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Abstract

Recent years have witnessed an increased use of droplet-based microfluidic techniques in a wide variety of chemical and biological assays. Nevertheless, obtaining dynamic data from these platforms has remained challenging, as this often requires reading the same droplets (possibly thousands of them) multiple times over a wide range of intervals (from milliseconds to hours). In this review, we introduce the elemental techniques for the formation and manipulation of microfluidic droplets, together with the most recent developments in these areas. We then discuss a wide range of analytical methods that have been successfully adapted for analyte detection in droplets. Finally, we highlight a diversity of studies where droplet-based microfluidic strategies have enabled the characterization of dynamic systems that would otherwise have remained unexplorable.

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2017-06-12
2024-06-25
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Literature Cited

  1. Peercy PS. 1.  2000. The drive to miniaturization. Nature 406:67991023–26 [Google Scholar]
  2. Kilby JS. 2.  1964. Miniaturized electronic circuits US Patent No. 3138743 [Google Scholar]
  3. Sackmann EK, Fulton AL, Beebe DJ. 3.  2014. The present and future role of microfluidics in biomedical research. Nature 507:7491181–89 [Google Scholar]
  4. Squires TM, Quake SR. 4.  2005. Microfluidics: fluid physics at the nanoliter scale. Rev. Mod. Phys. 77:3977–1026 [Google Scholar]
  5. Whitesides GM. 5.  2006. The origins and the future of microfluidics. Nature 442:7101368–73 [Google Scholar]
  6. DeMello AJ. 6.  2006. Control and detection of chemical reactions in microfluidic systems. Nature 442:7101394–402 [Google Scholar]
  7. Krishnadasan S, Brown RJC, deMello AJ, deMello JC. 7.  2007. Intelligent routes to the controlled synthesis of nanoparticles. Lab Chip 7:111434–41 [Google Scholar]
  8. Kintses B, van Vliet LD, Devenish SRA, Hollfelder F. 8.  2010. Microfluidic droplets: new integrated workflows for biological experiments. Curr. Opin. Chem. Biol. 14:5548–55 [Google Scholar]
  9. Guo MT, Rotem A, Heyman JA, Weitz DA. 9.  2012. Droplet microfluidics for high-throughput biological assays. Lab Chip 12:122146–55 [Google Scholar]
  10. Christopher GF, Anna SL. 10.  2007. Microfluidic methods for generating continuous droplet streams. J. Phys. D Appl. Phys. 40:R319 [Google Scholar]
  11. Teh S-Y, Lin R, Hung L-H, Lee AP. 11.  2008. Droplet microfluidics. Lab Chip 8:198–220 [Google Scholar]
  12. Lagus TP, Edd JF. 12.  2013. A review of the theory, methods and recent applications of high-throughput single-cell droplet microfluidics. J. Phys. D Appl. Phys. 46:114005 [Google Scholar]
  13. Zhua Y, Fang Q. 13.  2013. Analytical detection techniques for droplet microfluidics—a review. Anal. Chim. Acta 787:24–35 [Google Scholar]
  14. Joensson HN, Svahn HA. 14.  2012. Droplet microfluidics—a tool for single-cell analysis. Angew. Chem. Int. Ed. 51:12176–92 [Google Scholar]
  15. Price AK, Paegel BM. 15.  2015. Discovery in droplets. Anal. Chem. 88:339–53 [Google Scholar]
  16. Collins DJ, Neild A, deMello A, Liu AQ, Ai Y. 16.  2015. The Poisson distribution and beyond: methods for microfluidic droplet production and single cell encapsulation. Lab Chip 15:173439–59 [Google Scholar]
