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Lab-on-a-chip in Vitro Compartmentalization Technologies for Protein Studies

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Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 110))

Abstract

In vitro compartmentalization (IVC) is a powerful tool for studying protein–proteinreactions, due to its high capacity and the versatility of droplet technologies. IVC bridges thegap between chemistry and biology as it enables the incorporation of unnatural amino acids with modificationsinto biological systems, through protein transcription and translation reactions, in a cell-likemicrodrop environment. The quest for the ultimate chip for protein studies using IVC is the drivefor the development of various microfluidic droplet technologies to enable these unusual biochemicalreactions to occur. These techniques have been shown to generate precise microdrops with a controlledsize. Various chemical and physical phenomena have been utilized for on-chip manipulation to allowthe droplets to be generated, fused, and split. Coupled with detection techniques, droplets can besorted and selected. These capabilities allow directed protein evolution to be carried out on a microchip.With further technological development of the detection module, factors such as addressable storage,transport and interfacing technologies, could be integrated and thus provide platforms for proteinstudies with high efficiency and accuracy that conventional laboratories cannot achieve.

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References

  1. Xie J, Schultz PG (2005) Adding amino acids to the genetic repertoire. Curr Opin Chem Biol 9:548–554

    Article  CAS  Google Scholar 

  2. Tawfik DS, Griffiths AD (1998) Man-made cell-like compartments for molecular evolution. Nat Biotechnol 16:652–656

    Article  CAS  Google Scholar 

  3. Aharoni A, Griffiths AD, Tawfik DS (2005) High-throughput screens and selections of enzyme-encoding genes. Nat Biotechnol 9:210–216

    CAS  Google Scholar 

  4. Amstutz P et al. (2001) In vitro display technologies: novel developments and applications. Curr Opin Biotechnol 12:400–405

    Article  CAS  Google Scholar 

  5. Dower WJ, Mattheakis LC (2002) In vitro selection as a powerful tool for the applied evolution of proteins and peptides. Curr Opin Chem Biol 6:390–398

    Article  CAS  Google Scholar 

  6. Griffiths AD, Tawfik DS (2000) Man-made enzymes – from design to in vitro compartmentalisation. Curr Opin Biotechnol 11:338–353

    Article  CAS  Google Scholar 

  7. Griffiths AD, Tawfik DS (2006) Miniaturising the laboratory in emulsion droplets. Trends Biotechnol 24(9):395–402

    Article  CAS  Google Scholar 

  8. Jestin J-L, Kaminski PA (2004) Directed enzyme evolution and selections for catalysis based on product formation. J Biotechnol 113:85–103

    Article  CAS  Google Scholar 

  9. Kelly BT et al. (2007) Miniaturizing chemistry and biology in microdroplets. Chem Commun, pp 1773–1788

    Google Scholar 

  10. Leamon LH et al. (2006) Overview: methods and applications for droplet compartmentalization of biology. Nat Methods 3(7):541–543

    Article  CAS  Google Scholar 

  11. Rothe A, Surjadi RN, Power BE (2006) Novel proteins in emulsions using in vitro compartmentalization. Trends Biotechnol 24:587–592

    Article  CAS  Google Scholar 

  12. Song H, Chen DL, Ismagilov RF (2006) Reactions in droplets in microfluidic channels. Angew Chem Int Edit 45:7336–7356

    Article  CAS  Google Scholar 

  13. DeMello A (2006) Control and detection of chemical reactions in microfluidic systems. Nature 442:394–402

    Article  CAS  Google Scholar 

  14. Cristini V, Tan Y-C (2004) Theory and numerical simulation of droplet dynamics in complex flows – a review. Lab Chip 4:257–264

    Article  CAS  Google Scholar 

  15. Atencia J, Beebe DJ (2005) Controlled microfluidic interfaces. Nature 437:648–655

    Article  CAS  Google Scholar 

  16. Squires TM, Quake SR (2005) Microfluidics: fluid physics at the nanoliter scale. Rev Mod Phys 77:977–1026

    Article  CAS  Google Scholar 

  17. Doktycz MJ, Simpson ML (2007) Nano-enabled synthetic biology. Mol Syst Biol 3:1–10

    Article  Google Scholar 

  18. Arnold FH (1998) Design by directed evolution. Acc Chem Res 31:125–131

    Article  CAS  Google Scholar 

  19. Arnold FH, Georgiou G (2003) Directed enzyme evolution. Methods Molec Biol 230

    Google Scholar 

  20. Besenmatter W, Kast P, Hilvert D (2004) New enzymes from combinatorial library modules. In: Robertson D, Noel JP (eds) Methods in enzymology, vol 388. Academic, New York, pp 91–102

