微液滴製備技術廣泛的應用在各種實用領域，本研究以兩種不同設計的微流體晶片系統製作均勻性高之乳化液滴，且兩種乳化晶片皆可精密控制微液滴的均勻度。第一種乳化晶片創新結合微流體聚焦和氣動式流體阻斷器技術。實驗結果顯示可準確控制大小6μm到100μm的乳化液滴，根據計算誤差值在3％以內。在晶片操作上有三種主動控制液滴尺寸的方式，包括改變微流道中邊鞘流和樣品流的流速比、驅動氣動式阻斷裝置之氣壓量和氣動式流體阻斷器的作動頻率。此外更以單管道微型乳化晶片技術為基礎，以多管道式設計並配合氣動式流體阻斷器完成微型多管道式乳化晶片，共包括平行式微型多管道式乳化晶片以及向心狀式微型多管道式乳化晶片，本晶片之設計可有效完成大量產生高均勻性及均質性之微奈米尺寸乳化晶片。
第二種微乳化液滴晶片整合了微流體聚焦技術和移動壁式流體阻斷器，亦屬可調式乳化液滴晶片。在微流道中以水力的方式利用兩側之連續相液體及中央微管道之分散相液體首先利用微流體聚焦現象予以集中縮減至預定的尺寸。再搭配上另一新型流體阻斷結構，設置於微管道兩側之側向腔體結構，稱為移動壁，當壓縮空氣進入微管道兩側之側向腔體後，管道壁受氣體壓力之作用而產生形變，此形變可將預先水力聚焦的流體做阻斷的動作，並使用單一組電磁閥控制壓縮氣體之供應頻率，用以將液體阻斷成微滴狀，並可藉由改變對側向壁進氣時的頻率及氣壓而改變微液滴之尺寸。測試結果顯示輸入氣體壓力與移動壁所產生變形量之關係，當最大輸入壓力為30 psi時，可產生一最大變形量為62.5 μm。此移動壁的截面積為100 μm×50 μm。實驗結果亦顯示利用移動壁式微乳化晶片可成功產生直徑為10 μm ~120 μm之乳化液滴，所產生之液滴在均勻性方面也較優於以往的設計。
上述兩類新式微流體系統可以在乳液製程、奈米生醫和微液滴上做極為廣泛的運用，同時本研究也成功的利用流體阻斷器的技術產生膠原蛋白及海藻膠鈣液滴，使此一技術平台更進一步拓展至生物技術和藥物傳輸的領域。

The formation of micro-scale monodispersed emulsions is essential for a variety of applications. This investigation describes two new microfluidic systems that can form precisely sized and uniform microdroplets in liquids for emulsification applications. The first chip employs a novel combination of hydrodynamic flow focusing and new liquid-cutting devices. Experimental data indicate that microdroplets with diameters ranging from 6 to 100 microns can be generated with less than 3% variation. The size of the droplets is adjustable using methods which involve changing the relative sheath/sample flow rate ratios, the applied air pressure and the applied cutting frequency. Additionally, the focusing and cutting of multiple flows has been demonstrated to increase the emulsion process throughput. In this study, two chips with parallel and concentric layouts for multiple channel emulsion have been successfully demonstrated.
The second microfluidic chip can be also used to generate precise microdroplets in liquids by integrating a combination of two microfluidic techniques: microfluidic flow focusing and the controlling of a moving-wall structure. The microfluidic chip can generate uniform droplets with adjustable sizes. Dispersed-phase sample flow is initially hydrodynamically focused into a narrow stream using neighboring sheath flows that contain continuous-phase samples. Additionally, a novel chopping microstructure called “controllable moving walls”, which consists of a pair of side chambers orthogonally placed next to the sample flow channel, is adopted to generate microdroplets. The moving-wall structures can be deformed using external air pressure to cut the pre-focused stream into segments. Adjustable microdroplets with a uniform diameter can be formed by controlling the air injection frequency and the air pressure of the side-chambers. Experimental data show that a maximum deformation of 62.5 μm can be achieved at a pressure of 30 psi for a moving wall with dimensions of 100 μm x 50 μm. Microdroplets of uniform size between 10 μm and 120 μm can be successfully generated by varying the flow velocity ratios between the dispersed and continuous phases from 2 to 20. The microdroplets have a much more uniform size than those reported in previous studies.
These devices have produced collagen and Ca-alginate microsphere using the liquid-cutting technique, and show promise in various application including emulsification, nano-medicine and droplet-based microfluidics.

[1] N. Maluf, “An Introduction to Microelectromechanical Systems Engineering”, Artech House, Boston, 1, 2000.
[2] M. U. Kopp, A. J. de Mello and A. Manz, “Chemical Amplification: Continuous-Flow PCR on a Chip”, Science, 280, 1046-1048, 1998.
[3] M. A. Burns, B. N. Johnson, S. N. Brahmasandra, K. Handique, J. R. Webster, M. Krishnan, T. S. Sammarco, P. M. Man, D. Jones, D. Heldsinger, C. H. Mastrangelo and D. T. Burke, “An Integrated Nanoliter DNA Analysis Device”, Science, 282, 484-487, 1998.
[4] D. J. Harrison, K. Fluri, Z. Fan, C. S. Effenhauser and A. Manz, “Micromachining a Miniaturized Capillary Electrophoresis-Based Chemical Analysis System on a Chip”, Science, 261, 895-897, 1993.
[5] S. J. Haswell and V. Skelton, “Chemical and Biochemical Microreactors”, Trends in Analytical Chemistry, 19, 389-395, 2000.
[6] T. McCreedy, “Fabrication Techniques and Materials Commonly Used for the Production of Microreactors and Micro Total Analytical Systems”, Trends in Analytical Chemistry, 19, 396-401, 2000.
[7] K. Y. Lien, W.C. Lee, H. Y. Lei and G. B. Lee, “Integrated Micro Reverse Transcription Polymerase Chain Reaction Systems Using Super-paramagnetic beads for Virus Detection,” accepted for publishing, IEEE NEMS 2006, Zhuhai, China, January, 18-21, 2006.
[8] C. S. Liao, G. B. Lee, T. M. Hsieh, F. C. Huang, C. H. Wang, C. L. Fan, H. S. Liu and C. H. Luo, “Monitoring the cDNA Synthesis Utilizing Microfabricated Reverse Transcription Polymerase Chain Reaction Chip,” The 8th Annual Nano Engineering and MEMS conference, 2004.
[9] C. Y. Lee, J. L. Lin, C. S. Liao, F. C. Huang and G. B. Lee, “Integrated Microfluidic Systems for DNA Analysis”, IEEE International Conference on Robotics and Biomimetics, Aug. 22-25, 2004.
[10] T. Kawakatsu, Y. Kikuchi and M. Nakajima, “Regular-Sized Cell Creation in Microchannel Emulsification by Visual Microprocessing Method”, Journal of the American Oil Chemists' Society, 74, 317-321, 1997.
[11] T. Kawakatsu, H. Komori, M. Nakajima, Y. Kikuchi and T. Yonemoto, “Production of Monodispersed Oil-in-Water Emulsion Using Crossflow-Type Silicon Microchannel Plate”, Journal of Chemical Engineering of Japan, 32, 241-244, 1999.
[12] S. E. Friberg and K. Larsson, “Food emulsions”, Marcel Dekker Inc. USA. 189-233, 1997.
[13] C. Wibowo and K. M. Ng, “Product-oriented process synthesis and development: creams and pastes”, American Institute of Chemical Engineers Journal, 47, 2746-2767, 2001.
[14] T. Hamouda, M. M. Hayes, Z. Cao, R. Tonda, K. Johnson, D. C. Wright, J. Brisker, and J. R. Baker, “A novel surfactant nanoemulsion with broad-spectrum sporicidal activity against Bacillus species”, The Journal of Infectious Diseases, 180, 1939-1949,1999.
