Skip to main content
SpringerLink
Log in

Microfluidic Micro/Nano Droplets

  • Chapter
Springer Handbook of Nanotechnology

Part of the book series: Springer Handbooks ((SHB))

  • 10k Accesses

Abstract

Microfluidic droplet technology has evolved rapidly since the first microfluidic droplet generator was reported over a decade ago. It has subsequently branched out and emerged as a practical solution to enhance the capabilities of many other fields, including, but not limited to: high-throughput screening, biosensing, drug delivery and synthetic biology. In this chapter, we will report on recent advancements in droplet microfluidic technologies that have emerged since Teh et al.'s comprehensive 2007 review. We begin with a brief history of droplet microfluidics and introduce methods of droplet production, manipulation, and sensing methodologies. The remainder of the chapter is dedicated to design considerations for various droplet production configurations, concluding with a discussion on applications, trends and the general direction that the field is headed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. G.M. Whitesides: The origins and the future of microfluidics, Nature 442(7101), 368–373 (2006)

    Article  Google Scholar 

  2. T. Thorsen, S.J. Maerkl, S.R. Quake: Microfluidic large-scale integration, Science 298(5593), 580–584 (2002)

    Article  Google Scholar 

  3. J. Melin, S.R. Quake: Microfluidic large-scale integration: The evolution of design rules for biological automation, Annu. Rev. Biophys. Biomol. Struct. 36(1), 213–231 (2007)

    Article  Google Scholar 

  4. H. Song, D.L. Chen, R.F. Ismagilov: Reactions in droplets in microfluidic channels, Angew. Chem. Int. Ed. 45(44), 7336–7356 (2006)

    Article  Google Scholar 

  5. T. Thorsen, R.W. Roberts, F.H. Arnold, S.R. Quake: Dynamic pattern formation in a vesicle-generating microfluidic device, Phys. Rev. Lett. 86(18), 4163–4166 (2001)

    Article  Google Scholar 

  6. B. Zheng, J.D. Tice, R.F. Ismagilov: Formation of droplets of alternating composition in microfluidic channels and applications to indexing of concentrations in droplet-based assays, Anal. Chem. 76(17), 4977–4982 (2004)

    Article  Google Scholar 

  7. S.L. Anna, N. Bontoux, H.A. Stone: Formation of dispersions using flow focusing in microchannels, Appl. Phys. Lett. 82(3), 364 (2003)

    Article  Google Scholar 

  8. J. Shim, R.T. Ranasinghe, C.A. Smith, S.M. Ibrahim, F. Hollfelder, W.T.S. Huck, D. Klenerman, C. Abell: Ultrarapid generation of femtoliter microfluidic droplets for single-molecule-counting immunoassays, ACS Nano 7(7), 5955–5964 (2013)

    Article  Google Scholar 

  9. H.-H. Jeong, V.R. Yelleswarapu, S. Yadavali, D. Issadore, D. Lee: Kilo-scale droplet generation in three-dimensional monolithic elastomer device (3-D MED), Lab. Chip 15(23), 4387–4392 (2015)

    Article  Google Scholar 

  10. Y. Xia, G.M. Whitesides: Soft lithography, Annu. Rev. Mater. Sci. 28(1), 153–184 (1998)

    Article  Google Scholar 

  11. Y.-C. Tan, J.S. Fisher, A.I. Lee, V. Cristini, A.P. Lee: Design of microfluidic channel geometries for the control of droplet volume, chemical concentration, and sorting, Lab. Chip 4(4), 292 (2004)

    Article  Google Scholar 

  12. X. Niu, S. Gulati, J.B. Edel, A.J. deMello: Pillar-induced droplet merging in microfluidic circuits, Lab. Chip 8(11), 1837 (2008)

    Article  Google Scholar 

  13. P. Singh, N. Aubry: Transport and deformation of droplets in a microdevice using dielectrophoresis, Electrophoresis 28(4), 644–657 (2007)

    Article  Google Scholar 

  14. C. Priest, S. Herminghaus, R. Seemann: Controlled electrocoalescence in microfluidics: Targeting a single lamella, Appl. Phys. Lett. 89(13), 134101 (2006)

    Article  Google Scholar 

  15. J. Köhler, T. Henkel, A. Grodrian, T. Kirner, M. Roth, K. Martin, J. Metze: Digital reaction technology by micro segmented flow–components, concepts and applications, Chem. Eng. J. 101(1–3), 201–216 (2004)