  17. Thorsen T, Roberts RW, Arnold FH, Quake SR. 17.  2001. Dynamic pattern formation in a vesicle-generating microfluidic device. Phys. Rev. Lett. 86:184163–66 [Google Scholar]
  18. Anna SL, Bontoux N, Stone HA. 18.  2003. Formation of dispersions using “flow focusing” in microchannels. Appl. Phys. Lett. 82:3364–66 [Google Scholar]
  19. Umbanhowar PB, Prasad V, Weitz DA. 19.  2000. Monodisperse emulsion generation via drop break off in a coflowing stream. Langmuir 16:2347–51 [Google Scholar]
  20. Ding Y, i Solvas XC, deMello A. 20.  2015. “V-junction”: a novel structure for high-speed generation of bespoke droplet flows. Analyst 140:2414–21 [Google Scholar]
  21. Hong J, Choi M, Edel JB, deMello AJ. 21.  2010. Passive self-synchronized two-droplet generation. Lab Chip 10:202702–9 [Google Scholar]
  22. Sugiura S, Nakajima M, Iwamoto S, Seki M. 22.  2001. Interfacial tension driven monodispersed droplet formation from microfabricated channel array. Langmuir 17:185562–66 [Google Scholar]
  23. Dangla R, Kayi SC, Baroud CN. 23.  2013. Droplet microfluidics driven by gradients of confinement. PNAS 110:3853–58 [Google Scholar]
  24. Shim JU, Ranasinghe RT, Smith CA, Ibrahim SM, Hollfelder F. 24.  et al. 2013. Ultrarapid generation of femtoliter microfluidic droplets for single-molecule-counting immunoassays. ACS Nano 7:75955–64 [Google Scholar]
  25. Mittal N, Cohen C, Bibette J, Bremond N. 25.  2014. Dynamics of step-emulsification: from a single to a collection of emulsion droplet generators. Phys. Fluids 26:8082109 [Google Scholar]
  26. Hess D, Rane A, deMello AJ, Stavrakis S. 26.  2015. High-throughput, quantitative enzyme kinetic analysis in microdroplets using stroboscopic epifluorescence imaging. Anal. Chem. 87:94965–72 [Google Scholar]
  27. Zheng B, Ismagilov RF. 27.  2005. A microfluidic approach for screening submicroliter volumes against multiple reagents by using preformed arrays of nanoliter plugs in a three-phase liquid/liquid/gas flow. Angew. Chem. Int. Ed. 44:172520–23 [Google Scholar]
  28. Holtze C, Rowat AC, Agresti JJ, Hutchison JB, Angile FE. 28.  et al. 2008. Biocompatible surfactants for water-in-fluorocarbon emulsions. Lab Chip 8:101632–39 [Google Scholar]
  29. Baret JC. 29.  2012. Surfactants in droplet-based microfluidics. Lab Chip 12:3422–33 [Google Scholar]
  30. Shui LL, van den Berg A, Eijkel JCT. 30.  2009. Interfacial tension controlled W/O and O/W 2-phase flows in microchannel. Lab Chip 9:6795–801 [Google Scholar]
  31. Giaever I, Keese CR. 31.  1983. Behavior of cells at fluid interfaces. PNAS 80:1219–22 [Google Scholar]
  32. Wagner O, Thiele J, Weinhart M, Mazutis L, Weitz DA. 32.  et al. 2016. Biocompatible fluorinated polyglycerols for droplet microfluidics as an alternative to PEG-based copolymer surfactants. Lab Chip 16:165–69 [Google Scholar]
  33. Gruner P, Riechers B, Orellana LAC, Brosseau Q, Maes F. 33.  et al. 2015. Stabilisers for water-in-fluorinated-oil dispersions: key properties for microfluidic applications. Curr. Opin. Colloid Interface Sci. 20:3183–91 [Google Scholar]
  34. Gruner P, Riechers B, Semin B, Lim J, Johnston A. 34.  et al. 2016. Controlling molecular transport in minimal emulsions. Nat. Commun. 7:10392 [Google Scholar]
