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 Soft  Vol.1 No.1 , December 2012
Structured Microgels through Microfluidic Assembly and Their Biomedical Applications
Abstract: Droplet based microfluidic is an effective, versatile and scalable approach which can be used to produce structured microgels with desirable features. The high degree of control endowed with microfluidics enables the formation of various functional microgels such as multicompartment encapsulations, Janus shaped particles and non spherical microgels. These microgels have aroused great interest in biological engineering aspect, since they outperform their counterparts produced from other techniques and have been applied in drug delivery, 3 Dimensional cell culture, micro tissues, single cell assay, tissue engineering and bioimaging. In this review, we will summarize the fabrication processes, technology comparisons and the usages in biomedical applications.
Cite this paper: Luo, R. and Chen, C. (2012) Structured Microgels through Microfluidic Assembly and Their Biomedical Applications. Soft, 1, 1-23. doi: 10.4236/soft.2012.11001.
References

[1]   J. W. Kim, A. S. Utada, A. F. Nieves, Z. B. Hu and D. A. Weitz, “Fabrication of Monodisperse Gel Shells and Func- tional Microgels in Microfluidic Devices,” Angewandte Chemie International Edition, Vol. 46, No. 11, 2007, pp. 1819-1822. doi:10.1002/anie.200604206

[2]   Y. Qiu and K. Park, “Environment-Sensitive Hydrogels for Drug Delivery,” Advanced Drug Delivery Reviews, Vol. 53, No. 3, 2001, pp. 321-339. doi:10.1016/S0169-409X(01)00203-4

[3]   R. Langer and N. A. Peppas, “Advances in Biomaterials, Drug Delivery and Bionanotechnology,” AIChE Journal, Vol. 49, No. 12, 2003, pp. 2990-3006. doi:10.1002/aic.690491202

[4]   S. Seiffert and D. A. Weitz, “Microfluidic Fabrication of Smart Microgels from Macromolecular Precusors,” Poly- mer, Vol. 51, No. 25, 2010, pp. 5883-5889. doi:10.1016/j.polymer.2010.10.034

[5]   S. Abraham, E. H. Jeong, T. Arakawa, S. Shoji, K. C. Kim, I. Kim and J. S. Go, “Microfluidic Assisted Syn- thesis of Well-Defined Spherical Polymeric Microcap- sules and Their Utilization as Potential Encapsulants,” Lab Chip, Vol. 6, No. 6, 2006, pp. 752-756. doi:10.1039/b518006f

[6]   G. F. Christopher and S. L. Anna, “Microfluidic Methods for Generating Continuous Droplets Stream,” Journal of Physics D: Applied PhysicsEmail alert RSS feed, Vol. 40, No. 19, 2007, pp. R319. doi:10.1088/0022-3727/40/19/R01

[7]   J. D. Wan, “Microfluidic-Based Synthesis of Hydrogel Particles for Cell Microencapsulation and Cell-Based Drug Delivery,” Polymer, Vol. 4, No. 4, 2012, pp. 1084- 1108. doi.10.3390./polymer4021084

[8]   J. D. Wan, A. Bick, M. Sullivan, H. A. Stone, “Con- trollable Microfluidic Production of Microbubbles in Water-In-Oil Emulsion and the Formation of Porous Microparticles,” Advanced Materials, Vol. 20, No. 17, 2008, pp. 3314-3318. doi:10.1002/adma.200800628

[9]   M. Seo, Z. H. Nie, S. Q. Xu, M. Mok, P. C. Lewis, R. Graham and E. Kumacheva, “Continuous Microfluidic Reactors for Polymer Particles,” Langmuir, Vol. 21, No. 25, 2005, pp. 11614-11622. doi:10.1021/la050519e

[10]   D. Dendukuri and P. S. Doyle, “The Synthesis and Assem- bly of Polymeric Microparticles Using Microfluidics,” Advanced Materials, Vol. 21, No. 41, 2009, pp. 1-16. doi:10.1002/adma.200803386

[11]   B. Kintses, L. D. Van Vliet, S. R. A. Devenish and F. Holfelder, “Microfluidic Droplets: New Integrated Work- flows for Biological Experiments,” Current Opinion in Chemical Biology, Vol. 14, No. 5, 2010, pp. 548-555. doi:10.1016/j.cbpa.2010.08.013

[12]   A. B. Theberge, F. Courtois, Y. Schaerli, M. Fischlechner, C. Abell, F. Hollfelder and W. T. S. Huck, “Microdrop- lets in Microfluidics: an Evolving Platform for Discove- ries in Chemistry and Biology,” Angewandte Chemie International Edition, Vol. 49, No. 34, 2010, pp. 5846- 5868. doi:10.1002/anie.200906653

[13]   R. L. Srinivas, S. C. Chapin and P. S. Doyle, “Aptamer- Functionalized Microgel Particles for Protein Detection,” Analytical Chemistry, Vol. 83, No. 23, 2011, pp. 9138- 9145. doi:10.1021/ac202335u

[14]   C. Berkland, K. Kim, D. W. Pack, “Precision Polymer Microparticles for Controlled-Release Drug Delivery,” ACS Symposium Series, Vol. 879, Chapter 14, 2004, pp. 197-213.