    Article  Google Scholar 

  16. R.M. Lorenz, J.S. Edgar, G.D.M. Jeffries, D.T. Chiu: Microfluidic and optical systems for the on-demand generation and manipulation of single femtoliter-volume aqueous droplets, Anal. Chem. 78(18), 6433–6439 (2006)

    Article  Google Scholar 

  17. D. Link, S. Anna, D. Weitz, H. Stone: Geometrically mediated breakup of drops in microfluidic devices, Phys. Rev. Lett. (2004) doi:10.1103/PhysRevLett.92.054503

  18. D.N. Adamson, D. Mustafi, J.X.J. Zhang, B. Zheng, R.F. Ismagilov: Production of arrays of chemically distinct nanolitre plugs via repeated splitting in microfluidic devices, Lab. Chip 6(9), 1178 (2006)

    Article  Google Scholar 

  19. S.K. Cho, H. Moon, C.-J. Kim: Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits, J. Microelectromech. Syst. 12(1), 70–80 (2003)

    Article  Google Scholar 

  20. J.J. Agresti, E. Antipov, A.R. Abate, K. Ahn, A.C. Rowat, J.-C. Baret, M. Marquez, A.M. Klibanov, A.D. Griffiths, D.A. Weitz: Ultrahigh-throughput screening in drop-based microfluidics for directed evolution, Proc. Natl. Acad. Sci. 107(9), 4004–4009 (2010)

    Article  Google Scholar 

  21. J. Lim, P. Gruner, M. Konrad, J.-C. Baret: Micro-optical lens array for fluorescence detection in droplet-based microfluidics, Lab. Chip 13(8), 1472 (2013)

    Article  Google Scholar 

  22. M. Kim, M. Pan, Y. Gai, S. Pang, C. Han, C. Yang, S.K.Y. Tang: Optofluidic ultrahigh-throughput detection of fluorescent drops, Lab. Chip 15(6), 1417–1423 (2015)

    Article  Google Scholar 

  23. D.-K. Kang, M.M. Ali, K. Zhang, S.S. Huang, E. Peterson, M.A. Digman, E. Gratton, W. Zhao: Rapid detection of single bacteria in unprocessed blood using integrated comprehensive droplet digital detection, Nat. Commun. 5, 5427 (2014)

    Article  Google Scholar 

  24. S. Liu, Y. Gu, R.B. Le Roux, S.M. Matthews, D. Bratton, K. Yunus, A.C. Fisher, W.T.S. Huck: The electrochemical detection of droplets in microfluidic devices, Lab. Chip 8(11), 1937 (2008)

    Article  Google Scholar 

  25. L.M. Fidalgo, G. Whyte, B.T. Ruotolo, J.L.P. Benesch, F. Stengel, C. Abell, C.V. Robinson, W.T.S. Huck: Coupling microdroplet microreactors with mass spectrometry: Reading the contents of single droplets online, Angew. Chem. Int. Ed. 48(20), 3665–3668 (2009)

    Article  Google Scholar 

  26. X.Z. Niu, B. Zhang, R.T. Marszalek, O. Ces, J.B. Edel, D.R. Klug, A.J. deMello: Droplet-based compartmentalization of chemically separated components in two-dimensional separations, Chem. Commun. (2009) doi:10.1039/b918100h

  27. M.P. Cecchini, J. Hong, C. Lim, J. Choo, T. Albrecht, A.J. deMello, J.B. Edel: Ultrafast surface enhanced resonance raman scattering detection in droplet-based microfluidic systems, Anal. Chem. 83(8), 3076–3081 (2011)

    Article  Google Scholar 

  28. Y.-C. Tan, Y.L. Ho, A.P. Lee: Microfluidic sorting of droplets by size, Microfluid. Nanofluidics 4(4), 343–348 (2007)

    Article  Google Scholar 

  29. M. Chabert, J.-L. Viovy: Microfluidic high-throughput encapsulation and hydrodynamic self-sorting of single cells, Proc. Natl. Acad. Sci. 105(9), 3191–3196 (2008)

    Article  Google Scholar 

  30. H.N. Joensson, M. Uhlén, H.A. Svahn: Droplet size based separation by deterministic lateral displacement–separating droplets by cell-induced shrinking, Lab. Chip 11(7), 1305 (2011)

    Article  Google Scholar 

  31. A.C. Hatch, A. Patel, N.R. Beer, A.P. Lee: Passive droplet sorting using viscoelastic flow focusing, Lab. Chip 13(7), 1308 (2013)

