Abstract
Microfluidics affords precise control over the flow of multiphasic fluids in micron-scale channels. By manipulating the viscous and surface tension forces present in multiphasic flows in microfluidic channels, it is possible to produce highly uniform emulsion droplets one at a time. Monodisperse droplets generated based on microfluidics are useful templates for producing uniform microcapsules and microparticles for encapsulation and delivery of active ingredients as well as living cells. Also, droplet microfluidics have been extensively exploited as a means to enable highthroughput biological screening and assays. Despite the promise droplet-based microfluidics hold for a wide range of applications, low production rate (<<10mL/hour) of emulsion droplets has been a major hindrance to widespread utilization at the industrial and commercial scale. Several reports have recently shown that one way to overcome this challenge and enable mass production of microfluidic droplets is to parallelize droplet generation, by incorporating a large number of droplet generation units (N>>100) and networks of fluid channels that distribute fluid to each of these generators onto a single chip. To parallelize droplet generation and, at the same time, maintain high uniformity of emulsion droplets, several considerations have to be made including the design of channel geometries to ensure even distribution of fluids to each droplet generator, methods for large-scale and uniform fabrication of microchannels, device materials for mechanically robust operation to withstand high-pressure injection, and development of commercially feasible fabrication techniques for three-dimensional microfluidic devices. We highlight some of the recent advances in the mass production of highly uniform microfluidics droplets via parallelization and discuss outstanding issues.
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References
Y. Kikuchi, K. Sato, H. Ohki and T. Kaneko, Microvasc. Res., 44, 226 (1992).
A. Manz, D. J. Harrison, E.M. J. Verpoorte, J.C. Fettinger, A. Paulus, H. Ludi and H. M. Widmer, J. Chromatogr., 593, 253 (1992).
P. Garstecki, M. J. Fuerstman, H. A. Stone and G. M. Whitesides, Lab Chip, 6, 437 (2006).
L. Mazutis and A.D. Griffiths, Lab Chip, 12, 1800 (2012).
X. C. I. Solvas and A. deMello, Chem. Commun., 47, 1936 (2011).
S. H. Jin, H. H. Jeong, B. Lee, S. S. Lee and C. S. Lee, Lab Chip, 15, 3677 (2015).
Y. Pang, H. Kim, Z. M. Liu and H. A. Stone, Lab Chip, 14, 4029 (2014).
S. Sugiura, M. Nakajima, S. Iwamoto and M. Seki, Langmuir, 17, 5562 (2001).
A. S. Utada, A. Fernandez-Nieves, H.A. Stone and D. A. Weitz, Phys. Rev. Lett., 99, 094502 (2007).
M. H. Lee, K. C. Hribar, T. Brugarolas, N. P. Kamat, J. A. Burdick and D. Lee, Adv. Funct. Mater., 22, 131 (2012).
H.N. Joensson and H.A. Svahn, Angew. Chem. Int. Ed., 51, 12176 (2012).
H. H. Jeong, S. H. Jin, B. J. Lee, T. Kim and C. S. Lee, Lab Chip, 15, 889 (2015).
S. Duraiswamy and S. A. Khan, Nano Lett., 10, 3757 (2010).
J. H. Jung, T. J. Park, S.Y. Lee and T. S. Seo, Angew. Chem. Int. Ed., 51, 5634 (2012).
B. J. Hindson, K.D. Ness, D.A. Masquelier, P. Belgrader, N. J. Heredia, A. J. Makarewicz, I. J. Bright, M.Y. Lucero, A. L. Hiddessen, T.C. Legler, T. K. Kitano, M.R. Hodel, J. F. Petersen, P.W. Wyatt, E.R. Steenblock, P. H. Shah, L. J. Bousse, C.B. Troup, J. C. Mellen, D. K. Wittmann, N. G. Erndt, T. H. Cauley, R.T. Koehler, A. P. So, S. Dube, K. A. Rose, L. Montesclaros, S. L. Wang, D.P. Stumbo, S.P. Hodges, S. Romine, F.P. Milanovich, H. E. White, J. F. Regan, G. A. Karlin-Neumann, C.M. Hindson, S. Saxonov and B.W. Colston, Anal. Chem., 83, 8604 (2011).
S. Juul, Y. P. Ho, J. Koch, F. F. Andersen, M. Stougaard, K.W. Leong and B.R. Knudsen, ACS Nano, 5, 8305 (2011).
D. Koziej, C. Floryan, R. A. Sperling, A. J. Ehrlicher, D. Issadore, R. Westervelt and D. A. Weitz, Nanoscale, 5, 5468 (2013).
J. J. Agresti, E. Antipov, A.R. Abate, K. Ahn, A. C. Rowat, J.C. Baret, M. Marquez, A. M. Klibanov, A.D. Griffiths and D. A. Weitz, Proc. Natl. Acad. Sci. U.S.A., 107, 6550 (2010).