[15]   B. Rotman, “Measurement of Activity of Single Mole- cules of β-D-Galactosidase,” Proceedings of the National Academy Science of USA, Vol. 47, No. 12, 1961, pp. 1981-1991. doi:10.1073/pnas.47.12.1981

[16]   J. K. Oh, R. Drumright, D. J. Siewart and K. Matyjas- zewski, “The Development of Microgels/Nanogels for Drug Delivery Application,” Progress in Polymer Science, Vol. 33, No. 4, 2008, pp. 448-477. doi:10.1016/j.progpolymsci.2008.01.002

[17]   H. C. Shum, A. R. Abate, D. lee, A. R. Studart, B. G. Wang, C. H. Chen, J. L. Thiele, R. K. Shah, A. Krummel and D. A. Weitz, “Droplet Microfluidic for Fabrication of Non-Spherical Particles,” Macromolecular Rapid Commu- nications, Vol. 31, No. 2, 2010, pp. 108-118. doi:10.1002/marc200900590

[18]   M. Marquis, D. Renard, and B. Cathala, “Microfluidic Generation and Selective Degradation of Biopoly-mer- Based Janus Microbeads,” Biomacromolecules, Vol. 13, No. 4, 2012, pp. 1197-1203. doi:10.1021/bm300159u

[19]   B. K. Lee, Y. H. Yun, J. S. Choi, Y. C. Choi, J. D. Kim and Y. W. Cho, “Fabrication of Drug-Loaded Polymer Mi- croparticles with Arbitrary Geometries Using a Piezo- electric Inject Printing System,” International Journal of Pharmaceutics, Vol. 427, No. 2, 2012, pp. 305-310. doi:10.1016/j.ijpharm.2012.02.011

[20]   F. Ikkai, S. Iwamoto, E. Adachi and M. Nakajima, “New Method of Producing Mono-Sized Polymer Gel Particles Using Microchannel Emulsification and UV Irradiation,” Colloid and Polymer Science, Vol. 283, No. 10, 2005, pp. 1149-1153. doi:10.1007/s00396-005-1271-z

[21]   Z. Q. Chang, C. A. Serra, M. Bouquey, L. Prat and G. Hadziioannou, “Co-Axial Capillaries Microfluidic Device for Synthesizing Size- and Morphology-Controlled Poly- mer Core-Polymer Shell Particles,” Lab Chip, Vol. 9, No. 20, 2009, pp. 3007-3011. doi:10.1039/b913703c

[22]   M. Zourob, S. Mohr, A. G. Mayes, A. Macaskill, N. Perez- moral, P. R. Fielden and N. J. Goddard, “A Micro-Reac- tor for Preparing Uniform Molecularly Imprinted Polymer Beads,” Lab Chip, Vol. 6, No. 2, 2006, pp. 296-301. doi:10.1039/b513195b

[23]   E. Brouzes, “Droplet Microfluidics for Single-Cell Analy- sis,” Methods in Molecular Biology, Vol. 853, No. 10, 2012, pp. 105-139. doi.10.1007/978-1-61779-567-1_10

[24]   H. Song, D. L. Chen, R. F. Ismagilov, “Reactions in Drop- lets in Microfluidic Channels,” Angewandte Chemie Inter- national Edition, Vol. 45, No. 44, 2006, pp. 7336-7365. doi:10.1002/anie.200601554

[25]   K. S. Huang, T. H. Lai and Y. C. Lin, “Manipulating the Generation of Ca-Alginate Microspheres Using Micro- fluidic Channels as a Carrier of Gold Nanoparticles,” Lab Chip, Vol. 6, No. 7, 2006, pp. 954-957. doi.10.1039/B606424H

[26]   P. Garstecki, M. J. Fuerstman, H. A. Stoen and G. M. Whiteside, “Formation of Droplets and Bubbles in a Micro- fluidic T-Junction-Scaling and Mechanism of Break-Up,” Lab Chip, Vol. 6, No. 3, 2006, pp. 437-446. doi:10.1039/b510841a