    Article  Google Scholar 

  32. J.-C. Baret, O.J. Miller, V. Taly, M. Ryckelynck, A. El-Harrak, L. Frenz, C. Rick, M.L. Samuels, J.B. Hutchison, J.J. Agresti, D.R. Link, D.A. Weitz, A.D. Griffiths: Fluorescence-activated droplet sorting (FADS): Efficient microfluidic cell sorting based on enzymatic activity, Lab. Chip 9(13), 1850 (2009)

    Article  Google Scholar 

  33. K. Ahn, C. Kerbage, T.P. Hunt, R.M. Westervelt, D.R. Link, D.A. Weitz: Dielectrophoretic manipulation of drops for high-speed microfluidic sorting devices, Appl. Phys. Lett. 88(2), 24104 (2006)

    Article  Google Scholar 

  34. T. Franke, A.R. Abate, D.A. Weitz, A. Wixforth: Surface acoustic wave (SAW) directed droplet flow in microfluidics for PDMS devices, Lab. Chip 9(18), 2625 (2009)

    Article  Google Scholar 

  35. A.R. Abate, J.J. Agresti, D.A. Weitz: Microfluidic sorting with high-speed single-layer membrane valves, Appl. Phys. Lett. 96(20), 203509 (2010)

    Article  Google Scholar 

  36. C.N. Baroud, M.R. de Saint Vincent, J.-P. Delville: An optical toolbox for total control of droplet microfluidics, Lab. Chip 7(8), 1029 (2007)

    Article  Google Scholar 

  37. S.-Y. Teh, R. Lin, L.-H. Hung, A.P. Lee: Droplet microfluidics, Lab. Chip 8(2), 198 (2008)

    Article  Google Scholar 

  38. G.F. Christopher, S.L. Anna: Microfluidic methods for generating continuous droplet streams, J. Phys. Appl. Phys. 40(19), R319–R336 (2007)

    Article  Google Scholar 

  39. M. Baker: Digital PCR hits its stride, Nat. Methods 9(6), 541–544 (2012)

    Article  Google Scholar 

  40. A.R. Abate, T. Hung, R.A. Sperling, P. Mary, A. Rotem, J.J. Agresti, M.A. Weiner, D.A. Weitz: DNA sequence analysis with droplet-based microfluidics, Lab. Chip 13(24), 4864 (2013)

    Article  Google Scholar 

  41. S. Abalde-Cela, A. Gould, X. Liu, E. Kazamia, A.G. Smith, C. Abell: High-throughput detection of ethanol-producing cyanobacteria in a microdroplet platform, J. R. Soc. Interface 12(106), 20150216–20150216 (2015)

    Article  Google Scholar 

  42. P.S. Dittrich, A. Manz: Lab-on-a-chip: Microfluidics in drug discovery, Nat. Rev. Drug Discov. 5(3), 210–218 (2006)

    Article  Google Scholar 

  43. E. Brouzes, M. Medkova, N. Savenelli, D. Marran, M. Twardowski, J.B. Hutchison, J.M. Rothberg, D.R. Link, N. Perrimon, M.L. Samuels: Droplet microfluidic technology for single-cell high-throughput screening, Proc. Natl. Acad. Sci. 106(34), 14195–14200 (2009)

    Article  Google Scholar 

  44. A.C. Larsen, M.R. Dunn, A. Hatch, S.P. Sau, C. Youngbull, J.C. Chaput: A general strategy for expanding polymerase function by droplet microfluidics, Nat. Commun. 7, 11235 (2016)

    Article  Google Scholar 

  45. P.B. Umbanhowar, V. Prasad, D.A. Weitz: Monodisperse emulsion generation via drop break off in a coflowing stream, Langmuir 16(2), 347–351 (2000)

    Article  Google Scholar 

  46. C. Cramer, P. Fischer, E.J. Windhab: Drop formation in a co-flowing ambient fluid, Chem. Eng. Sci. 59(15), 3045–3058 (2004)

    Article  Google Scholar 

  47. G.F. Christopher, N.N. Noharuddin, J.A. Taylor, S.L. Anna: Experimental observations of the squeezing-to-dripping transition in T-shaped microfluidic junctions, Phys. Rev. E 78(3), 36317 (2008)

    Article  Google Scholar 

  48. J. Husny, J.J. Cooper-White: The effect of elasticity on drop creation in T-shaped microchannels, J. Non-Newton. Fluid Mech. 137(1–3), 121–136 (2006)

    Article  Google Scholar 

  49. J. Xu, G. Luo, G. Chen, J. Wang: Experimental and theoretical approaches on droplet formation from a micrometer screen hole, J. Membr. Sci. 266(1–2), 121–131 (2005)

