This article presents two different microfluidic schemes that are capable of emulsification and multi-step chemistry synthesis. With different integrated functions, PDMS micro-device is able to produce double emulsification with controllable geometries and composition; moreover, multi-step synthesis of semi-permeable micro-encapsulation in a single chip. Three-layered PDMS molding and bonding process is used to fabricate the proposed microfluidic devices with pneumatically actuated diaphragm valves constructed on top of specially designed fluidic-channels are utilized to generate, meter, trap, filter the droplets and, consequently, the encapsulation process. A governing computer program cooperating with a set of control hardware was employed to coordinate the actuation of the prototype system. In the prototype demonstration, droplets was generated with desired size and frequency by alternating the open and close period of diaphragm valve. Emulsion droplets functioning as templates and reactors. During the synthesis process, relatively small Na-alginate droplets are metered, trapped, and then drawn into relatively large CaCl2 droplets, while they react and form solid Ca-alginate micro-capsules on the interfaces. In addition, entrapment and transfer of the resulting capsules can also be performed on the same microfluidic system to further process Ca-alginate into semi-permeable alginate-poly-L-lysine (PLL). It has been demonstrated that: (1) both water-in-oil-in-oil and water-in-oil-in-water double emulsions can be produced; (2) the sizes of inner aqueous droplets and outer oil drops can be controlled independently; (3) adjacent oil drops with varying overall sizes, and both diameters and numbers of inner aqueous droplets can be produced; (4) multi-step reactions could be performed on droplet-in-droplet interfaces to synthesize alginate-PLL capsules; and (5) on demand, controlled encapsulation could be achieved on an integrated microfluidic system. As such, the demonstrated emulsification and multi-step synthesis schemes could potentially fulfill the real-time controllability on emulsion formation and micro-encapsulation, which is desired for a variety of biological and medical applications.

[1] B. J. Briscoe, et al., "A Review of Immiscible Fluid Mixing," Advanced in Colloid and Interface Science, vol. 81, pp. 1-17, 1999.
[2] Todd Thorsen, et al., "Dynamic Pattern Formation in a Vesicle-Generating Microfluidic Device," Physical Review Letters , vol. 86, pp. 4163–4166, 2001.
[3] T. Nisisako, et al., "Droplet Formation in a Microchannel Network," Lab on a Chip, vol. 2, pp. 24-26, 2002.
[4] V. Steijn, et al., "μ-PIV Study of the Formation of Segmented Flow in Microfluidic T-junctions," Chemical Engineering Science 2007, vol. 62, pp. 7505-7514, 2007.
[5] S. L. Anna, et al., "Formation of Dispersions Using “Flow Focusing” in Microchannels," Applied Physics Letters, vol. 82, pp. 364-366, 2003.
[6] A. K. Chesters, et al., "The Modeling of Coalescence Processes in Fluid-liquid Dispersions : A Review of Current Understanding," Chemical Engineering Research and Design , vol. 69, 1991.
[7] Lung-Hsin Hung, et al., "Alternating Droplet Generation and Controlled Dynamic Droplet Fusion in Microfluidic Device for CdS Nanoparticle Synthesis," Lab on a Chip, vol. 6, pp. 174-178, 2006.
[8] Xize Niu, et al., "Pillar-induced Droplet Merging in Microfluidic Circuits," Lab on a Chip, vol. 8, pp. 1837–1841, 2008.
[9] B-J Jin, et al., "Droplet Merging in a Straight Microchannel Using Droplet Size or Viscosity Difference," Journal of Micromechanics and Microengineering, vol. 20, 2010.
[10] S. Okushima, et al., "Controlled Production of Monodisperse Double Emusions by Two-Step Breakup in Microfluidic Devices," Langmuir, vol. 20, pp. 9905-9908, 2004.
[11] A. S. Utada, et al., "Monodisperse Double Emulsions Generated from a Microcapillary Device," Science, vol. 308, pp. 537-541, 2005.
[12] S. H. Huang, et al., "A Monolithically Three-Dimensional Flow-Focusing Device for Formation of Single/Double Emulsions in Closed/Open Microfluidic Systems," Journal of Micromechanics and Microengineering, vol. 16, pp. 2336-2344, 2006.
[13] E. C. Rojas, et al., "Controlled Release from a Nanocarrier Entrapped within a Microcarrier," Journal of Colloid and Interface Science,, vol. 301, pp. 617-623, 2006.
[14] Fu-Che Chang, et al., "Controlled double emulsification utilizing 3D PDMS microchannels," Journal of Micromechanics and Microengineering, vol. 18, p. 8, 2008.
[15] Ho Cheung Shum, et al., " Double Emulsion Templated Monidisperse Phospholipid Vesicles," Langmuir, vol. 24, pp. 7651-7653, 2008.
[16] Keng-Shiang Huang, et al., "Manipulating the generation of Ca-alginate microspheres using microfluidic channels as a carrier of gold nanoparticles," Lab on a Chip, vol. 6, pp. 954-957, 2006.
[17] Yuya Morimoto, et al., ""Housing" for Cells in Monodisperse Microcages," IEEE-MEMS, 2008.
[18] Yuya Morimoto, et al., "Monodisperse Semi-Permeable Microcapsules for Continuous Observation of Cells," Lab on a Chip, vol. 9, pp. 2217-2223, 2009.
[19] Liang-Yin Chu, et al., "Controllable Monodisperse Multiple Emulsions," Angewandte Chemie International Edition, vol. 46, pp. 8970-8974, 2007.
[20] J.G.M. Winkelman, et al., "Binary, Ternary and Quaternary Liquid–liquid Equilibria in 1-butanol, Oleic Acid, Water and N-heptane Mixtures," Fluid Phase Equilibria, vol. 284, pp. 71-79, 2009.
[21] Michael L. Chabinyc, et al., "An Integrated Fluorescence Detection System in Poly(dimethylsiloxane) for Microfluidic Applications," Analytical Chemistry, vol. 73, pp. 4491-4498, 2001.