[27]   C. N. Baroun, F. Gallaire and R. Dangla, “Dynamics of Microfluidic Droplets,” Lab Chip, Vol. 10, No. 16, 2010, pp. 2032-2045. doi:10.1039/c001191f

[28]   Z. H. Nie, M. S. Seo, S. Q. Xu, P. C. Lewis, M. Mok, E. Kumacheva, G. M. Whitesides, P. Garstecki and H. A. Stone, “Emulsification in a Microfluidic Flow-Focusing Device: Effect of the Viscosities of the Liquids,” Micro- fluid Nanofluid, Vol. 5, No. 5, 2008, pp. 585-594. doi:10.1007/s10404-008-0271-y

[29]   M. Seo, I. Gorelikov, R. Williams and N. Matsuura, “In- fluence of Electrolyte Composition on the Photovoltaic Performance and Stability of Dye-Sensitized Solar Cells with Multiwalled Carbon Nanotube Catalysts,” Langmuir, Vol. 26, No. 12, 2010, pp. 13855-13860. doi:10.1021/la100406p

[30]   L. S. Roach, H. Song, R. F. Ismagilov, “Controlling Non- Specific Protein Adsorption in a Plug-Based Microfluidic System by Controlling Interfacial Chemistry Using Fluo- rous-Phase Surfactants,” Analytical Chemistry, Vol. 77, No. 3, 2005, pp. 785-796. doi:10.1021/ac049061w

[31]   J. W. Choi, D. K. Kang, H. Park, A. J. deMello and S. I. Chang, “High-Throughput Analysis of Protein-Protein In- teractions in Picoliter-Volume Droplets Using Fluore- scence Polarization,” Analytical Chemistry, Vol. 84, No. 8, 2012, pp. 3849-3854.doi:10.1021/ac300414g

[32]   S. Y. Jung, S. T. Retterer and C. P. Collier, “Interfacial Tension Controlled Fusion of Individual Femolitre Drop- lets and Triggering of Confined Chemical Reactions on Demand,” Lab Chip, Vol. 10, No. 24, 2010, pp. 3373- 3376. doi.10.1039/C0LC00376J

[33]   M. Meier, J. Kennedy-Darling, S. H. Choi, E. M. Nor- strom, S. S. Sisodia and R. F. Ismagilov, “Plug-Based Micro- fluidics with Defined Surface Chemistry to Miniaturize and Control Aggregation of Amyloidogenic Peptides,” An- gewandte Chemie International Edition, Vol. 48, No. 8, 2009, pp. 1487-1489.

[34]   J. Clausell-Tormos, D. Lieber, J. C. Baret, A. Ei-Harrak, O. J. Miller, L. Frenz, J. Blouwolff, K. J. Humphry, S. Koster, H. Duan. C. Holtze, D. A. Weitz, A. D. Griffiths and C. A. Merten, “Droplet-Based Microfluidic Platforms for the Encapsulation and Screening of Mammalian Cells and Multicellular Organisms,” Chemical Biology, Vol. 15, No. 7, 2008, pp. 427-437.

[35]   A. P. Aijian, D. Chatterjee and R. L. Garrell, “Fluorinated Liquid-Enabled Protein Handing and Surfactant-Aided Crystallization for Fully in Situ Digital Microfluidic MADI-MS Analysis,” Lab Chip, Vol. 12, No. 14, 2012, pp. 2552-2559. doi:10.1039/c2lc21135a

[36]   C. Holtze, A. C. Rowat, J. J. Agresti, J. B. Hutchison, F. E. Angile, C. H. J. Schmitz, S. Koster, H. Duan, K. J. Humphry, R. A. Scanga, J. S. Johnson, D. Pisignano and D. A. Weitz, “Biocompatible Surfactants for Water-In- Fluorocarbon Emulsions,” Lab Chip, Vol. 8, No. 10, 2008, pp. 1632-1639. doi:10.1039/b806706f

[37]   C. H. Chen, A. Sarkar, Y. A. Song, M. A. Miller, S. J. Kim, L. G. Griffith, D. A. Lauffenburger and J. Y. Han, “Enhancing Protease Activity Assay in Droplet-Based Mi- crofluidics Using a Biomolecule Concentrator,” Journal of American Chemical Society, Vol. 133, No. 27, 2011, pp. 10368-10371. doi:10.1021/ja2036628

[38]   J. C. Baret, “Surfactants in Droplet-Based Microfluidics,” Lab Chip, Vol. 12, No. 3, 2012, pp. 422-433. doi:10.1039/c1lc20582j

[39]   D. Velasco, E. Tumarkin and E. Kumacheva, “Micro- fluidic Encapsulation of Cells in Polymer Microgels,” Small, Vol. 8, No. 11, 2012, pp. 1633-1642. doi:10.1002/smll.201102464

[40]   E. Tumarkin and E. Kumacheva, “Microfluidic Genera- tion of Microgels from Synthetic and Natural Polymers,” Chemical Society Reviews, Vol. 38, No. 8, 2009, pp. 2161- 2168. doi:10.1039/b809915b

[41]   E. Kumacheva and P. Garstecki, “Microfluidic Reactors for Polymer Particles,” John Wiley & Sons, New York, 2011.