    Article  Google Scholar 

  50. J.D. Tice, A.D. Lyon, R.F. Ismagilov: Effects of viscosity on droplet formation and mixing in microfluidic channels, Anal. Chim. Acta 507(1), 73–77 (2004)

    Article  Google Scholar 

  51. P. Garstecki, H. Stone, G. Whitesides: Mechanism for flow-rate controlled breakup in confined geometries: A route to monodisperse emulsions, Phys. Rev. Lett. (2005) doi:10.1103/PhysRevLett.94.164501

  52. P. Garstecki, M.J. Fuerstman, H.A. Stone, G.M. Whitesides: Formation of droplets and bubbles in a microfluidic T-junction–scaling and mechanism of break-up, Lab. Chip 6(3), 437 (2006)

    Article  Google Scholar 

  53. S.L. Anna, H.C. Mayer: Microscale tipstreaming in a microfluidic flow focusing device, Phys. Fluids 18(12), 121512 (2006)

    Article  Google Scholar 

  54. A.S. Utada: Monodisperse double emulsions generated from a microcapillary device, Science 308(5721), 537–541 (2005)

    Article  Google Scholar 

  55. T. Ward, M. Faivre, M. Abkarian, H.A. Stone: Microfluidic flow focusing: Drop size and scaling in pressureversus flow-rate-driven pumping, Electrophoresis 26(19), 3716–3724 (2005)

    Article  Google Scholar 

  56. C. Zhou, P. Yue, J.J. Feng: Formation of simple and compound drops in microfluidic devices, Phys. Fluids 18(9), 92105 (2006)

    Article  Google Scholar 

  57. B. Beulen, J. de Jong, H. Reinten, M. van den Berg, H. Wijshoff, R. van Dongen: Flows on the nozzle plate of an inkjet printhead, Exp. Fluids 42(2), 217–224 (2007)

    Article  Google Scholar 

  58. H. Willaime, V. Barbier, L. Kloul, S. Maine, P. Tabeling: Arnold tongues in a microfluidic drop emitter, Phys. Rev. Lett. (2006) doi:10.1103/PhysRevLett.96.054501

  59. O. Ozen, N. Aubry, D.T. Papageorgiou, P.G. Petropoulos: Monodisperse drop formation in square microchannels, Phys. Rev. Lett. (2006) doi:10.1103/PhysRevLett.96.144501

  60. D.T. Chiu, R.M. Lorenz, G.D.M. Jeffries: Droplets for ultrasmall-volume analysis, Anal. Chem. 81(13), 5111–5118 (2009) doi:10.1021/ac900306q

    Article  Google Scholar 

  61. A. Huebner, S. Sharma, M. Srisa-Art, F. Hollfelder, J.B. Edel, A.J. deMello: Microdroplets: A sea of applications?, Lab. Chip 8(8), 1244 (2008)

    Article  Google Scholar 

  62. A.K. Price, B.M. Paegel: Discovery in droplets, Anal. Chem. 88(1), 339–353 (2016)

    Article  Google Scholar 

  63. I. Shestopalov, J.D. Tice, R.F. Ismagilov: Multi-step synthesis of nanoparticles performed on millisecond time scale in a microfluidic droplet-based system, Lab. Chip 4(4), 316 (2004)

    Article  Google Scholar 

  64. V. Noireaux, A. Libchaber: A vesicle bioreactor as a step toward an artificial cell assembly, Proc. Natl. Acad. Sci. 101(51), 17669–17674 (2004)

    Article  Google Scholar 

  65. B. Ahmed, D. Barrow, T. Wirth: Enhancement of reaction rates by segmented fluid flow in capillary scale reactors, Adv. Synth. Catal. 348(9), 1043–1048 (2006)

    Article  Google Scholar 

  66. J.R. Burns, C. Ramshaw: The intensification of rapid reactions in multiphase systems using slug flow in capillaries, Lab. Chip 1(1), 10 (2001)

    Article  Google Scholar 

  67. K.-I. Sotowa, K. Irie, T. Fukumori, K. Kusakabe, S. Sugiyama: Droplet formation by the collision of two aqueous solutions in a microchannel and application to particle synthesis, Chem. Eng. Technol. 30(3), 383–388 (2007)

    Article  Google Scholar 

  68. H. Song, H.-W. Li, M.S. Munson, T.G. Van Ha, R.F. Ismagilov: On-chip titration of an anticoagulant argatroban and determination of the clotting time within whole blood or plasma using a plug-based microfluidic system, Anal. Chem. 78(14), 4839–4849 (2006)