    Google Scholar 

  21. Otten LG, Quax WJ (2005) Directed evolution-selecting today's biocatalysts. Biomolec Eng 22:1–9

    Google Scholar 

  22. Voigt CA, Kauffman S, Wang Z-G (2001) Rational evolutionary design: the theory of in vitro protein evolution. Adv Protein Chem 55:79–160

    Article  Google Scholar 

  23. Ghadessy FJ, Holliger P (2004) A novel emulsion mixture for in vitro compartmentalization of transcription and translation in the rabbit reticulocyte system. Protein Eng Des Sel 17(3):201–204

    Article  CAS  Google Scholar 

  24. Yang H et al. (2003) Evolution of an organophosphate-degrading enzyme: a comparison of natural and directed evolution. Protein Eng 16(2):135–145

    Article  CAS  Google Scholar 

  25. Bernath K et al. (2004) In vitro compartmentalization by double emulsions: sorting and gene enrichment by fluorescence activated cell sorting. Anal Biochem 325:151–157

    Article  CAS  Google Scholar 

  26. Johannes TW, Zhao H (2006) Directed evolution of enzymes and biosynthetic pathways. Curr Opin Microbiol 9:261–267

    Article  CAS  Google Scholar 

  27. Miller OJ et al. (2006) Directed evolution by in vitro compartmentalization. Nat Methods 3(7):561–570

    Article  CAS  Google Scholar 

  28. Williams R et al. (2006) Amplification of complex gene libraries by emulsion PCR. Nat Methods 3(7):545–550

    Article  CAS  Google Scholar 

  29. Doi N, Yanagawa H (1999) STABLE: Protein–DNA fusion system for screening of combinatorial protein libraries in vitro. FEBS Lett 457:227–230

    Article  CAS  Google Scholar 

  30. Sepp A, Choo Y (2005) Cell-free selection of zinc finger DNA binding proteins using in vitro compartmentalization. J Mol Biol 354:212–219

    Article  CAS  Google Scholar 

  31. Yonezawa M et al. (2003) DNA display for in vitro selection of diverse peptide libraries. Nucleic Acids Res 31:e118

    Article  CAS  Google Scholar 

  32. Doi N et al. (2004) In vitro selection of restriction endonucleases by in vitro compartmentalization. Nucleic Acids Res 32(12):e95

    Article  CAS  Google Scholar 

  33. Pietrini AV, Luisi PL (2004) Cell-free protein synthesis through solubilisate exchange in water/oil emulsion compartments. ChemBioChem 5:1055–1062

    Article  CAS  Google Scholar 

  34. Agresti JJ et al. (2005) Selection of ribozymes that catalyse multiple-turnover Diels–Alder cycloadditions by using in vitro compartmentalization. PNAS 102(45):16170–16175

    Article  CAS  Google Scholar 

  35. Cohen HM, Tawfik DS, Griffiths AD (2004) Altering the sequence specificity of HaeIII methyltransferase by directed evolution using in vitro compartmentalization. Protein Eng Des Sel 17(1):3–11

    Article  CAS  Google Scholar 

  36. Griffiths AD, Tawfik DS (2003) Directed evolution of an extremely fast phosphotriesterase by in vitro compartmentalization. EMBO J 22(1):24–35

    Article  CAS  Google Scholar 

  37. Ghadessy FJ, Ong JL, Holliger P (2001) Directed evolution of polymerase function by compartmentalized self-replication. PNAS 98(8):4552–4557

    Article  CAS  Google Scholar 

  38. Bernath K, Magdassi S, Tawfik DS (2005) Directed evolution of protein inhibitors of DNAnucleases by in vitro compartmentalization (IVC) and nano-droplet delivery. J Mol Biol 345:1015–1026

    Article  CAS  Google Scholar 

  39. Leemhuis H et al. (2005) New genotype–phenotype linkages for directed evolution of functional proteins. Curr Opin Struct Biol 15:472–478

    Article  CAS  Google Scholar 

  40. Endo Y, Sawasaki T (2006) Cell-free expression systems for eukaryotic protein production. Curr Opin Biotechnol 17:373–380