[42]   T. Thorsen, R. W. Roberts, F. H. Arnold and S. R. Quake, “Dynamic Pattern Formation in a Vesicle-Generating Mi- crofluidic Device,” Physical Review Letters, Vol. 86, No. 18, 2001, pp. 4163-4166. doi:10.1103/PhysRevLett.86.4163

[43]   C. Priest, S. Herminghaus and R. Seemann, “Generation of Monodisperse Gel Emulsion in a Microfluidic Device,” Applied Physical Letters, Vol. 88, No. 2, 2006, 3 p. doi:10.1063/1.2164393

[44]   A. R. Abate, A. Poitzsch, Y. Hwang, J. Lee, J. Czerwin- ska and D. A. Weitz, “Impact of Inlet Channel Geome- try on Microfluidic Drop Formation,” Physical Review E, Vol. 80, No. 2, 2009, 5 p. doi:10.1103/PhysRevE.80.026310

[45]   I. Kobayashi, S. Mukataka and M. Nakajima, “Production of Monodisperse Oil-in-Water Emulsion Using a Large Silicon Straight-Through Microchannel Plate,” Industrial & Engineering Chemisrty Research, Vol. 44, No. 15, 2005, pp. 5852-5856. doi:10.1021/ie050013r

[46]   I. Kobayashi, K. Uemura and M. Nakajima, “Formulation of Monodisperse Emulsions Using Submicron-Channel Arrays,” Colloids and Surfaces A: Physicochemical and Engineering Aspects, Vol. 296, No. 1-3, 2007, pp. 285- 289. doi:10.1016/j.colsurfa.2006.09.015

[47]   I. Kobayashi, M. Nakajima, H. Nabetani, Y. J. Kikuchi, A. Shohno and K. Satoh, “Preparation of Micron-Scale Mono- disperse Oil-in-Water Microspheres by Microchannel Emul- sification,” Journal of the American Oil Chemists’ Society, Vol. 78, No. 8, 2001, pp. 797-802. doi:10.1007/s11746-001-0345-5

[48]   M. T. Guo, A. Rotem, J. A. and D. A. Weitz, “Droplet Microfluidics for High-Throughput Biological Assays,” Lab Chip, Vol. 12, No. 12, 2012, pp. 2146-2155. doi:10.1039/c2lc21147e

[49]   S. Y. Teh, R. Lin, L. H. Hung and A. P. Lee, “Droplet Microfluidics,” Lab Chip, Vol. 8, No. 2, 2008, pp. 198- 220. doi:10.1039/b715524g

[50]   H. N. Yow and A. F. Routh, “Formation of Liquid Core- Polymer Shell Microcapsules,” Soft Matter, Vol. 2, No. 11, 2006, pp. 940-949. doi:10.1039/b606965g

[51]   T. Kanai, D. Lee, H. C. Shum and D. A. Weitz, “Fabri- cation of Tunable Spherical Colloidal Crystals Immo- bilized in Soft Hydrogels,” Small, Vol. 6, No. 7, 2010, pp. 807-810. doi:10.1002/smll.200902314

[52]   S. Seiffert, J. Dubbert, W. Richtering, D. A. Weitz, “Re- duced UV Light Scattering in PDMS Microfluidic De- vices,” Lab Chip, Vol. 11, No. 5, 2011, pp. 966-968. doi:10.1039/c0lc00594k

[53]   P. Panda, S. Ali, E. Lo, B. G. Chung, T. A. Hatton, A. Khademhosseini and P. S. Doyle, “Stop-Flow Lithogra- phy to Generate Cell-Laden Microgel Particles,” Lab Chip, Vol. 8, No. 7, 2008, pp. 1056-1061. doi:10.1039/b804234a

[54]   Y. Deng, N. Zhang, L. Zhao, X. Yu, X. Ji, W. Liu, S. Guo, K. Liu and Z. A. Zhao, “Rapid Purification of Cell En- capsulated Hydrogel Beads from Oil Phase to Aqueous Phase in a Microfluidic Device,” Lab Chip, Vol. 11, No. 23, 2011, pp. 4117-4121. doi:10.1039/c1lc20494g

[55]   Y. Morimoto, R. Tanaka and S. J. Takeuchi, “Cons- truction of 3D, Layered Skin, Microsized Tissues by Us- ing Cell Beads for Cellular Function Analysis,” Advanced Healthcare Materials, 2012. doi:10.1002/adhm.201200189

[56]   S. Dror, “Designing Cell-Compatible Hydrogels for Bio- medical Application,” Science, Vol. 336, No. 6085, 2012, pp. 1124-1128.