  35. Pan M, Rosenfeld L, Kim M, Xu MQ, Lin E. 35.  et al. 2014. Fluorinated Pickering emulsions impede interfacial transport and form rigid interface for the growth of anchorage-dependent cells. ACS Appl. Mater. Interface 6:2321446–53 [Google Scholar]
  36. Labrot V, Schindler M, Guillot P, Colin A, Joanicot M. 36.  2009. Extracting the hydrodynamic resistance of droplets from their behavior in microchannel networks. Biomicrofluidics 3:012804 [Google Scholar]
  37. Dressler OJ, Yang T, Chang SI, Choo J, Wootton RCR, deMello AJ. 37.  2015. Continuous and low error-rate passive synchronization of pre-formed droplets. RSC Adv 5:6048399–405 [Google Scholar]
  38. Link DR, Anna SL, Weitz DA, Stone HA. 38.  2004. Geometrically mediated breakup of drops in microfluidic devices. Phys. Rev. Lett. 92:5054503 [Google Scholar]
  39. Priest C, Herminghaus S, Seemann R. 39.  2006. Controlled electrocoalescence in microfluidics: targeting a single lamella. Appl. Phys. Lett. 89:134101 [Google Scholar]
  40. Bremond N, Thiam AR, Bibette J. 40.  2008. Decompressing emulsion droplets favors coalescence. Phys. Rev. Lett. 100:2024501 [Google Scholar]
  41. Niu X, Gulati S, Edel JB, deMello AJ. 41.  2008. Pillar-induced droplet merging in microfluidic circuits. Lab Chip 8:111837–41 [Google Scholar]
  42. Baroud CN, de Saint Vincent MR, Delville JP. 42.  2007. An optical toolbox for total control of droplet microfluidics. Lab Chip 7:81029–33 [Google Scholar]
  43. Ahn K, Agresti J, Chong H, Marquez M, Weitz DA. 43.  2006. Electrocoalescence of drops synchronized by size-dependent flow in microfluidic channels. Appl. Phys. Lett. 88:264105 [Google Scholar]
  44. Niu XZ, Gielen F, Edel JB, deMello AJ. 44.  2011. A microdroplet dilutor for high-throughput screening. Nat. Chem. 3:6437–42 [Google Scholar]
  45. Abate AR, Hung T, Mary P, Agresti JJ, Weitz DA. 45.  2010. High-throughput injection with microfluidics using picoinjectors. PNAS 107:4519163–66 [Google Scholar]
  46. Niu XZ, Gielen F, deMello AJ, Edel JB. 46.  2009. Electro-coalescence of digitally controlled droplets. Anal. Chem. 81:177321–25 [Google Scholar]
  47. Tan YC, Ho YL, Lee AP. 47.  2008. Microfluidic sorting of droplets by size. Microfluid Nanofluid 4:4343–48 [Google Scholar]
  48. Hatch AC, Patel A, Beer NR, Lee AP. 48.  2013. Passive droplet sorting using viscoelastic flow focusing. Lab Chip 13:71308–15 [Google Scholar]
  49. Baret JC, Miller OJ, Taly V, Ryckelynck M, El-Harrak A. 49.  et al. 2009. Fluorescence-activated droplet sorting (FADS): efficient microfluidic cell sorting based on enzymatic activity. Lab Chip 9:131850–58 [Google Scholar]
  50. Zang E, Brandes S, Tovar M, Martin K, Mech F. 50.  et al. 2013. Real-time image processing for label-free enrichment of Actinobacteria cultivated in picolitre droplets. Lab Chip 13:183707–13 [Google Scholar]
  51. Abate AR, Agresti JJ, Weitz DA. 51.  2010. Microfluidic sorting with high-speed single-layer membrane valves. Appl. Phys. Lett. 96:2035069 [Google Scholar]
  52. Schmid L, Weitz DA, Franke T. 52.  2014. Sorting drops and cells with acoustics: acoustic microfluidic fluorescence-activated cell sorter. Lab Chip 14:193710–18 [Google Scholar]
  53. Sciambi A, Abate AR. 53.  2015. Accurate microfluidic sorting of droplets at 30 kHz. Lab Chip 15:147–51 [Google Scholar]
  54. i Solvas XC, Niu XZ, Leeper K, Cho S, Chang SI. 54.  et al. 2011. Fluorescence detection methods for microfluidic droplet platforms. J. Vis. Exp. 58:3437 [Google Scholar]