[15] A. V. Korobko, W. Jesse, and van J. R. C. der Maarel, “Encapsulation of DNA by Cationic Diblock Copolymer Vesicles”, Langmuir, 21, 34 -42, 2005.
[16] S. M. Moghimi, A. C. Hunter, and J. C. Murray “Nanomedicine: current status and future prospects”, Journal of the Federation of American Societies for Experimental Biology, 19, 311-330, 2005.
[17] T. Kojima, Y. Takei, M. Ohtsuka, Y. Kawarasaki, T. Yamane and H. Nakano, “PCR amplification from single DNA molecules on magnetic beads in emulsion: application for high-throughput screening of transcription factor targets”, Nucleic Acids Research, 33 (17), e150, 2005.
[18] G. T. Vladisavljevic and H. Schubert, “Preparation and analysis of oil-in-water emulsions with a narrow droplet size distribution using Shirasu-porous-glass (SPG) membranes”, Desalination, 144, 167-172, 2002.
[19] D. J. McClements, “Food Emulsions: Principles, Practice, and Techniques”, CRC Press, 1999.
[20] J. Tong, M. Nakajima, H. Nabetani, Y. Kikuchi and Y. Maruta, “Production of oil-in-water microspheres using a stainless steel microchannel”, Journal of Colloid and
Interface Science, 237, 239-248, 2001.
[21] T. Kawakatsu, G. Tragardh, Ch. Tragardh, M. Nakajima, N. Oda and T. Yonemoto,
“The effect of the hydrophobicity of microchannels and components in water and oil phase on droplet formation in microchannel water-in-oil emulsification”, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 179, 29-37, 2001.
[22] S. Sugiura, M. Nakajima, H. Ushijima, K. Yamamoto and M .Seki, “Preparation
characteristics of monodispersed water-in-oil emulsions using microchannel
emulsification”, Journal of Chemical Engineering of Japan, 34, 757-765, 2001.
[23] S. Suriura, M. Nakajima, and M. Seki, “Effect of channel structure on microchannel
emulsification”, Langmuir, 18, 5708-5712, 2002.
[24] S. Sugiura, M. Nakajima, H. Ushijima, K. Yamamoto and M. Seki, “Preparation characteristics of monodispersed water-in-oil emulsions using microchannel emulsification”, Journal of Chemical Engineering of Japan, 34, 757-765, 2001.
[25] H. Liu, M. Nakajima, and T. Kimura, “Production of monodispersed water-in-oil emulsions using polymer microchannels”, Journal of the American Oil Chemists' Society, 81, 705-711, 2004.
[26] S. Sugiura, M. Nakajima, S. Iwamoto and M. Seki, “Interfacial tension driven monodispersed droplet formation from microfabricated channel array”, Langmuir, 17, 5562-5566, 2001.
[27] V, Schroder and H, Schubert, “Production of emulsions using microporous, ceramic
membranes”, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 152, 103-109, 1999.
[28] A. J. Abrahamse, R. van Lierop, R. G. M. van der Sman, A. van der Padt and R. M.
Boom, “Analysis of droplet formation and interactions during cross-flow membrane
emulsification”, Journal of Membrane Science, 204, 125-137, 2002.
[29] N. C. Christov, D. N. Ganchev, N. D. Vassileva, N. D. Denkov, K. D. Danov and P. A. Kralchevsky, “Capillary mechanisms in membrane emulsification: oil-in-water emulsions stabilized by tween 20 and milk proteins”, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 209, 83-104, 2002.
[30] C. Charcosset, I. Limayem and H. Fessi, “The membrane emulsification process-a review,” Journal of Chemical Technology and Biotechnology, 79, 209-218, 2004.
[31] I. Kobayashi, M. Yasuno, S. Iwamoto, A. Shono, K. Satoh and M. Nakajima, “Microscopic observation of emulsion droplet formation from a polycarbonate membrane”, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 207, 185-196, 2002.
[32] I. Kobayashi and M. Nakajima, “Silicon array of elongated through-holes for monodisperse emulsion droplets”, American Institute of Chemical Engineers Journal, 48, 1639-1644, 2002.
[33] F. J. Zendejas, U. Srinivasan, W. J. Holtz, D. Keasling and R. T. Howe, “microfluidic
generation of tunable emulsions for templated monodisperse silica”, Proceedings of
Transducers 1995, 1473-1476, 2005.
[34] S. L. Anna, N. Bontoux and H. A. Stone, “Formation of dispersions using ‘flow-focusing’ in microchannels”, Applied Physics Letter, 82, 364-366, 2003.
[35] P. Garstecki, I. Gitlin, W. DiLuzio and G. M. Whitesides, “Formation of monodisperse bubbles in a microfluidic flow-focusing device”, Applied Physics Letter, 85, 2649-2651, 2004.
[36] Y. C. Tan, V. Cristini and A. P. Lee, “Monodispersed microfluidic droplet generation
by shear focusing microfluidic device”, Sensors and Actuators B: Chemical, 114, 350-356, 2005.
[37] T. Nisisako, T. Torii and T. Higuchi, “Droplet formation in a microchannel network”,
Lab on Chip, 2, 24-26, 2002.
[38] S. Haeberle, R. Zengerle and J. Ducree, “Monodisperse droplet trains and segmented
flow for centrifugal microfluidics”, Proceedings of 9th International Conference on
Miniaturized Systems for Chemistry and Life Sciences 2005, 635-637, 2005.
[39] T. Thorsen, R. W. Roberts, F. H. Arnold and S. R. Quake, “Dynamic pattern formation in a vesicle-generating microfluidic device,” Physical Review Letters, 86, 4163-4166, 2001.
[40] R. Dreyfus, P. Tabeling and H. Willaime, “Ordered and disordered patterns in two-phase flows in microchannels”, Physical Review Letters, 90, 144505, 2003.
[41] D. R. Link, S. L. Anna, D. A. Weitz and H. A. Stone, “Geometrically mediated breakup of drops in microfluidic devices”, Physical Review Letters, 92, 054503, 2004.
[42] T. Kawakatsu, G. Tra¨ga°rdh, Ch. Tra¨ga°rdh, M. Nakajima, N. Oda and T. Yonemoto, “The effect of the hydrophobicity of microchannels and components in water and oil phases on droplet formation in microchannel water-in-oil emulsification”, Colloids and Surfaces, 179, 29-37, 2001.
[43] S. Takeuchi, P. Garstecki, D. B. Weibel and G. M. Whitesides, “An Axisymmetric Flow-Focusing Microfluidic Device”, Advanced Materials, 17, 1067-1072, 2005.
[44] H. Karbstein, H. Schubert, “Developments in the continuous mechanical production of oil-in-water macro-emulsions”, Chemical Engineering and Processing, 34, 205-211, 1995.
[45] G. B. Lee, C. I. Hung, B. J. Ke, G. R. Huang, B. H. Hwei and H. F. Lai, “Hydrodynamic focusing for a micromachined flow cytometer”, ASME Journal of Fluids Engineering, 123, 672-679, 2001.
[46] R. J. Yang, C. C. Chang, S. B. Huang and G. B. Lee, “A new focusing model and switching approach for electrokinetic flow inside microchannels”, Journal of Micromechanics and Microengineering, 15, 2141-2148, 2005.
[47] G.. B Lee, B. H. Hwei and G. R. Huang, “Micromachined pre-focused MxN flow switches for continuous multi-sample injection”, Journal of Micromechanics and Microengineering, 11, 654-661, 2001.
[48] Data sheet for NANOTM SU-8 negative tone photoresists, formulations 50 & 100, released by MICRO-CHEM. Corp.
[49] C. H. Wang and G. B. Lee, “Automatic bio-sensing diagnostic chips integrated with micro-pumps and micro-valves for multiple disease detection”, Biosensors and Bioelectronics, 21, 419-425, 2005.
[50] D.T. Birnbaum, and L. Brannon-Peppas, “Microparticle Drug Delivery Systems”, Drug Delivery Systems in Cancer Therapy, Humana Press, Totowa, NJ, 117-135, 2003.