[57]   J. W. Nichol and A. Khademhosseini, “Modular Tissue Engineering: Engineering Biological Tissue from the Bottom up,” Soft Matter, Vol. 5, No. 7, 2009, pp. 1312- 1319. doi:10.1039/b814285h

[58]   B. G. Chung, K. H. Lee, A. Khademhosseini and S. H. Lee, “Microfluidic Fabrication of Microengineered Hydro- gels and Their Application in Tissue Engineering,” Lab Chip, Vol. 12, No. 1, 2012, pp. 45-59. doi:10.1039/c1lc20859d

[59]   Y. M. Ren, B. Yu, H. L. Cong, Y. R. Ma, Z. Z. Ma and X. Yuan, “Preparation of Monodisperse PEG Microspheres by a T-Junction Microfluidic Chip,” Advanced Materials Research, Vol. 465, No. 12, 2012, pp. 178-181. doi:10.4028/www.scientific.net/AMR.465.178

[60]   Z. H. Nie, W. Li, M. Seo, S. Q. Xu and E. Kumacheva, “Janus and Ternary Particles Generated by Microfluidic Synthesis: Design, Synthesis and Self-Assembly,” Journal of American Chemical Society, Vol. 128, No. 29, 2006, pp. 9408-9412. doi:10.1021/ja060882n

[61]   C. H. Choi, J. H. Jung, T. S. Hwang and C. S. Lee, “In Situ Microfluidic Synthesis of Monodisperse PEG Micro- spheres,” Macromolecular Research, Vol. 17, No. 3, 2009, pp. 163-167. doi:10.1007/BF03218673

[62]   G. De Geest, J. P. Urbanski, T. Thorsen, J. Demeester and S. C. De Smedt, “Synthesis of Monodisperse Biodegra- dable Microgels in Microfluidic Devices,” Langmuir, Vol. 21, No. 23, 2005, pp. 10275-10279. doi:10.1021/la051527y

[63]   D. K. Hwang, D. Dendukuri and P. S. Doyle, “Microflui- dic-Based Synthesis of Non-Spherical Magnetic Hydrogel Microparticles,” Lab Chip, Vol. 8, No. 10, 2008, pp. 1640- 1647. doi:10.1039/b805176c

[64]   C. A. Serra and Z. Chang, “Microfluidic-Assisted Synthe- sis of Polymer Particles,” Chemical Engineering & Tech- nology, Vol. 31, No. 8, 2008, pp. 1099-1115. doi:10.1002/ceat.200800219

[65]   K. W. Bong, S. C. Chapin and P. S. Doyle, “Magnetic Bar- coded Hydrogel Microparticles for Multiplexed Detec- tion,” Langmuir, Vol. 26, No. 11, 2010, pp. 8008-8014. doi:10.1021/la904903g

[66]   C. H. Chen, A. R. Abate, D. Lee, E. M. Terentjev and D. A. Weitz, “Microfluidic Assembly of Magnetic Hydrogel Particles with Uniformly Anisotropic Structure,” Advan- ced Materials, Vol. 21, No. 31, 2009, pp. 3201-3204. doi:10.1002/adma.200900499

[67]   S. Seiffert, J. Thiele, A. R. Abate and D. A. Weitz, “Smart Microgels Capsules from Macromolecular Precursors,” Journal of American Chemical Society, Vol. 132, No. 18, 2010, pp. 6606-6609. doi:10.1021/ja102156h

[68]   K. J. Lee, J. Yoon and J. Lahann, “Recent Advances with Anisotropic Particles,” Current Opinion in Colloid & Inter- face Science, Vol. 16, No. 3, 2011, pp. 195-202. doi:10.1016/j.cocis.2010.11.004

[69]   R. F. Shepherd, J. C. Conrad, S. K. Rhodes, D. R. Link, M. Marquez, D. A. Weitz and J. A. Lewis, “Microfluidic Assembly of Homogeneous and Janus Colloid-Filled Hy- drogel Granules,” Langmuir, Vol. 22, No. 21, 2006, pp. 8618-8622. doi:10.1021/la060759+