E. Brouzes, M. Medkova, N. Savenelli, D. Marran, M. Twardowski, J. B. Hutchison, J.M. Rothberg, D. R. Link, N. Perrimon and M. L. Samuels, Proc. Natl. Acad. Sci. U.S.A., 106, 14195 (2009).
S. L. Sjostrom, Y. P. Bai, M.T. Huang, Z. H. Liu, J. Nielsen, H. N. Joensson and H. A. Svahn, Lab Chip, 14, 806 (2014).
M. Muluneh, B. Kim, G. Buchsbaum and D. Issadore, Lab Chip, 14, 4638 (2014).
V. Barbier, H. Willaime, P. Tabeling and F. Jousse, Phys. Rev. E, 74, (2006).
C. Holtze, J. Phys. D Appl. Phys., 46, (2013).
S.M. Joscelyne and G. Tragardh, J. Membrane Sci., 169, 107 (2000).
G.T. Vladisavljevic, N. Khalid, M.A. Neves, T. Kuroiwa, M. Nakajima, K. Uemura, S. Ichikawa and I. Kobayashi, Adv. Drug. Deliver. Rev., 65, 1626 (2013).
J. Lim, O. Caen, J. Vrignon, M. Konrad, V. Taly and J. C. Baret, Biomicrofluidics, 9, 034101 (2015).
S. Sahin and K. Schroen, Lab Chip, 15, 2486 (2015).
T. Nisisako, T. Ando and T. Hatsuzawa, Lab Chip, 12, 3426 (2012).
M. B. Romanowsky, A.R. Abate, A. Rotem, C. Holtze and D.A. Weitz, Lab Chip, 12, 802 (2012).
M. Muluneh and D. Issadore, Lab Chip, 13, 4750 (2013).
H. H. Jeong, V.R. Yelleswarapu, S. Yadavali, D. Issadore and D. Lee, Lab Chip, 15, 4387 (2015).
D. Bardin, M.R. Kendall, P. A. Dayton and A. P. Lee, Biomicrofluidics, 7, 034112 (2013).
W. Li, J. Greener, D. Voicu and E. Kumacheva, Lab Chip, 9, 2715 (2009).
D. Conchouso, D. Castro, S.A. Khan and I.G. Foulds, Lab Chip, 14, 3011 (2014).
G. Tetradis-Meris, D. Rossetti, C. P. de Torres, R. Cao, G. P. Lian and R. Janes, Ind. Eng. Chem. Res., 48, 8881 (2009).
J.C. McDonald and G.M. Whitesides, Acc. Chem. Res., 35, 491 (2002).
P.N. Nge, C. I. Rogers and A.T. Woolley, Chem. Rev., 113, 2550 (2013).
G. S. Fiorini and D.T. Chiu, Biotechniques, 38, 429 (2005).
T. Nisisako and T. Torii, Lab Chip, 8, 287 (2008).
Y. Xu, C. X. Wang, L. X. Li, N. Matsumoto, K. Jang, Y.Y. Dong, K. Mawatari, T. Suga and T. Kitamori, Lab Chip, 13, 1048 (2013).
J. Kotowski, V. Navratil, Z. Slouka and D. Snita, Microelectron. Eng., 110, 441 (2013).
V. Saarela, M. Haapala, R. Kostiainen, T. Kotiaho and S. Franssila, Lab Chip, 7, 644 (2007).
H.Y. Zhai, K. S. Yuan, X. Yu, Z. G. Chen, Z. P. Liu and Z. H. Su, Electrophoresis, 36, 2509 (2015).
V. Saarela, M. Haapala, R. Kostiainen, T. Kotiaho and S. Franssila, J. Micromech. Microeng., 19, 055001 (2009).
K. Kolari, V. Saarela and S. Franssila, J. Micromech. Microeng., 18, (2008).
A. Baram and M. Naftali, J. Micromech. Microeng., 16, 2287 (2006).
J. Giboz, T. Copponnex and P. Mele, J. Micromech. Microeng., 17, R96 (2007).
S. Tanzi, M. Matteucci, T. L. Christiansen, S. Friis, M.T. Christensen, J. Garnaes, S. Wilson, J. Kutchinsky and R. Taboryski, Lab Chip, 13, 4784 (2013).
P. Abgrall, L. N. Low and N.T. Nguyen, Lab Chip, 7, 520 (2007).
D. J. Guckenberger, T.E. de Groot, A.M.D. Wan, D. J. Beebe and E.W. K. Young, Lab Chip, 15, 2364 (2015).
M.B.G. Jun, X.Y. Liu, R.E. DeVor and S.G. Kapoor, J. Manuf. Sci. E-T Asme., 128, 893 (2006).