    Article  CAS  Google Scholar 

  41. Endo Y, Sawasaki T (2004) High-throughput, genome-scale protein production method based on the wheat germ cell-free expression system. J Strucz Funct Genomics 5:45–57

    Google Scholar 

  42. Shimizu Y, Kanamori T, Ueda T (2005) Protein synthesis by pure translation systems. Methods 36:299–304

    Article  CAS  Google Scholar 

  43. Lee ER (2003) Microdrop generation. CRC, Boca Raton

    Google Scholar 

  44. Garstecki P et al. (2006) Formation of droplets and bubbles in a microfluidic T-junction – scaling and mechanism of break-up. Lab Chip 6:437–446

    Article  CAS  Google Scholar 

  45. Husny J et al. (2006) The creation of drops in T-shaped microfluidic devices with the modified laser LIGA technique: I. Fabrication. Smart Matter Struct 15:S117–S123

    Article  CAS  Google Scholar 

  46. Menetrier L, Tabeling P (2006) Droplet break-up in junctions: the concept of a critical length. In: Proceedings MicroTAS2006, Tokyo, 5–9 Nov 2006. Society for Chemistry and Micro-Nano Systems (CHEMINAS), Japan, 2006, pp 98–101

    Google Scholar 

  47. Nisisako T, Okushima S, Torii T (2005) Controlled formulation of monodisperse double emulsions in a multiple-phase microfluidic system. Soft Matter 1:23–27

    Article  CAS  Google Scholar 

  48. Nisisako T, Torii T, Higuchi T (2002) Droplet formation in a microchannel network. Lab Chip 2:24–26

    Article  CAS  Google Scholar 

  49. Song H et al. (2003) Experimental test of scaling of mixing by chaotic advection in droplets moving through microfluidic channels. Appl Phys Lett 83(22):4664–4666

    Article  CAS  Google Scholar 

  50. Tice JD et al. (2003) Formation of droplets and mixing in multiphase microfluidics at low values of the Reynolds and the capillary numbers. Langmuir 19:9127–9133

    Article  CAS  Google Scholar 

  51. Van der Graaf S et al. (2005) Droplet formation in a T-shaped microchannel junction: a model system for membrane emulsification. Colloid Surf A 266:106–116

    Article  CAS  Google Scholar 

  52. Kohler JM, Kirner T (2005) Nanoliter segment formation in micro fluid devices for chemical and biological micro serial flow processes in dependence on flow rate and viscosity. Sens Actuators A 119:19–27

    Article  CAS  Google Scholar 

  53. Fuerstman MJ, Garstecki P, Whitesides GM (2007) Coding/decoding and reversibility of droplet trains in microfluidic networks. Science 315:828–832

    Article  CAS  Google Scholar 

  54. He M et al. (2005) Selective encapsulation of single cells and subcellular organelles into picoliter- and femtoliter-volume droplets. Anal Chem 77:1539–1544

    Article  CAS  Google Scholar 

  55. Thorsen T et al. (2001) Dynamic pattern formation in a vesicle-generating microfluidic device. Phys Rev Lett 86:4163–4166

    Article  CAS  Google Scholar 

  56. Chen DL et al. (2007) Using three-phase flow of immiscible liquids to prevent coalescence of droplets in microfluidic channels: criteria to identify the third liquid and validation with protein crystallization. Langmuir 23:2255–2260

    Article  CAS  Google Scholar 

  57. Zheng B et al. (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 Edit 43:2508–2511

    Article  CAS  Google Scholar 

  58. Amici E et al. (2008) Alginate gelation in microfluidic channels. Food Hydrocolloids 2008:97–104

    Article  CAS  Google Scholar 

  59. Huebner A et al. (2007) Quantitative detection of protein expression in single cells using droplet microfluidics. Chem Commun, pp 1218–1220

    Google Scholar 

  60. Sgro AE, Allen PB, Chiu DT (2007) Thermoelectric manipulation of aqueous droplets in microfluidic devices. Anal Chem 79:4845–4851

    Article  CAS  Google Scholar 

  61. Ambravaneswaran B, Wilkes ED, Basarana OA (2002) Drop formation from a capillary tube: comparison of one-dimensional and two-dimensional analyses and occurrence of satellite drops. Phys Fluids 14:(8):2606–2621

    Google Scholar 

  62. Bogy DB (1979) Drop formation in a circular liquid jet. Ann Rev Fluid Mech 11:207–228

    Article  Google Scholar 

  63. Cramer C, Fischer P, Windhab EJ (2004) Drop formation in a Co-flowing ambient fluid. Chem Eng Sci 59:3045–3058

    Article  CAS  Google Scholar 

  64. Lister JR, Stone HA (1998) Capillary breakup of a viscous thread surrounded by another viscous fluid. Phys Fluids 10(11):2758–2764

    Article  CAS  Google Scholar 

  65. Sugiura S et al. (2001) Interfacial tension driven monodispersed droplet formation from microfabricated channel array. Langmuir 17:5562–5566

    Article  CAS  Google Scholar 

  66. Sugiura S et al. (2000) Preparation of monodispersed solid lipid microspheres using a microchannel emulsification technique. J Colloid Interf Sci 227:95–103

    Article  CAS  Google Scholar 

  67. Taylor GI (1934) The formation of emulsions in definable fields of flow. Proc R Soc London A 146:501–523

    Article  CAS  Google Scholar 

  68. Tomotika S (1935) On the instability of a cylindrical thread of a viscous liquid surrounded by another viscous fluid. Proc R Soc London A CL:322–337

    Google Scholar 

  69. Umbanhowar PB, Prasad V, Weitz DA (2000) Monodisperse emulsion generation via drop break off in a coflowing stream. Langmuir 16:347–351

    Article  CAS  Google Scholar 

  70. Zhang DF, Stone HA (1997) Drop formation in viscous flows at a vertical capillary tube. Phys Fluids 9(8):2234–2242

    Article  CAS  Google Scholar 

  71. Zhang X, Basaran OA (1995) An experimental study of dynamics of drop formation. Phys Fluids 7(6):1184–1203

    Article  CAS  Google Scholar 

  72. Anna SL, Bontoux N, Stone HA (2003) Formation of dispersions using flow focusing in microchannels. Appl Phys Lett 82:364–366

    Article  CAS  Google Scholar 

  73. Baroud CN, Robert de Saint Vincent M, Delville J-P (2007) An optical toolbox for total control of droplet microfluidics. Lab Chip 7:1029–1033

    Article  CAS  Google Scholar 

  74. Dittrich PS, Jahnz M, Schwille P (2005) A new embedded process for compartmentalized cell-free protein expression and on-line detection in microfluidic devices. Communications 6:811–814

    CAS  Google Scholar 

  75. Joanicot M, Ajdari A (2005) Droplet control for microfluidics. Science 309:887–888

    Article  CAS  Google Scholar 

  76. Luo C et al. (2006) Picoliter-volume aqueous droplets in oil: electrochemical detection and yeast cell electroporation. Electrophoresis 27:1977–1983

    Article  CAS  Google Scholar 

  77. Shestopalov I, Tice JD, Ismagilov RF (2004) Multi-step synthesis of nanoparticles performed on millisecond time scale in a microfluidic droplet-based system. Lab Chip 4:316–321

    Article  CAS  Google Scholar 

  78. Tan Y-C, Cristini V, Lee AP (2006) Monodispersed microfluidic droplet generation by shear focusing microfluidic device. Sens Actuators B 114:350–356

    Article  CAS  Google Scholar 

  79. Tan Y-C et al. (2004) Design of microfluidic channel geometries for the control of droplet volume, chemical concentration, and sorting. Lab Chip 4:292–298

    Article  CAS  Google Scholar 

  80. Tolosa L-I et al. (2006) Combined effects of formulation and stirring on emulsion drop size in the vicinity of three-phase behavior of surfactant-oil water systems. Indian Eng Chem Res 45:3810–3814

    Article  CAS  Google Scholar 

  81. Utada AS et al. (2005) Monodisperse double emulsions generated from a microcapillary device. Science 308:537–541

    Article  CAS  Google Scholar 

  82. Chan EM, Alivisatos AP, Mathies RA (2005) High-temperature microfluidic synthesis of CdSe nanocrystals in nanoliter droplets. J Am Chem Soc 127:13854–13861

    Article  CAS  Google Scholar 

  83. Dreyfus R, Tabeling P, Willaime H (2003) Ordered and disordered patterns in two-phase flows in microchannels. Phys Rev Lett 90(14):144505

    Article  CAS  Google Scholar 

  84. He M, Kuo JS, Chiu DT (2005) Electro-generation of single femtoliter- and picoliter-volume aqueous droplets in microfluidic systems. Appl Phys Lett 87:031916

    Article  CAS  Google Scholar 

  85. Nisisako T, Torii T (2007) Formation of biphasic Janus droplets in a microfabricated channel for the synthesis of shape-controlled polymer microparticles. Adv Mater 19(11):1489–1493

    Article  CAS  Google Scholar 

  86. Seo M et al. (2007) Microfluidic consecutive flow-focusing droplet generators. Soft Matter 3:986–992

    Article  CAS  Google Scholar 

  87. Yang C-H et al. (2007) Using a cross-flow microfluidic chip and external crosslinking reaction for monodisperse TPP-chitosan microparticles. Sens Actuators B 124:510–516

    Article  CAS  Google Scholar 

  88. Brouzes E et al. (2006) Droplet-based high-throughput live/dead cell assay. In: Proceedings MicroTAS2006, Tokyo, 5–9 Nov 2006. Society for Chemistry and Micro-Nano Systems (CHEMINAS), Japan, 2006, pp 1043–1045

    Google Scholar 

  89. Baroud CN, Willaime H (2004) Multiphase flows in microfluidics. CR Physique 5:547–555

    Article  CAS  Google Scholar 

  90. Hung L-H et al. (2006) Alternating droplet generation and controlled dynamic droplet fusion in microfluidic device for CdS nanoparticle synthesis. Lab Chip 6:174–178

    Article  CAS  Google Scholar 

  91. Xu Q, Nakajima M (2004) The generation of highly monodisperse droplets through the breakup of hydrodynamically focused microthread in a microfluidic device. Appl Phys Lett 85(17):3726–3728

    Article  CAS  Google Scholar 

  92. Ong W-L et al. (2007) Experimental and computational analysis of droplet formation in a high-performance flow-focusing geometry. Sens Actuators A 138:203–212

    Article  CAS  Google Scholar 

  93. Garstecki P, Stone HA, Whitesides GM (2005) Mechanism for flow-rate controlled breakup in confined geometries: a route to monodisperse emulsions. Phys Rev Lett 94:164501

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  95. Ward T et al. (2005) Microfluidic flow focusing: drop size and scaling in pressure versus flow-rate-driven pumping. Electrophoresis 26(19):3716–3724

    Article  CAS  Google Scholar 

  96. Harvie DJE et al. (2006) Aparametric study of droplet deformation through a microfluidic contraction: low viscosity Newtonian droplets. Chem Eng Sci 61:5149–5158

    Article  CAS  Google Scholar 

  97. Nguyen N-T, Lassemono S, Chollet FA (2006) Optical detection for droplet size control in microfluidic droplet-based analysis systems. Sens Actuators B 117:431–436

    Article  CAS  Google Scholar 

  98. Rayleigh L (1879) On the capillary phenomena of jets. Proc R Soc London A 29:71–79

    Article  Google Scholar 

  99. Zhu Y et al. (2007) Droplets transport in a microfluidic chip for in vitro compartmentalisation. 16th Australasian fluid mechanics conference, Queensland, 3–7 Dec 2007. University of Queensland, Brisbane

    Google Scholar 

  100. Adzima BJ, Velankar SS (2006) Pressure drops for droplet flows in microfluidic channels. J Micromech Microeng 16:1504–1510

    Article  Google Scholar 

  101. Song H, Tice JD, Ismagilov RF (2003) A microfluidic system for controlling reaction networks in time. Angew Chem Int Edit 42:767–772

    Google Scholar 

  102. Tice JD, Lyon AD, Ismagilov RF (2004) Effects of viscosity on droplet formation and mixing in microfluidic channels. Anal Chim Acta 507:73–77

    Article  CAS  Google Scholar 

  103. Eow JS et al. (2001) Electrostatic enhancement of coalescence of water droplets in oil: a review of the current understanding. Chem Eng Sci 84:173–192

    Article  CAS  Google Scholar 

  104. Ahn K et al. (2006) Electrocoalescence of drops synchronized by size-dependent flow in microfluidic channels. Appl Phys Lett 88:264105

    Article  CAS  Google Scholar 

  105. Chabert M, Dorfman KD, Viovy J-L (2005) Droplet fusion by alternating current (AC) field electrocoalescence in microchannels. Electrophoresis 26:3706–3715

    Article  CAS  Google Scholar 

  106. Link DR et al. (2006) Electric control of droplets in microfluidic devices. Angew Chem Int Edit 45:2556–2560

    Article  CAS  Google Scholar 

  107. Priest C, Herminghaus S, Seemannc R (2006) Controlled electrocoalescence in microfluidics: targeting a single lamella. Appl Phys Lett 89:134101

    Article  CAS  Google Scholar 

  108. Schwartz JA, Vykoukal JV, Gascoyne PRC (2004) Droplet-based chemistry on a programmable micro-chip. Lab Chip 4:11–17

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  110. Armani M et al. (2005) Control of microfluidic systems: two examples, results, and challenges. Int J Robust Nonlinear Control 15:785–803

    Article  Google Scholar 

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

    Article  Google Scholar 

  112. Jones TB et al. (2001) Dielectrophoretic liquid actuation and nanodroplet formation. J Appl Phys 89(2):1441–1448

    Article  CAS  Google Scholar 

  113. Lee J, Kim C-JC (2000) Surface-tension-driven microactuation based on continuous electrowetting. J Microelectromech Syst 9(2):171–180

    Article  CAS  Google Scholar 

  114. Paik P, Pamula VK, Fair RB (2003) Rapid droplet mixers for digital microfluidic systems. Lab Chip 3:253–259

    Article  CAS  Google Scholar 

  115. Pollack MG, Shenderovb AD, Fair RB (2002) Electrowetting-based actuation of droplets for integrated microfluidics. Lab Chip 2:96–101

    Article  CAS  Google Scholar 

  116. Washizu M (1998) Electrostatic actuation of liquid droplets for microreactor applications. IEEE Trans Ind Appl 34:732–737

    Article  CAS  Google Scholar 

  117. Fidalgo LM, Abell C, Huck WTS (2007) Surface-induced droplet fusion in microfluidic devices. Lab Chip 7:984–986

    Article  CAS  Google Scholar 

  118. Yan L, Thompson KE, Valsaraj KT (2006) A numerical study on the coalescence of emulsion droplets in a constricted capillary tube. J Colloid Interf Sci 298:832–844

    Article  CAS  Google Scholar 

  119. Kohler JM et al. (2004) Digital reaction technology by micro segmented flow – components, concepts and applications. Chem Eng J 101:201–216

    Article  CAS  Google Scholar 

  120. Liu K et al. (2007) Droplet-based synthetic method using microflow focusing and droplet fusion. Microfluid Nanofluid 3:239–243

    Article  CAS  Google Scholar 

  121. Tan Y-C, Ho YL, Lee AP (2007) Droplet coalescence by geometrically mediated flow in microfluidic channels. Microfluid Nanofluid 3:495–499

    Article  Google Scholar 

  122. Kotz KT, Noble KA, Faris GW (2004) Optical microfluidics. Appl Phys Lett 85(13):2858–2660

    Article  CAS  Google Scholar 

  123. Darhuber AA, Troian SM (2005) Principles of microfluidic actuation by modulation of surface stresses. Ann Rev Fluid Mech 37:425–455

    Article  Google Scholar 

  124. Shikida M et al. (2006) Using wettability and interfacial tension to handle droplets of magnetic beads in a micro-chemical-analysis system. Sens Actuators B 113:563–569

    Article  CAS  Google Scholar 

  125. Heieh AT-H et al. (2006) Monodisperse liposomal gene carrier formulation in picoliter micro-reactor for consistent and efficient gene delivery. In: Proceedings MicroTAS2006, Tokyo, 5–9 Nov 2006. Society for Chemistry and Micro-Nano Systems (CHEMINAS), Japan, 2006, pp 1369–1371

    Google Scholar 

  126. Link DR et al. (2004) Geometrically mediated breakup of drops in microfluidic devices. Phys Rev Lett 92:054503

    Article  CAS  Google Scholar 

  127. Menetrier-Deremble L, Tabeling P (2006) Droplet breakup in microfluidic junctions of arbitary angles. Phys Rev E 74:035303

    Article  CAS  Google Scholar 

  128. Ting TH et al. (2006) Thermally mediated breakup of drops in microchannels. Appl Phys Lett 89:234101

    Article  CAS  Google Scholar 

  129. Arakawa T et al. (2006) Accurate high speed particles and biomolecules sorting microsystem using 3-dimensional sheath flow. In: Proceedings MicroTAS2006, Tokyo, 5–9 Nov 2006. Transducer Research Foundation, Hilton Head, pp 512–514