[70]   Q. Wang, D. Zhang, H. B. Xu, X. L. Yang, A. Q. Shen and Y. J. Yang, “Microfluidic One-Step Fabrication of Radiopaque Alginate Microgels with in Situ Synthesized Barium Sulfate Nanoparticles,” Lab Chip, Vol. 12, No. 22, 2012, pp. 4781-4786. doi:10.1039/c2lc40740j

[71]   S. Seiffert, M. B. Romanowsky and D. A. Weitz, “Janus Microgels Produced from Functional Precursor Poly- mers,” Langmuir, Vol. 26, No. 18, 2010, pp. 14842-14847. doi:10.1021/la101868w

[72]   C. L. Lewis, Y. Lin, C. X. Yang, A. K. Manocchi, K. P. Yuet, P. S. Doyle and H. M. Yi, “Microfluidic Fabrication of Hydrogel Microparticles Containing Functionalized Viral Nanotemplates” Langmuir, Vol. 26, No. 16, 2010, pp. 13436-13441. doi:10.1021/la102446n

[73]   D. Dendukuri, D. C. Pregibon, J. Collins, T. A. Hatton and P. S. Doyle, “Continuous-Flow Lithography for High- Throughput Microparticle Synthesis,” Nature Materials, Vol. 5, No. 5, 2006, pp. 365-369. doi.10.1038/nmat1617

[74]   G. J. M. Fechine, J. A. G. Barros and L. H. Catalani, “Poly(N-Vinyl-2-Pyrrolidone) Hydrogel Production by Ul- traviolet Radiation: New Methodologies to Accelerate Crosslinking,” Vol. 45, No. 14, Polymer, pp. 4705-4709. doi:10.1016/j.polymer.2004.05.006

[75]   S. A. Lee, S. E. Chung, W. Park, S. H. Lee and S. H. Kwon, “Three-Dimensional Fabrication of Heterogeneous Microstructures Using Soft Membrane Deformation and Opofluidic Maskless Lithography,” Lab Chip, Vol. 9, No. 12, 2009, pp. 1670-1675. doi:10.1039/b819999j

[76]   T. Rossow, J. A. Heyman, A. J. Ehrlicher, A. Langhoff, D. A. Weitz, R. Haag and S. Seiffert, “Controlled Synthesis of Cell-Laden Microgels by Radical-Free Gelation in Drop- let Microfluidics,” Journal of American Chemical Society, Vol. 134, No. 10, 2012, pp. 4983-4989. doi:10.1021/ja300460p

[77]   R. K. Shah, J. W. Kim, J. J. Agresti, D. A. Weitz and L. Y. Chu, “Fabrication of Monodisperse Thermosensitive Microgels and Gel Capsules in Microfluidic Devices,” Soft Matter, Vol. 4, No. 12, 2008, pp. 2303-2309. doi:10.1039/b808653m

[78]   L. Y. Chu, J. W. Kim, R. K. Shah and D. A. Weitz, “Mono- disperse Thermoresponsive Microgels with Tunable Vo- lume-Phase Transition Kinetics,” Advanced Functional Ma- terials, Vol. 17, No. 17, 2007, pp. 3499-3504. doi:10.1002/adfm.200700379

[79]   W. J. Duncanson, T. Lin, A. R. Abate, S. Seiffert, R. K. Shah and D. A. Weitz, “Microfluidic Synthesis of Advan- ced Microparticles for Encapsulation and Controlled Re- lease,” Lab Chip, Vol. 12, No. 12, 2012, pp. 2135-2145. doi:10.1039/c2lc21164e

[80]   N. Raz, J. K. Li, L. K. Fiddes, E. Tumarkin, G. C. Walker and E. Kumacheva, “Microgels with an Interpenetrating Network Structure as a Model System for Cell Studies,” Macromolecules, Vol. 43, No. 17, 2010, pp. 7277-7281. doi:10.1021/ma101231z

[81]   P. Roca-Cusachs, I. Almendros, R. Sunyer, N. Gavara, R. Farre and D. Navajas, “Rheology of Passive and Adhe- sion-Activated Neutrophils Probed by Atomic Force Mi- croscopy,” Biophysical Journal, Vol. 91, No. 9, 2006, pp. 3508- 3518. doi:10.1529/biophysj.106.088831

[82]   E. P. Wojcikiewicz, X. H. Zhang, A. Chen and V. T. Moy, “Contributions of Molecular Binding Events and Cellular Compliance to the Modulation of Leukocyte Adhesion,” Journal of Cell Science, Vol. 116, No. 15, 2003, pp. 2531-2539. doi:10.1242/jcs.00465

[83]   K. Q. Jiang, C. Xue, C. Arya, C. R. Shao, E. O. George, D. L. DeVoe and S. R. Raghavan, “A New Approach to in Situ Micromanufacturing: Microfluidic Fabrication of Magnetic and Fluorescent Chains Using Chitosan Micro- particles as Building Blocks,” Small, Vol. 7, No. 17, 2011, pp. 2470-2476.

[84]   R. C. Luo, B. Neu and S. S. Venkatraman, “Surface Func- tionalization of Nanoparticles to Control Cell Interactions and Drug Release,” Small, Vol. 8, No. 16, 2012, pp. 2585- 2594. doi:10.1002/smll.201200398

[85]   R. A. A. Muzzarelli, “Genipin-Crosslinked Chitosan Hydro- gels as Biomedical and Pharmaceutical Aids,” Carbon- hydrate Polymers, Vol. 77, No. 1, 2009, pp. 1-9. doi:10.1016/j.carbpol.2009.01.016

[86]   M. Rubinstein and R. H. Colby, “Polymer Physics,” Oxford University Press, Oxford, 2003.

[87]   S. Ladet, L. David and A. Domard, “Multi-Membrane Hydrogels,” Nature, Vol. 452, No. 6, 2008, pp. 76-80. doi:10.1038/nature06619

[88]   S. Q. Xu, Z. H. 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 Us- ing Microfluidics: Control over Size, Shape and Com- position,” Angewandte Chemie International Edition, Vol. 44, No. 5, 2005, pp. 724-728. doi:10.1002/anie.200462226

[89]   S. Iwamoto, K. Nakagawa, S. Sugiura and M. Nakajima, “Preparation of Gelatin Microbeads with a Narrow Size Distribution Using Microchannel Emulsification,” AAPS PharmSciTech, Vol. 3, No. 3, 2002, pp. 72-76. doi:10.1007/BF02830623

[90]   B. Walther, C. Cramer, A. Tiemeyer, L. Hamberg, P. Fis- cher, E. J. Windhab and A. M. Hermansson, “Drop De- formation Dynamics and Gel Kinetics in a Co-Flowing Water-in-Oil System,” Journal of Colloid and Interface Science, Vol. 286, No. 1, 2005, pp. 378-386. doi:10.1016/j.jcis.2005.01.054

[91]   G. A. Di Lullo, S. M Sweeney, J. Korkko, L. Ala-Kokko and J. D. San Antonio, “Mapping the Ligand-Binding Sites and Disease-Associated Mutations on the Most Abundant Protein in the Human, Type I Collagen,” Journal of Bio- logical Chemistry, Vol. 277, No. 8, 2002, pp. 4223-4230. doi:10.1074/jbc.M110709200

[92]   Y. Morimoto, W. H. Tan and S. Takeuchi, Biomed. “Three- Dimensional Axisymmetric Flow-Focusing Device Using Stereolithography,” Microdevices, Vol. 11, No. 2, 2009, pp. 369-377. doi:10.1007/s10544-008-9243-y

[93]   S. M. Hong, H. J. Hsu, R. Kaunas and J. Kameoka, “Col- lagen Microsphere Production on a Chip,” Lab Chip, Vol. 12, No. 18, 2012, pp. 3277-3280. doi:10.1039/c2lc40558j

[94]   S. Sugiura, T. Oda, Y. Izumida, Y. Aoyagi, M. Satake, A. Ochiai, N. Ohkohchi and M. Nakajima, “Size Control of Calcium Alginate Beads Containing Living Cells Using Micro-Nozzle Array,” Biomaterials, Vol. 26, No. 16, 2005, pp. 3327-3331. doi:10.1016/j.biomaterials.2004.08.029

[95]   W. H. Tan, and S. Takeuchi, “Monodisperse Alginate Hy- drogel Microbeads for Cell Encapsulation,” Advanced Ma- terials, Vol. 19, No. 18, 2007, pp. 2696-2701. doi:10.1002/adma.200700433

[96]   H. Zhang, E. Tumarkin, R. Peerani, Z. Nie, M. A. Sullan, G. C. Walker and E. Kumacheva, “Microfluidic Produc- tion of Biopolymer Microcapsules with Controlled Mor- phology,” Journal of American Chemical Society, Vol. 128, No. 37, 2006, pp. 12205-12210. doi:10.1021/ja0635682

[97]   P. S. Dittrich and A. Manz, “Lab-on-a-Chip: Microflui- dics in Drug Discovery,” Nature Reviews Drug Discovery, Vol. 5, No. 5, 2006, pp. 210-218. doi:10.1038/nrd1985

[98]   C. H. Yang, K. S. Huang and J. Y. Chang, “Manufac- turing Monodisperse Chitosan Microparticles Containing Ampicillin Using a Microchannel Chip,” Biomedical Micro- devices, Vol. 9, No. 2, 2007, pp. 253-259. doi:10.1007/s10544-006-9029-z

[99]   C. H. Yang, K. S. Huang, Y. S. Lin, K. Lu, C. C. Tzeng, E. C. Wang, C. H. Lin, W. Y. Hsu and J. Y. Chang, “Micro- fluidic Assisted Synthesis of Multi-Functional Polycapro- lactone Microcapsules: Incorporation of CsTe Quantum Dots, Fe3O4 Superparamagnetic Nanoparticles and Tamo- xifen Anticancer Drugs,” Lab Chip, Vol. 9, No. 7, 2009, pp. 961-965. doi:10.1039/b814952f

[100]   L. Y. Chu, A. S. Utada, R. K. Shah, J. W. Kim and D. A. Weitz, “Controllable Monodisperse Multiple Emulsion,” Angewandte Chemie International Edition, Vol. 46, No. 47, 2007, pp. 8907-8974. doi:10.1002/anie.200702736

[101]   G. Karoubi, M. L. Ormiston, D. J. Stewart and D. W. Cour- tman, “Single-Cell Hydrogel Encapsulation for Enhanced Survival of Human Marrow Stromal Cells,” Biomaterials, Vol. 30, No. 29, 2009, pp. 5445-5455. doi:10.1016/j.biomaterials.2009.06.035

[102]   J. F. Edd, D. Di Carlo, K. J. Humphry, S. Koster, D. Irimia, D. A. Weitz and M. Toner, “Controlled Encapsu- lation of Single-Cells into Monodisperse Picolitre Drops,” Lab Chip, Vol. 8, No. 8, 2008, pp. 1262-1264. doi:10.1039/b805456h

[103]   E. Tumarkin, L. Tzadu, E. Csaszar, M. Seo, H. Zhang, A. Lee, R. Peerani, K. Purpura, P. W. Zandstra and E. Kuma- cheva, “High-Throughput Combinatorial Cell Co-Culture Using Microfluidics,” Integrative Biology, Vol. 3, No. 6, 2011, pp. 653-662. doi:10.1039/c1ib00002k

[104]   B. M. Leung and M. V. Sefton, “A Modular Approach to Cardiac Tissue Engineering,” Tissue Engineering Part A, 2010, Vol. 16, No. 10, pp. 3207-3218. doi:10.1089/ten.tea.2009.0746

[105]   D. A. Bruzewicz, A. P. McGuigan and G. M. Whitesides, “Fabrication of a Modular Tissue Construct in a Micro- fluidic Chip,” Lab Chip, Vol. 8, No. 5, 2008, pp. 663-671. doi:10.1039/b719806j

[106]   C. C. Wang, K. C. Yang, K. H. Lin, H. C. Liu and F. H. Lin, “A Highly Organized Three-Dimensional Alginate Scaffold for Cartilage Tissue Engineering Prepared by Microfluidic Technology,” Biomaterials, Vol. 32, No. 29, 2011, pp. 7118-7126. doi:10.1016/j.biomaterials.2011.06.018

[107]   J. Lee, M. J. Cuddihy, G. M. Cater and N. A. Kotov, “Engineering Liver Tissue Spheroids with Inverted Col- loidal Crystal Scaffolds,” Biomaterials, Vol. 30, No. 27, 2009, pp. 4687-4694. http://dx.doi:10.1016/j.biomaterials.2009.05.024

[108]   C. S. Liu, J. J. Liu, D. Gao M. Y. Ding and J. M. Lin, “Fabrication of Microwell Arrays Based on Two-Dimen- tional Ordered Polystyrene Microspheres for High-Through- put Single-Cell Analysis,” Analytical Chemistry, Vol. 82, No. 22, 2010, pp. 9418-9424. doi:10.1021/ac102094r

[109]   C. Y. Li, D. K. Wood, C. M. Hsu and S. N. Bhatia, “DNA- Templated Assembly of Droplet-Derived PEG Micro- tissues,” Lab Chip, Vol. 11, No. 17, 2011, pp. 2967-2975. doi:10.1039/c1lc20318e

[110]   Y. T. Matsunaga, Y. Morimoto and S. J. Takeuchi, “Mold- ing Cell Beads for Rapid Construction of Macroscopic 3D Tissue Architecture,” Advanced Healthcare Materials, Vol. 23, No. 3, 2011, pp. H90-H94.

[111]   N. K. Bawolin, M. G. Li, X. B. Chen and W. J. Zhang, “Modeling Material-Degradation-Induced Elastic Property of Tissue Engineering Scaffolds,” Journal of Biomechanical Engineering, Vol. 132, No. 11, 2010, pp. 111001-111008. doi:10.1115/1.4002551

 
 
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