  55. Bringer MR, Gerdts CJ, Song H, Tice JD, Ismagilov RF. 55.  2004. Microfluidic systems for chemical kinetics that rely on chaotic mixing in droplets. Philos. Trans. R. Soc. A 362:18181087–104 [Google Scholar]
  56. Huebner A, Srisa-Art M, Holt D, Abell C, Hollfelder F. 56.  et al. 2007. Quantitative detection of protein expression in single cells using droplet microfluidics. Chem. Commun.121218–20 [Google Scholar]
  57. Brouzes E, Medkova M, Savenelli N, Marran D, Twardowski M. 57.  et al. 2009. Droplet microfluidic technology for single-cell high-throughput screening. PNAS 106:3414195–200 [Google Scholar]
  58. Sjostrom SL, Joensson HN, Svahn HA. 58.  2013. Multiplex analysis of enzyme kinetics and inhibition by droplet microfluidics using picoinjectors. Lab Chip 13:91754–61 [Google Scholar]
  59. Zhong Q, Bhattacharya S, Kotsopoulos S, Olson J, Taly V. 59.  et al. 2011. Multiplex digital PCR: breaking the one target per color barrier of quantitative PCR. Lab Chip 11:132167–74 [Google Scholar]
  60. Cole RH, de Lange N, Gartner ZJ, Abate AR. 60.  2015. Compact and modular multicolour fluorescence detector for droplet microfluidics. Lab Chip 15:132754–58 [Google Scholar]
  61. Edelhoch H, Brand L, Wilchek M. 61.  1967. Fluorescence studies with tryptophyl peptides. Biochemistry 6:2547–59 [Google Scholar]
  62. Bugiel I, Konig K, Wabnitz H. 62.  1989. Investigation of cells by fluorescence laser microscopy with subnanosecond time resolution. Lasers Life Sci 3:147–53 [Google Scholar]
  63. Srisa-Art M, Dyson EC, deMello AJ, Edel JB. 63.  2008. Monitoring of real-time streptavidin-biotin binding kinetics using droplet microfluidics. Anal. Chem. 80:187063–67 [Google Scholar]
  64. i Solvas XC, Srisa-Art M, deMello AJ, Edel JB. 64.  2010. Mapping of fluidic mixing in microdroplets with 1 μs time resolution using fluorescence lifetime imaging. Anal. Chem. 82:93950–56 [Google Scholar]
  65. Benz C, Retzbach H, Nagl S, Belder D. 65.  2013. Protein-protein interaction analysis in single microfluidic droplets using FRET and fluorescence lifetime detection. Lab Chip 13:142808–14 [Google Scholar]
  66. Chan KLA, Kazarian SG. 66.  2016. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) imaging of tissues and live cells. Chem. Soc. Rev. 45:71850–64 [Google Scholar]
  67. Lewis EN, Treado PJ, Reeder RC, Story GM, Dowrey AE. 67.  et al. 1995. Fourier transform spectroscopic imaging using an infrared focal-plane array detector. Anal. Chem. 67:193377–81 [Google Scholar]
  68. Schlücker S. 68.  2014. Surface-enhanced Raman spectroscopy: concepts and chemical applications. Angew. Chem. Int. Ed. 53:194756–95 [Google Scholar]
  69. Cristobal G, Arbouet L, Sarrazin F, Talaga D, Bruneel JL. 69.  et al. 2006. On-line laser Raman spectroscopic probing of droplets engineered in microfluidic devices. Lab Chip 6:91140–46 [Google Scholar]
  70. Wang G, Lim C, Chen L, Chon H, Choo J. 70.  et al. 2009. Surface-enhanced Raman scattering in nanoliter droplets: towards high-sensitivity detection of mercury (II) ions. Anal. Bioanal. Chem. 394:71827–32 [Google Scholar]
  71. Cecchini MP, Hong J, Lim C, Choo J, Albrecht T. 71.  et al. 2011. Ultrafast surface enhanced resonance Raman scattering detection in droplet-based microfluidic systems. Anal. Chem. 83:83076–81 [Google Scholar]
  72. Chan KLA, Niu X, deMello AJ, Kazarian SG. 72.  2011. Generation of chemical movies: FT-IR spectroscopic imaging of segmented flows. Anal. Chem. 83:93606–9 [Google Scholar]
  73. Müller T, Ruggeri FS, Kulik AJ, Shimanovich U, Mason TO. 73.  et al. 2014. Nanoscale spatially resolved infrared spectra from single microdroplets. Lab Chip 14:71315–19 [Google Scholar]
  74. Hassan SU, Nightingale AM, Niu X. 74.  2016. Continuous measurement of enzymatic kinetics in droplet flow for point-of-care monitoring. Analyst 141:113266–73 [Google Scholar]
  75. Neil SRT, Rushworth CM, Vallance C, Mackenzie SR. 75.  2011. Broadband cavity-enhanced absorption spectroscopy for real time, in situ spectral analysis of microfluidic droplets. Lab Chip 11:233953–55 [Google Scholar]
  76. Hung LH, Choi KM, Tseng WY, Tan YC, Shea KJ, Lee AP. 76.  2006. Alternating droplet generation and controlled dynamic droplet fusion in microfluidic device for CdS nanoparticle synthesis. Lab Chip 6:2174–78 [Google Scholar]
  77. Rundlett KL, Armstrong DW. 77.  1996. Mechanism of signal suppression by anionic surfactants in capillary electrophoresis-electrospray ionization mass spectrometry. Anal. Chem. 68:193493–97 [Google Scholar]
  78. Fidalgo LM, Whyte G, Ruotolo BT, Benesch JL, Stengel F. 78.  et al. 2009. Coupling microdroplet microreactors with mass spectrometry: reading the contents of single droplets online. Angew. Chem. Int. Ed. 48:203665–68 [Google Scholar]
  79. Kelly RT, Page JS, Marginean I, Tang K, Smith RD. 79.  2009. Dilution-free analysis from picoliter droplets by nano-electrospray ionization mass spectrometry. Angew. Chem. Int. Ed. 48:376832–35 [Google Scholar]
  80. Smith CA, Li X, Mize TH, Sharpe TD, Graziani EI. 80.  et al. 2013. Sensitive, high throughput detection of proteins in individual, surfactant-stabilized picoliter droplets using nanoelectrospray ionization mass spectrometry. Anal. Chem. 85:83812–16 [Google Scholar]
  81. Pereira F, Niu XZ, deMello AJ. 81.  2013. A nano LC-MALDI mass spectrometry droplet interface for the analysis of complex protein samples. PLOS ONE 8:5e63087 [Google Scholar]
  82. Küster SK, Fagerer SR, Verboket PE, Eyer K, Jefimovs K. 82.  et al. 2013. Interfacing droplet microfluidics with matrix-assisted laser desorption/ionization mass spectrometry: label-free content analysis of single droplets. Anal. Chem. 85:31285–89 [Google Scholar]
  83. Olson DL, Lacey ME, Sweedler JV. 83.  1998. High-resolution microcoil NMR for analysis of mass-limited, nanoliter samples. Anal. Chem. 70:3645–50 [Google Scholar]
  84. Kautz RA, Goetzinger WK, Karger BL. 84.  2005. High-throughput microcoil NMR of compound libraries using zero-dispersion segmented flow analysis. J. Comb. Chem. 7:114–20 [Google Scholar]
  85. Zheng B, Tice JD, Roach LS, Ismagilov RF. 85.  2004. A droplet-based, composite PDMS/glass capillary microfluidic system for evaluating protein crystallization conditions by microbatch and vapor-diffusion methods with on-chip X-ray diffraction. Angew. Chem. Int. Ed. 43:192508–11 [Google Scholar]
  86. Stehle R, Goerigk G, Wallacher D, Ballauff M, Seiffert S. 86.  2013. Small-angle X-ray scattering in droplet-based microfluidics. Lab Chip 13:81529–37 [Google Scholar]
  87. Pompano RR, Liu WS, Du WB, Ismagilov RF. 87.  2011. Microfluidics using spatially defined arrays of droplets in one, two, and three dimensions. Annu. Rev. Anal. Chem. 4:59–81 [Google Scholar]