    Article  Google Scholar 

  69. Z.T. Cygan, J.T. Cabral, K.L. Beers, E.J. Amis: Microfluidic platform for the generation of organic-phase microreactors, Langmuir 21(8), 3629–3634 (2005)

    Article  Google Scholar 

  70. A. Huebner, M. Srisa-Art, D. Holt, C. Abell, F. Hollfelder, A.J. deMello, J.B. Edel: Quantitative detection of protein expression in single cells using droplet microfluidics, Chem. Commun. (2007) doi:10.1039/b618570c

  71. M.S. Long, C.D. Jones, M.R. Helfrich, L.K. Mangeney-Slavin, C.D. Keating: Dynamic microcompartmentation in synthetic cells, Proc. Natl. Acad. Sci. 102(17), 5920–5925 (2005)

    Article  Google Scholar 

  72. V. Taly, D. Pekin, A.E. Abed, P. Laurent-Puig: Detecting biomarkers with microdroplet technology, Trends Mol. Med. 18(7), 405–416 (2012)

    Article  Google Scholar 

  73. W. Wang, Z.-X. Li, R. Luo, S.-H. Lü, A.-D. Xu, Y.-J. Yang: Droplet-based micro oscillating-flow PCR chip, J. Micromech. Microeng. 15(8), 1369–1377 (2005)

    Article  Google Scholar 

  74. 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. 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, B.W. Colston: High-throughput droplet digital PCR system for absolute quantitation of DNA copy number, Anal. Chem. 83(22), 8604–8610 (2011)

    Article  Google Scholar 

  75. T. Hatakeyama, D.L. Chen, R.F. Ismagilov: Microgram-scale testing of reaction conditions in solution using nanoliter plugs in microfluidics with detection by MALDI-MS, J. Am. Chem. Soc. 128(8), 2518–2519 (2006)

    Article  Google Scholar 

  76. A.R. Wheeler, H. Moon, C.A. Bird, R.R.O. Loo, C.-J. Kim, J.A. Loo, R.L. Garrell: Digital microfluidics with in-line sample purification for proteomics analyses with MALDI-MS, Anal. Chem. 77(2), 534–540 (2005)

    Article  Google Scholar 

  77. B.T.C. Lau, C.A. Baitz, X.P. Dong, C.L. Hansen: A complete microfluidic screening platform for rational protein crystallization, J. Am. Chem. Soc. 129(3), 454–455 (2007)

    Article  Google Scholar 

  78. H. Song, R.F. Ismagilov: Millisecond kinetics on a microfluidic chip using nanoliters of reagents, J. Am. Chem. Soc. 125(47), 14613–14619 (2003)

    Article  Google Scholar 

  79. B. Kintses, C. Hein, M.F. Mohamed, M. Fischlechner, F. Courtois, C. Lainé, F. Hollfelder: Picoliter cell lysate assays in microfluidic droplet compartments for directed enzyme evolution, Chem. Biol. 19(8), 1001–1009 (2012)

    Article  Google Scholar 

  80. D.J. Eastburn, A. Sciambi, A.R. Abate: Ultrahigh-throughput mammalian single-cell reverse-transcriptase polymerase chain reaction in microfluidic drops, Anal. Chem. 85(16), 8016–8021 (2013)

    Article  Google Scholar 

  81. E.Z. Macosko, A. Basu, R. Satija, J. Nemesh, K. Shekhar, M. Goldman, I. Tirosh, A.R. Bialas, N. Kamitaki, E.M. Martersteck, J.J. Trombetta, D.A. Weitz, J.R. Sanes, A.K. Shalek, A. Regev, S.A. McCarroll: Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets, Cell 161(5), 1202–1214 (2015)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Biomedical Engineering, University of California Irvine, 3120 Natural Sciences II, CA 92697-2715, Irvine, USA

    Gopakumar Kamalakshakurup & Derek Vallejo

  2. Dept. of Biomedical Engineering, University of California Irvine, 3120 Natural Sciences II, CA 92697, Irvine, USA

    Abraham Lee

Authors
  1. Gopakumar Kamalakshakurup
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Derek Vallejo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abraham Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Bharat Bhushan

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer-Verlag GmbH Germany

About this chapter

Cite this chapter

Kamalakshakurup, G., Vallejo, D., Lee, A. (2017). Microfluidic Micro/Nano Droplets. In: Bhushan, B. (eds) Springer Handbook of Nanotechnology. Springer Handbooks. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-54357-3_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-54357-3_17

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-54355-9

  • Online ISBN: 978-3-662-54357-3

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation