本研究利用微機電系統製程技術，製作一個可調控微液滴成型之新型乳化微流體晶片。此微流體晶片在聚焦管道下游的兩側製作可動式側壁結構，利用壓縮空氣擠壓可動式側壁，使流體產生微乳化液滴並可控制微液滴進入搜集端偏移的角度。在固定流速的條件下，可動式側壁結構使局部流體壓力改變，藉此壓力的改變進而調控微液滴的尺寸。實驗資料顯示，新型乳化微流體晶片可形成直徑31.2到146.2 μm的微液滴，其尺寸誤差低於5.39%。另外，可動式側壁在微管道兩側可形成不對稱結構，在後端蒐集區可產生0到±53.5°的偏移，不需額外的分選即可分離出不同尺寸的微液滴至不同的角度。此外，更可藉由此平台生產具有磁性之海藻膠乳化液滴，並在後端進行固化步驟，即可製作出具有生物相容性之磁性海藻膠粒子，此微流體晶片系統對於微液滴的成型與分選是一容易操作且可靠的平台，相信未來在製藥、化妝及食品工業的應用都將是不可或缺的工具；而所製作之海藻膠磁珠，在生醫技術上更是經常使用此一特性進行免疫檢測、細胞分離、基因轉殖及其他多項應用。

Formation of emulsion droplets is crucial for a variety of industrial and scientific applications. This study presents a new microfluidic emulsion system capable of generating tunable and uniform-sized droplets and subsequently deflecting these droplets at various inclination angles using a combination of flow-focusing and moving-wall structures. A pneumatic air chamber was used to activate the moving-wall structures, located nearby the outlet of the flow-focusing microchannels, such that the sheath flows can be locally accelerated. The flow-focusing microchannel forced the continuous phase and disperse phase fluids to pass through a narrow orifice. With this approach, the size of the droplets can be fine-tuned and sorted without adjusting the syringe pumps. One can control the shear force by adjust the sheath flows velocities. Thus, the droplets size can be easily controlled by the moving-wall structure without changing the flow rate of a syringe pump. Experimental data showed that droplets with diameters ranging from 31.4 to 146.2 μm with a variation of less than 5.39% can be generated. Besides, by using different operation modes, droplets can be sorted upwards or backwards with an inclination angle ranging from 0° to 53.5°. Meanwhile, the droplet diameters and the inclination angle can be adjusted at the same time. By using a similar droplet-based platform, magnetic alginate particles was also produced and collected successfully. A two-stage process, using a flow focusing method to generate magnetic alginate droplets in n-hexadecane, and then dripped them into the cross-linking buffer for solidification, was reported. The magnetic alginate droplets with diameters ranging from 56.4 to 102.4 μm were generated. The development of this microfluidic emulsion platform for generation of magnetic alginate droplets may be promising for applications in pharmaceuticals, cosmetics and food industries.

[1] S. E. Friberg and K. Larsson, “Food emulsions,” Marcel Dekker Inc. USA., pp. 189-233, 1997.
[2] C. Wibowo and K. M. Ng, “Product-oriented process synthesis and development: creams and pastes,” AICHE J., vol. 47, pp. 2746-2767, 2001.
[3] 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,” J. Infect. Dis., vol. 80, pp. 1939-1949, 1999.
[4] A. V. Korobko, W. Jesse and van J. R. C. der Maarel, “Encapsulation of DNA by Cationic Diblock Copolymer Vesicles,” Langmuir, vol. 21, pp. 34 -42, 2005.
[5] 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 Res., vol. 33, pp. 150, 2005.
[6] S. M. Moghimi, A. C. Hunter and J. C. Murray “Nanomedicine: current status and future prospects,” Faseb J., vol. 19, pp. 311-330, 2005.
[7] S. M. Jafari, Y. He and B. Bhandari, “Nano-Emulsion Production by Sonication and Microfluidization - A Comparison,” Int. Food Prop., vol. 9, pp. 475-485, 2006.
[8] 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 & Surfaces A: Phys. Eng. Asp., vol. 209, pp. 83-104, 2002.
[9] C. Charcosset, I. Limayem and H. Fessi, “The membrane emulsification process - a review,” Journal of Chem. Technolo. and Biotechnolo., vol. 79, pp. 209-218, 2004.
[10] S. Sugiura, M. Nakajima, H. Kumazawa, and S. Iwamoto and M. Seki, “Characterization of Spontaneous Transformation-Based Droplet Formation during Microchannel Emulsification,” J. Phys. Chem., vol. 106, pp. 9405-9409, 2002.
[11] S. Sugiura, M. Nakajima, S. Iwamoto and M. Seki, “Interfacial Tension Driven Monodispersed Droplet Formation from Microfabricated Channel Array,” Langmuir, vol. 17, pp. 5562-5596, 2001.
[12] S. Sugiura, M. Nakajima and M. Seki, “Prediction of Droplet Diameter for Microchannel Emulsification,” Langmuir, Vol. 18, No. 10, pp. 3854-3859, 2002.
[13] T. Nisisako, T. Torii and T. Higuchi, “Droplet formation in a microchannel network,” Lab. Chip, vol. 2, pp. 24-26, 2002.
[14] 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, pp. 9905-9908, 2004.
[15] S. L. Anna, N. Bontoux and H. A. Stone, “Formation of dispersions using ‘flow-focusing’ in microchannels,” Applied Physics Letters., vol. 82, pp. 364-366, 2003.
[16] Y. C. Tan, V. Cristini and A. P. Lee, “Monodispersed microfluidic droplet generation by shear focusing microfluidic device,” Sens. Actuator B-Chem., vol. 114, pp. 350-356, 2006.
[17] P. Garstecki, I. Gitlin, W. DiLuzio and G. M. Whitesidesa, “Formation of monodisperse bubbles in a microfluidic flow-focusing device,” Appl. Phys. Lett., Vol. 85, No. 13, pp. 2649-251 , 2004.
[18] S. Takeuchi, P. Garstecki, D. B. Weibel and G. M. Whitesides, “An Axisymmetric Flow-Focusing Microfluidic Device,” Adv. Mater., vol. 17, pp. 1067-1072, 2005.
[19] L. Yobas, S. Martens, W. L. Ong and N. Ranganathan, “High-performance flow-focusing geometry for spontaneous generation of monodispersed droplets,” Lab. Chip, vol. 6, pp. 1073-1079, 2006.
[20] Y. C. Tan and A. P. Lee, “Microfluidic separation of satellite droplets as the basis of a monodispersed micron and submicron emulsification system,” Lab. Chip, vol. 6, pp.1178–1183, 2005.
[21] S. Xu, Z. Nie, M. Seo, P. Lewis, E. Kumacheva, H. A. Stone, P. Garstecki, D. B. Weibel, I. Gitlin and G. M. Whitesides, “Generation of monodisperse particles by using microfluidics: control over size, shape, and composition,” Angew. Chem. Int. Ed., vol. 44, pp. 724-728, 2005.
[22] T. Nisisako and T. Torii, “Microfluidic large-scale integration on a chip for mass production of monodisperse droplets and particles,” Lab. Chip, vol. 8, pp. 287–293, 2008.
[23] C. Zhou, P. Yue and J. J. Feng, “Formation of simple and compound drops in microfluidic devices,” Phys. Fluids, vol. 18, pp. 092105, 2006.
[24] S. K. Hsiung, C. T. Chen and G. B. Lee, “Micro-droplet formation utilizing microfluidic flow focusing and controllable moving-wall chopping techniques,” J. Micromech. Microeng., vol. 16, pp. 2403-2410, 2006.
[25] C. T. Chen and G. B. Lee, “Formation of micro-droplets in liquids utilizing active pneumatic choppers on a microfluidic chip,” J. Microelectromech. Syst., vol. 15, pp. 1492-1498, 2006.
[26] C. H. Lee, S. K. Hsiung and G. B. Lee, “A tunable microflow focusing device utilizing controllable moving walls and its applications for formation of micro-droplets in liquids,” J. Micromech. Microeng., vol. 17, pp. 1-9, 2007.
[27] G. B. Lee, C. I. Hung, B. J. Ke, G. R. Huang and B. H. Hwei, “Micromachined pre-focused 1 × N flow switches for continuous sample injection,” J. Micromech. Microeng., vol. 11, pp. 567–573, 2001.
[28] G. B. Lee, B. H. Hwei and G. R. Huang, “Micromachined pre-focused M × N flow switches for continuous multi-sample injection,” J. Micromech. Microeng., vol. 11, pp. 654–661, 2001.
[29] A. Desai, W. S. Kisaalita, C. Keith and Z. Z. Wu, “Human neuroblastoma (SH-SY5Y) cell culture and differentiation in 3-D collagen hydrogels for cell-based biosensing,” Biosens. Bioelectron., vol. 21, pp. 1483-1492, 2006.
[30] S. Brahim, D. Narinesingh and A. Guiseppi-Elie, “Bio-smart hydrogels: co-joined molecular recognition and signal transduction in biosensor fabrication and drug delivery,” Biosens. Bioelectron., vol. 17, pp. 973-981, 2002.
[31] L. W. Norton, E. Tegnell, S. S. Toporek and W. M. Reichert, “In vitro characterization of vascular endothelial growth factor and dexamethasone releasing hydrogels for implantable probe coatings,” Biomaterials, vol. 26, pp. 3285-3297, 2005.
[32] C. G. Gebelein, T. C. Cheng and V. C. Yang, ‘‘Cosmetic and Pharmaceutical Applications of Polymers’’, Plenum, New York 1991.
[33] G. L. Blackmer and R. H. Reynolds, “Composition and safety of cured meats in the USA,” J. Agric.Food Chem., Vol. 25, pp.561-566, 1977.
[34] M. El-Nakaly, D. M. Piatt and B. A. Charpentier, “Polymeric Delivery Systems, Properties and Applications,” American Chemical Society, Washington, D. C. 1993.
[35] M. Muraoka, Z. P. Hu, T. Shimokawa, S. Sekino, R. Kurogoshi, Y. Kuboi, Y. Yoshikawa and K. Takada, “Protective interactive noncondensing (PINC) polymers for enhanced plasmid distribution and expression in rat skeletal muscle,” J. Controlled Release, vol. 52, pp. 119-203, 1998.
[36] B. G. De Geest, J. P. Urbanski, T. Thorsen, J. Demeester and S. C. De Smedt, “Synthesis of Monodisperse Biodegradable Microgels in Microfluidic Devices,” Langmuir, vol. 21, pp. 10275-10279, 2005.
[37] D. Poncelet, R. Lencki, C. Beaulieu, J. P. Halle, R. J. Neufeid and A. Fournier, “Production of alginate beads by emulsification/internal gelation. I. Methodology,” Appl. Microbiol. Biotechnol., vol. 38, pp. 39-45, 1992.
[38] D. Poncelet , B. Poncelet De Smet, C. Beaulieu, M. L. Huguet, A. Fournier and R. J. Neufeld, “Production of alginate beads by emulsification/internal gelation.
II. Physicochemistry,” Appl. Microbiol. Biotechnol., vol. 43, pp. 644-650, 1995.
[39] D. Quong, R. J. Neufeld, G. Skjåk-Bræk and D. Poncelet, “External versus internal source of calcium during the gelation of alginate beads for DNA encapsulation,” Biotechnol. Bioeng., vol. 57, pp. 438-446, 1998.
[40] Victoria L. Workman, Stephen B. Dunnett, Peter Kille, Daniel and D. Palmer, “On-Chip Alginate Microencapsulation of Functional Cells,” Macromol. Rapid Commun., vol. 29, pp. 165-170, 2008.
[41] V. L. Workman, S. B. Dunnett, P. Kille and D. D. Palmera, “Microfluidic chip-based synthesis of alginate microspheres for encapsulation of immortalized human cells,” Biomicrofluidics, vol. 1, pp. 014105, 2007.
[42] F. Yang, K. Wang and Z. M. He, “Two new plate nozzles for the production of alginate microspheres,” Int. J. Pharm., vol. 298, pp.206-210, 2005.
[43] K. S. Huang, T. H. Lai and Y. C. Lin, “Manipulating the generation of Ca-alginate microspheres using microfluidic channels as a carrier of gold nanoparticles,” Lab Chip, vol. 6, pp. 954-957, 2006.
[44] L. Capretto, S. Mazzitelli, C. Balestra, A. Tosib and C. Nastruzzi, “Effect of the gelation process on the production of alginate microbeads by microfluidic chip technology,” Lab Chip, vol. 8, pp.617-621, 2008.
[45] C. Qiu, M. Chen, H. Yan and H. Wu, “Generation of Uniformly Sized Alginate Microparticles for Cell Encapsulation by Using a Soft-Lithography Approach,” Adv. Mater., vol. 19, pp. 1603-1607, 2007.
[46] H. Shintaku, T. Kuwabara, S. Kawano, T. Suzuki, I. Kanno and H. Kotera, “Micro cell encapsulation and its hydrogel-beads production using microfluidic device,” Microsyst. Technol., vol. 13, pp. 951–958, 2007.
[47] K. Liu, H. J. Ding, J. Liu, Y. Chen and X. Z. Zhao, “Shape-Controlled Production of Biodegradable Calcium Alginate Gel Microparticles Using a Novel Microfluidic Device,” Langmuir, vol. 22,pp. 9453-9457, 2006.
[48] W. C. Griffin, “Classification of surface-active agents by HLB”, J. Soc. Cosmetic Chemists, vol. 1, pp. 311-326, 1949.
[49] P. Aslani and R. A. Kennedy, “Studies on diffusion in alginate gels. I. Effect of cross-linking with calcium or zinc,” J. Control. Release, vol. 42, pp. 75-82, 1996.
[50] P. Gacesa, “Alginates”, Carbohydr. Polym., vol. 8, pp. 161–182, 1988.
[51] Data sheet for NANOTM SU-8 negative tone photoresists, formulations 50 & 100, released by MICRO-CHEM. Corp.
[52] S. Teotia and M. N. Gupta, “Purification of α-Amylases Using Magnetic Alginate Beads,” Appl. Biochem. Biotechnol., Vol. 90, pp. 211-220, 2001.
[53] D. Y. Lee, Y. I. Oh, D. H. Kim, K. M. Kim, K. N. Kim and Y. K. Lee, “Synthesis and Performance of Magnetic Composite Comprising Barium Ferrite and Biopolymer,” IEEE Trans. Magn., Vol. 40, No. 4, pp. 2961-2963, 2004.
[54] N. E. Simpson, C. L. Stabler, C. P. Simpson, A. Sambanis and I. Constantinidis, “The role of the CaCl2–guluronic acid interaction on alginate encapsulated βTC3 cells,” Biomaterials, vol. 25, pp. 2603-2610, 2004.