  88. Shi WW, Qin JH, Ye NN, Lin BC. 88.  2008. Droplet-based microfluidic system for individual Caenorhabditis elegans assay. Lab Chip 8:91432–35 [Google Scholar]
  89. Lan F, Haliburton JR, Yuan A, Abate AR. 89.  2016. Droplet barcoding for massively parallel single-molecule deep sequencing. Nat. Commun. 7:11784 [Google Scholar]
  90. Huebner A, Bratton D, Whyte G, Yang M, deMello AJ. 90.  et al. 2009. Static microdroplet arrays: a microfluidic device for droplet trapping, incubation and release for enzymatic and cell-based assays. Lab Chip 9:5692–98 [Google Scholar]
  91. Wang W, Yang C, Li CM. 91.  2009. On-demand microfluidic droplet trapping and fusion for on-chip static droplet assays. Lab Chip 9:111504–6 [Google Scholar]
  92. Gerver RE, Gómez-Sjöberg R, Baxter BC, Thorn KS, Fordyce PM. 92.  et al. 20012. Programmable microfluidic synthesis of spectrally encoded microspheres. Lab Chip 12:224716–23 [Google Scholar]
  93. Lim J, Caen O, Vrignon J, Konrad M, Taly V, Baret JC. 93.  2015. Parallelized ultra-high throughput microfluidic emulsifier for multiplex kinetic assays. Biomicrofluidics 9:034101 [Google Scholar]
  94. Hatch AC, Fisher JS, Tovar AR, Hsieh AT, Lin R. 94.  et al. 2011. 1-million droplet array with wide-field fluorescence imaging for digital PCR. Lab Chip 11:223838–45 [Google Scholar]
  95. Schaerli Y, Wootton RC, Robinson T, Stein V, Dunsby C. 95.  et al. 2009. Continuous-flow polymerase chain reaction of single-copy DNA in microfluidic microdroplets. Anal. Chem. 81:1302–6 [Google Scholar]
  96. Hindson BJ, Ness KD, Masquelier DA, Belgrader P, Heredia NJ. 96.  et al. 2011. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal. Chem. 83:228604–10 [Google Scholar]
  97. Dhanasekaran S, Doherty TM, Kenneth J, Group TBTS. 97.  2010. Comparison of different standards for real-time PCR-based absolute quantification. J. Immunol. Methods 354:1–234–39 [Google Scholar]
  98. Beer NR, Hindson BJ, Wheeler EK, Hall SB, Rose KA. 98.  et al. 2007. On-chip, real-time, single-copy polymerase chain reaction in picoliter droplets. Anal. Chem. 79:228471–75 [Google Scholar]
  99. Eastburn DJ, Huang Y, Pellegrino M, Sciambi A, Ptacek LJ, Abate AR. 99.  2015. Microfluidic droplet enrichment for targeted sequencing. Nucleic Acids Res 43:13e86 [Google Scholar]
  100. Metzker ML. 100.  2010. Sequencing technologies—the next generation. Nat. Rev. Genet. 11:131–46 [Google Scholar]
  101. Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K. 101.  et al. 2015. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161:51202–14 [Google Scholar]
  102. Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A. 102.  et al. 2015. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161:51187–201 [Google Scholar]
  103. Khorshidi MA, Rajeswari PKP, Wählby C, Joensson HN, Svahn HA. 103.  2014. Automated analysis of dynamic behavior of single cells in picoliter droplets. Lab Chip 14:5931–37 [Google Scholar]
  104. Hofmann TW, Anselmann SH, Janiesch JW, Rademacher A, Bohm CHJ. 104.  2012. Applying microdroplets as sensors for label-free detection of chemical reactions. Lab Chip 12:5916–22 [Google Scholar]
  105. Boedicker JQ, Vincent ME, Ismagilov RF. 105.  2009. Microfluidic confinement of single cells of bacteria in small volumes initiates high-density behavior of quorum sensing and growth and reveals its variability. Angew. Chem. Int. Ed. 48:325908–11 [Google Scholar]