H. Becker and C. Gartner, Electrophoresis, 21, 12 (2000).
M. Heckele, A. E. Guber and R. Truckenmuller, Microsyst. Technol., 12, 1031 (2006).
C.W. Tsao and D.L. DeVoe, Microfluid. Nanofluid., 6, 1 (2009).
E. Roy, J. C. Galas and T. Veres, Lab Chip, 11, 3193 (2011).
S.C. Yoon, Z. Horita and H. S. Kim, J. Mater. Process. Tech., 201, 32 (2008).
S.C. Yoon, H. G. Jeong, S. Lee and H. S. Kim, Comp. Mater. Sci., 77, 202 (2013).
C.W. Tsao, L. Hromada, J. Liu, P. Kumar and D. L. DeVoe, Lab Chip, 7, 499 (2007).
F. Saharil, C. F. Carlborg, T. Haraldsson and W. van der Wijngaart, Lab Chip, 12, 3032 (2012).
S.K. Sia and G. M. Whitesides, Electrophoresis, 24, 3563 (2003).
W. H. Grover, A. M. Skelley, C. N. Liu, E.T. Lagally and R.A. Mathies, Sensor. Actuat. B-Chem., 89, 315 (2003).
J.W. Zhou, A.V. Ellis and N. H. Voelcker, Electrophoresis, 31, 2 (2010).
B. L. Thompson, Y.W. Ouyang, G.R. M. Duarte, E. Carrilho, S.T. Krauss and J. P. Landers, Nat. Protoc., 10, 875 (2015).
F.P.W. Melchels, J. Feijen and D.W. Grijpma, Biomaterials, 31, 6121 (2010).
A. Waldbaur, H. Rapp, K. Lange and B. E. Rapp, Anal. Methods, 3, 2681 (2011).
A. I. Shallan, P. Smejkal, M. Corban, R. M. Guijt and M. C. Breadmore, Anal. Chem., 86, 3124 (2014).
P. F. O’Neill, A. Ben Azouz, M. Vazquez, J. Liu, S. Marczak, Z. Slouka, H.C. Chang, D. Diamond and D. Brabazon, Biomicrofluidics, 8, 052112 (2014).
A.K. Au, W. Lee and A. Folch, Lab Chip, 14, 1294 (2014).
G. Comina, A. Suska and D. Filippini, Lab Chip, 14, 424 (2014).
C.M.B. Ho, S. H. Ng, K.H. H. Li and Y. J. Yoon, Lab Chip, 15, 3627 (2015).
K.C. Bhargava, B. Thompson and N. Malmstadt, Proc. Natl. Acad. Sci. U. S. A., 111, 15013 (2014).
T. Femmer, A. Jans, R. Eswein, N. Anwar, M. Moeller, M. Wessling and A. J. Kuehne, ACS Appl. Mater. Interfaces, 7, 12635 (2015).
T.M. Tran, S. Cater and A.R. Abate, Biomicrofluidics, 8, 016502 (2014).
L.R. Arriaga, E. Amstad and D. A. Weitz, Lab Chip, 15, 3335 (2015).
S.C. Kim, D. J. Sukovich and A.R. Abate, Lab Chip, 15, 3163 (2015).
T. Brugarolas, F.Q. Tu and D. Lee, Soft Matter, 9, 9046 (2013).
S. S. Datta, A. Abbaspourrad, E. Amstad, J. Fan, S. H. Kim, M. Romanowsky, H. C. Shum, B. J. Sun, A. S. Utada, M. Windbergs, S.B. Zhou and D. A. Weitz, Adv. Mater., 26, 2205 (2014).
C.X. Zhao, Adv. Drug. Deliver. Rev., 65, 1420 (2013).
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Daeyeon Lee Daeyeon Lee received his B.S. in Chemical Engineering from Seoul National University in 2001 and received his Ph.D. in Chemical Engineering at MIT in 2007. After his postdoctoral fellowship at Harvard University, Daeyeon joined the University of Pennsylvania in 2009 and is currently Professor of Chemical and Biomolecular Engineering. Daeyeon’s research interests include structure-property relationship of nanoparticle assemblies, interfacial behavior of Janus particles, and microfluidic fabrication of functional structures. Daeyeon has won numerous awards including the 2010 Victor K. LaMer Award, NSF CAREER Award, 2012 KIChE President Young Investigator Award, 2013 3M Nontenured Faculty Award, 2013 AIChE NSEF Young Investigator Award and 2014 Unilever Award for Young Investigator in Colloid and Surface Science.
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Jeong, HH., Issadore, D. & Lee, D. Recent developments in scale-up of microfluidic emulsion generation via parallelization. Korean J. Chem. Eng. 33, 1757–1766 (2016). https://doi.org/10.1007/s11814-016-0041-6
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DOI: https://doi.org/10.1007/s11814-016-0041-6