow rate and flow rate ratio in different phases. We use this device to produce double emulsion droplets which control not only the size and the number of inner droplets but also the size of outer droplets by changing the flow rate in different phases. In this study, we successfully generated the double emulsion droplets with 4 - 10 inner droplets with the size from 11 - 36 µm, and the size of the outer droplets corresponds to the inner droplets is 70 - 126 µm. Compare to published microfluidic devices, this device successfully generated W/O/W emulsions containing more inner droplets. Thus, this microfluidic device is high potential for several kinds of industrial applications.

[1] T. S. Kaminski, O. Scheler, and P. Garstecki, "Droplet microfluidics for microbiology: techniques, applications and challenges," Lab on a Chip, 10.1039/C6LC00367B vol. 16, no. 12, pp. 2168-2187, 2016, doi: 10.1039/C6LC00367B.
[2] K. E. Uhrich, S. M. Cannizzaro, R. S. Langer, and K. M. Shakesheff, "Polymeric Systems for Controlled Drug Release," Chemical Reviews, vol. 99, no. 11, pp. 3181-3198, 1999/11/10 1999, doi: 10.1021/cr940351u.
[3] P. Fernandez, V. André, J. Rieger, and A. Kühnle, "Nano-emulsion formation by emulsion phase inversion," Colloids and Surfaces A: Physicochemical and Engineering Aspects, vol. 251, no. 1, pp. 53-58, 2004/12/20/ 2004, doi: https://doi.org/10.1016/j.colsurfa.2004.09.029.
[4] S. van der Graaf, C. G. P. H. Schroën, and R. M. Boom, "Preparation of double emulsions by membrane emulsification—a review," Journal of Membrane Science, vol. 251, no. 1, pp. 7-15, 2005/04/01/ 2005, doi: https://doi.org/10.1016/j.memsci.2004.12.013.
[5] M. Iqbal, N. Zafar, H. Fessi, and A. Elaissari, "Double emulsion solvent evaporation techniques used for drug encapsulation," International Journal of Pharmaceutics, vol. 496, no. 2, pp. 173-190, 2015/12/30/ 2015, doi: https://doi.org/10.1016/j.ijpharm.2015.10.057.
[6] S. Ding, C. A. Serra, T. F. Vandamme, W. Yu, and N. Anton, "Double emulsions prepared by two–step emulsification: History, state-of-the-art and perspective," Journal of Controlled Release, vol. 295, pp. 31-49, 2019/02/10/ 2019, doi: https://doi.org/10.1016/j.jconrel.2018.12.037.
[7] A. Manz, N. Graber, and H. á. Widmer, "Miniaturized total chemical analysis systems: a novel concept for chemical sensing," Sensors and actuators B: Chemical, vol. 1, no. 1-6, pp. 244-248, 1990.
[8] D. B. Weibel and G. M. Whitesides, "Applications of microfluidics in chemical biology," Current opinion in chemical biology, vol. 10, no. 6, pp. 584-591, 2006.
[9] V. Srinivasan, V. K. Pamula, and R. B. Fair, "Droplet-based microfluidic lab-on-a-chip for glucose detection," Analytica Chimica Acta, vol. 507, no. 1, pp. 145-150, 2004.
[10] G. M. Whitesides, "The origins and the future of microfluidics," Nature, vol. 442, no. 7101, p. 368, 2006.
[11] N.-T. Nguyen and Z. Wu, "Micromixers—a review," Journal of micromechanics and microengineering, vol. 15, no. 2, p. R1, 2004.
[12] C.-Y. Lee, W.-T. Wang, C.-C. Liu, and L.-M. Fu, "Passive mixers in microfluidic systems: A review," Chemical Engineering Journal, vol. 288, pp. 146-160, 2016.
[13] G. Cai, L. Xue, H. Zhang, and J. Lin, "A review on micromixers," Micromachines, vol. 8, no. 9, p. 274, 2017.
[14] A. Bransky, N. Korin, M. Khoury, and S. Levenberg, "A microfluidic droplet generator based on a piezoelectric actuator," Lab on a Chip, vol. 9, no. 4, pp. 516-520, 2009.
[15] W. Na, J. Kim, H. Lee, B. Yoo, and S. Shin, "Asymmetric fluttering ferromagnetic bar-driven inertial micropump in microfluidics," Biomicrofluidics, vol. 12, no. 1, p. 014115, 2018.
[16] T. Tofteberg, M. Skolimowski, E. Andreassen, and O. Geschke, "A novel passive micromixer: lamination in a planar channel system," Microfluidics and Nanofluidics, journal article vol. 8, no. 2, pp. 209-215, February 01 2010, doi: 10.1007/s10404-009-0456-z.
[17] T. W. Lim et al., "Three-dimensionally crossing manifold micro-mixer for fast mixing in a short channel length," Lab on a Chip, 10.1039/C005325M vol. 11, no. 1, pp. 100-103, 2011, doi: 10.1039/C005325M.
[18] Y. Lin, X. Yu, Z. Wang, S.-T. Tu, and Z. Wang, "Design and evaluation of an easily fabricated micromixer with three-dimensional periodic perturbation," Chemical Engineering Journal, vol. 171, no. 1, pp. 291-300, 2011/06/15/ 2011, doi: https://doi.org/10.1016/j.cej.2011.04.003.
[19] W. Raza, S. Hossain, and K.-Y. Kim, "Effective mixing in a short serpentine split-and-recombination micromixer," Sensors and Actuators B: Chemical, vol. 258, pp. 381-392, 2018/04/01/ 2018, doi: https://doi.org/10.1016/j.snb.2017.11.135.
[20] H. M. Xia, Z. P. Wang, Y. X. Koh, and K. T. May, "A microfluidic mixer with self-excited ‘turbulent’ fluid motion for wide viscosity ratio applications," Lab on a Chip, 10.1039/B925025E vol. 10, no. 13, pp. 1712-1716, 2010, doi: 10.1039/B925025E.
[21] N.-T. Nguyen and Z. Wu, "Micromixers—a review," Journal of Micromechanics and Microengineering, vol. 15, no. 2, pp. R1-R16, 2004/12/09 2004, doi: 10.1088/0960-1317/15/2/r01.
[22] E. Albina et al., "Tick-borne virus detection in Caribbean ticks using NGS and high-throughput microfluidic real-time PCR (DOMOTICK Project)," 2018: ESVV.
[23] S. C. Kim, I. C. Clark, P. Shahi, and A. R. Abate, "Single-cell RT-PCR in microfluidic droplets with integrated chemical lysis," Analytical chemistry, vol. 90, no. 2, pp. 1273-1279, 2018.
[24] S. H. Lee et al., "Bubble-free rapid microfluidic PCR," Biosensors and Bioelectronics, vol. 126, pp. 725-733, 2019/02/01/ 2019, doi: https://doi.org/10.1016/j.bios.2018.10.005.
[25] B. Okumus et al., "Single-cell microscopy of suspension cultures using a microfluidics-assisted cell screening platform," Nature protocols, vol. 13, no. 1, p. 170, 2018.
[26] C. Kantak, Q. Zhu, S. Beyer, T. Bansal, and D. Trau, "Utilizing microfluidics to synthesize polyethylene glycol microbeads for Förster resonance energy transfer based glucose sensing," Biomicrofluidics, vol. 6, no. 2, p. 022006, 2012.
[27] T. Thorsen, R. W. Roberts, F. H. Arnold, and S. R. Quake, "Dynamic Pattern Formation in a Vesicle-Generating Microfluidic Device," Physical Review Letters, vol. 86, no. 18, pp. 4163-4166, 04/30/ 2001, doi: 10.1103/PhysRevLett.86.4163.
[28] J. Nunes, S. Tsai, J. Wan, and H. A. Stone, "Dripping and jetting in microfluidic multiphase flows applied to particle and fibre synthesis," Journal of physics D: Applied physics, vol. 46, no. 11, p. 114002, 2013.
[29] C. Cramer, P. Fischer, and E. J. Windhab, "Drop formation in a co-flowing ambient fluid," Chemical Engineering Science, vol. 59, no. 15, pp. 3045-3058, 2004.
[30] P. Guillot, A. Colin, and A. Ajdari, "Stability of a jet in confined pressure-driven biphasic flows at low Reynolds number in various geometries," Physical Review E, vol. 78, no. 1, p. 016307, 2008.
[31] S. L. Anna, N. Bontoux, and H. A. Stone, "Formation of dispersions using “flow focusing” in microchannels," Applied physics letters, vol. 82, no. 3, pp. 364-366, 2003.
[32] G. F. Christopher and S. L. Anna, "Microfluidic methods for generating continuous droplet streams," Journal of Physics D: Applied Physics, vol. 40, no. 19, p. R319, 2007.
[33] P. Garstecki, M. J. Fuerstman, H. A. Stone, and G. M. Whitesides, "Formation of droplets and bubbles in a microfluidic T-junction—scaling and mechanism of break-up," Lab on a Chip, 10.1039/B510841A vol. 6, no. 3, pp. 437-446, 2006, doi: 10.1039/B510841A.
[34] E. Amstad, S. S. Datta, and D. Weitz, "The microfluidic post-array device: high throughput production of single emulsion drops," Lab on a Chip, vol. 14, no. 4, pp. 705-709, 2014.
[35] S. Akbari, T. Pirbodaghi, R. D. Kamm, and P. T. Hammond, "A versatile microfluidic device for high throughput production of microparticles and cell microencapsulation," Lab on a Chip, vol. 17, no. 12, pp. 2067-2075, 2017.
[36] C. Xu and Y. Chu, "An oscillating feedback microextractor with asymmetric feedback channels," Chemical Engineering Journal, vol. 253, pp. 438-447, 2014/10/01/ 2014, doi: https://doi.org/10.1016/j.cej.2014.05.078.
[37] C. Xu and Y. Dai, "High-Throughput Production of Droplets Using Mini Hydrodynamic Focusing Devices with Recirculation," Industrial & Engineering Chemistry Research, vol. 54, no. 25, pp. 6551-6558, 2015/07/01 2015, doi: 10.1021/acs.iecr.5b01114.
[38] A. S. Utada, E. Lorenceau, D. R. Link, P. D. Kaplan, H. A. Stone, and D. A. Weitz, "Monodisperse Double Emulsions Generated from a Microcapillary Device," Science, vol. 308, no. 5721, pp. 537-541, 2005, doi: 10.1126/science.1109164.
[39] L.-Y. Chu, A. S. Utada, R. K. Shah, J.-W. Kim, and D. A. Weitz, "Controllable Monodisperse Multiple Emulsions," Angewandte Chemie International Edition, vol. 46, no. 47, pp. 8970-8974, 2007, doi: 10.1002/anie.200701358.
[40] L. L. A. Adams, T. E. Kodger, S.-H. Kim, H. C. Shum, T. Franke, and D. A. Weitz, "Single step emulsification for the generation of multi-component double emulsions," Soft Matter, 10.1039/C2SM25953B vol. 8, no. 41, pp. 10719-10724, 2012, doi: 10.1039/C2SM25953B.
[41] S. Okushima, T. Nisisako, T. Torii, and T. Higuchi, "Controlled Production of Monodisperse Double Emulsions by Two-Step Droplet Breakup in Microfluidic Devices," Langmuir, vol. 20, no. 23, pp. 9905-9908, 2004/11/01 2004, doi: 10.1021/la0480336.
[42] A. R. Abate and D. A. Weitz, "High-Order Multiple Emulsions Formed in Poly(dimethylsiloxane) Microfluidics," Small, vol. 5, no. 18, pp. 2030-2032, 2009, doi: 10.1002/smll.200900569.
[43] P. E. N. P. SU-8 2000 - MicroChem, PROCESSING GUIDELINES FOR: SU-8 2025, SU-8 2035, SU-8 2035 and SU-8 2075, website: www.microchem.com/.
[44] C.-H. Yeh, Y.-C. Chen, and Y.-C. Lin, "Generation of droplets with different concentrations using gradient-microfluidic droplet generator," Microfluidics and Nanofluidics, journal article vol. 11, no. 3, pp. 245-253, September 01 2011, doi: 10.1007/s10404-011-0791-8.
[45] C.-H. Yeh and Y.-C. Lin, "Using a cross-flow microfluidic chip for monodisperse UV-photopolymerized microparticles," Microfluidics and Nanofluidics, journal article vol. 6, no. 2, pp. 277-283, February 01 2009, doi: 10.1007/s10404-008-0333-1.