  106. Baraban L, Bertholle F, Salverda MLM, Bremond N, Panizza P. 106.  et al. 2011. Millifluidic droplet analyser for microbiology. Lab Chip 11:234057–62 [Google Scholar]
  107. Damodaran SP, Eberhard S, Boitard L, Rodriguez JG, Wang Y. 107.  et al. 2015. A millifluidic study of cell-to-cell heterogeneity in growth-rate and cell-division capability in populations of isogenic cells of Chlamydomonas reinhardtii. PLOS ONE 10:3e0118987 [Google Scholar]
  108. Jakiela S, Kaminski TS, Cybulski O, Weibel DB, Garstecki P. 108.  2013. Bacterial growth and adaptation in microdroplet chemostats. Angew. Chem. Int. Ed. 52:348908–11 [Google Scholar]
  109. Weitz M, Mückl A, Kapsner K, Berg R, Meyer A, Simmel FC. 109.  2014. Communication and computation by bacteria compartmentalized within microemulsion droplets. J. Am. Chem. Soc. 136:172–75 [Google Scholar]
  110. Stein V, Alexandrov K. 110.  2015. Synthetic protein switches: design principles and applications. Trends Biotechnol 33:2101–10 [Google Scholar]
  111. Koshland DE. 111.  2002. The seven pillars of life. Science 295:55632215–16 [Google Scholar]
  112. Hasatani K, Leocmach M, Genot AJ, Éstevez-Torres A, Fujii T, Rondelez Y. 112.  2013. High-throughput and long-term observation of compartmentalized biochemical oscillators. Chem. Commun. 49:738090–92 [Google Scholar]
  113. Weitz M, Kim J, Kapsner K, Winfree E, Franco E, Simmel FC. 113.  2014. Diversity in the dynamical behaviour of a compartmentalized programmable biochemical oscillator. Nat. Chem. 6:5295–302 [Google Scholar]
  114. Genot AJ, Baccouche A, Sieskind R, Aubert-Kato N, Bredeche N. 114.  et al. 2016. High-resolution mapping of bifurcations in nonlinear biochemical circuits. Nat. Chem. 8:8760–67 [Google Scholar]
  115. Elowitz MB, Levine AJ, Siggia ED, Swain PS. 115.  2002. Stochastic gene expression in a single cell. Science 297:55841183–86 [Google Scholar]
  116. Hansen MM, Meijer LH, Spruijt E, Maas RJ, Rosquelles MV. 116.  et al. 2016. Macromolecular crowding creates heterogeneous environments of gene expression in picolitre droplets. Nat. Nanotechnol. 11:2191–97 [Google Scholar]
  117. Sokolova E, Spruijt E, Hansen MM, Dubuc E, Groen J. 117.  et al. 2013. Enhanced transcription rates in membrane-free protocells formed by coacervation of cell lysate. PNAS 110:2911692–97 [Google Scholar]
  118. Schwarz-Schilling M, Aufinger L, Mückl A, Simmel FC. 118.  2016. Chemical communication between bacteria and cell-free gene expression systems within linear chains of emulsion droplets. Integr. Biol. 8:4564–70 [Google Scholar]
  119. Miyazaki M, Chiba M, Eguchi H, Ohki T, Ishiwata S. 119.  2015. Cell-sized spherical confinement induces the spontaneous formation of contractile actomyosin rings in vitro. Nat. Cell Biol. 17:4480–89 [Google Scholar]
  120. Tawfik DS, Griffiths AD. 120.  1998. Man-made cell-like compartments for molecular evolution. Nat. Biotechnol. 16:7652–56 [Google Scholar]
  121. Miller OJ, Bernath K, Agresti JJ, Amitai G, Kelly BT. 121.  et al. 2006. Directed evolution by in vitro compartmentalization. Nat. Methods 3:7561–70 [Google Scholar]
  122. Agresti JJ, Antipov E, Abate AR, Ahn K, Rowat AC. 122.  et al. 2010. Ultrahigh-throughput screening in drop-based microfluidics for directed evolution. PNAS 107:94004–9 [Google Scholar]
  123. Fischlechner M, Schaerli Y, Mohamed MF, Patil S, Abell C, Hollfelder F. 123.  2014. Evolution of enzyme catalysts caged in biomimetic gel-shell beads. Nat. Chem. 6:9791–96 [Google Scholar]
  124. Zinchenko A, Devenish SRA, Kintses B, Colin PY, Fischlechner M, Hollfelder F. 124.  2014. One in a million: flow cytometric sorting of single cell-lysate assays in monodisperse picolitre double emulsion droplets for directed evolution. Anal. Chem. 86:52526–33 [Google Scholar]
  125. Obexer R, Pott M, Zeymer C, Griffiths AD, Hilvert D. 125.  2016. Efficient laboratory evolution of computationally designed enzymes with low starting activities using fluorescence-activated droplet sorting. Protein Eng. Des. Sel. 29:9355–66 [Google Scholar]
  126. Kintses B, Hein C, Mohamed MF, Fischlechner M, Courtois F. 126.  et al. 2012. Picoliter cell lysate assays in microfluidic droplet compartments for directed enzyme evolution. Chem. Biol. 19:81001–9 [Google Scholar]
  127. Pelleter J, Renaud F. 127.  2009. Facile, fast and safe process development of nitration and bromination reactions using continuous flow reactors. Org. Process. Res. Dev. 13:4698–705 [Google Scholar]
  128. Song H, Ismagilov RF. 128.  2003. Millisecond kinetics on a microfluidic chip using nanoliters of reagents. J. Am. Chem. Soc. 125:4714613–19 [Google Scholar]
  129. Mazutis L, Baret JC, Treacy P, Skhiri Y, Araghi AF. 129.  et al. 2009. Multi-step microfluidic droplet processing: kinetic analysis of an in vitro translated enzyme. Lab Chip 9:202902–8 [Google Scholar]
  130. Maillot S, Carvalho A, Vola JP, Boudier C, Mély Y. 130.  et al. 2014. Out-of-equilibrium biomolecular interactions monitored by picosecond fluorescence in microfluidic droplets. Lab Chip 14:101767–74 [Google Scholar]
  131. Fradet E, Bayer C, Hollfelder F, Baroud CN. 131.  2015. Measuring fast and slow enzyme kinetics in stationary droplets. Anal. Chem. 87:2311915–22 [Google Scholar]
  132. Miller OJ, El Harrak A, Mangeat T, Baret JC, Frenz L. 132.  et al. 2012. High-resolution dose-response screening using droplet-based microfluidics. PNAS 109:2378–83 [Google Scholar]
  133. Taylor G. 133.  1953. Dispersion of soluble matter in solvent flowing slowly through a tube. Proc. R. Soc. A 219:1137186–203 [Google Scholar]
  134. Han ZY, Chang YY, Au SWN, Zheng B. 134.  2012. Measuring rapid kinetics by a potentiometric method in droplet-based microfluidic devices. Chem. Commun. 48:101601–3 [Google Scholar]
  135. Lignos I, Stavrakis S, Kilaj A, deMello AJ. 135.  2015. Millisecond-timescale monitoring of PbS nanoparticle nucleation and growth using droplet-based microfluidics. Small 11:324009–17 [Google Scholar]
  136. Lignos I, Stavrakis S, Nedelcu G, Protesescu L, DeMello AJ, Kovalenko MV. 136.  2016. Synthesis of cesium lead halide perovskite nanocrystals in a droplet-based microfluidic platform: fast parametric space mapping. Nano Lett 16:31869–77 [Google Scholar]
  137. Maceiczyk RM, Lignos IG, deMello AJ. 137.  2015. Online detection and automation methods in microfluidic nanomaterial synthesis. Curr. Opin. Chem. Eng. 8:29–35 [Google Scholar]
  138. Abolhasani M, Coley CW, Xie LS, Chen O, Bawendi MG, Jensen KF. 138.  2015. Oscillatory microprocessor for growth and in situ characterization of semiconductor nanocrystals. Chem. Mater. 27:176131–38 [Google Scholar]
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