    Google Scholar 

  130. Chang W-Y, Liu C-H (2006) A cell switching microsystem for single cell sorting application via enhanced dielectrophoresis design. In: Proceedings MicroTAS2006, Tokyo, 5–9 Nov 2006. Transducer Research Foundation, Hilton Head, pp 1474–1476

    Google Scholar 

  131. Dittrich PS, Schwille P (2003) An integrated microfluidic system for reaction, high-sensitivity detection, and sorting of fluorescent cells and particles. Anal Chem 75:5767–5774

    Article  CAS  Google Scholar 

  132. Fu AY et al. (2002) An integrated microfabricated cell sorter. Anal Chem 74:2451–2457

    Article  CAS  Google Scholar 

  133. Fu AY et al. (1999) A microfabricated fluorescence-activated cell sorter. Nat Biotechnol 17:1109–1111

    Article  CAS  Google Scholar 

  134. Gawad S, Schild L, Renaud P (2001) Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing. Lab Chip 1:76–82

    Article  CAS  Google Scholar 

  135. Grier DG (2003) A revolution in optical manipulation. Nature 424:810–816

    Article  CAS  Google Scholar 

  136. MacDonald MP, Dholakia GCSK (2003) Microfluidic sorting in an optical lattice. Nature 426:421–424

    Article  CAS  Google Scholar 

  137. McClain MA et al. (2003) Microfluidic devices for chemical analysis of cells. Anal Chem 75:5646–5655

    Article  CAS  Google Scholar 

  138. Perroud TD, Patel KD (2006) Rapid fluorescence-activated cell sorting with optical-force deflection in a microfluidic device. In: Proceedings MicroTAS2006, Tokyo, 5–9 Nov 2006. Transducer Research Foundation, Hilton Head, pp 984–986

    Google Scholar 

  139. Smith AE et al. (2006) Continuous flow particle sorting at low applied electric fields using electrodeless dielectrophoresis in ridged polymeric microstructures. In: Proceedings MicroTAS2006, Tokyo, 5–9 Nov 2006. Transducer Research Foundation, Hilton Head, pp 1187–1189

    Google Scholar 

  140. Wang L et al. (2007) Dielectrophoresis switching with vertical sidewall electrodes for microfluidic flow cytometry. Lab Chip 7:1114–1120

    Article  CAS  Google Scholar 

  141. Wang MM et al. (2005) Microfluidic sorting of mammalian cells by optical force switching. Nat Biotechnol 23:83–87

    Article  CAS  Google Scholar 

  142. Wolff A et al. (2003) Integrating advanced functionality in a microfabricated high-throughput fluorescent-activated cell sorter. Lab Chip 3:22–27

    Article  CAS  Google Scholar 

  143. Yi C et al. (2006) Microfluidics technology for manipulation and analysis of biological cells. Anal Chim Acta 560:1–23

    Article  CAS  Google Scholar 

  144. Bang H et al. (2006) Microfabricated fluorescence-activated cell sorter through hydrodynamic flow manipulation. Microsyst Technol 12:746–753

    Article  CAS  Google Scholar 

  145. Ahn K et al. (2006) Dielectrophoretic manipulation of drops for high-speed microfluidic sorting devices. Appl Phys Lett 88:024104

    Article  CAS  Google Scholar 

  146. Gallardo BS et al. (1999) Electrochemical principles for active control of liquids on submillimeter scales. Science 283:57–60

    Article  CAS  Google Scholar 

  147. Barbulovic-Nad I et al. (2006) DC-dielectrophoretic separation of microparticles using an oil droplet obstacle. Lab Chip 6:274–279

    Article  CAS  Google Scholar 

  148. Baroud CN et al. (2007) Thermocapillary valve for droplet production and sorting. Phys Rev E 75:046302

    Article  CAS  Google Scholar 

  149. Farahi RH et al. (2004) Microfluidic manipulation via marangoni forces. Appl Phys Lett 85(18):4237–4239

    Article  CAS  Google Scholar 

  150. Glockner PS, Naterer GF (2005) Thermocapillary control of microfluidic transport with a stationary cyclic heat source. J Micromech Microeng 15:2216–2229

    Article  Google Scholar 

  151. Chen CC et al. (2004) Design and operation of a microfluidic sorter for Drosophila embryos. Sens Actuators B 102:59–66

    Article  CAS  Google Scholar 

  152. Tan Y-C, Lee AP (2005) Microfluidic separation of satellite droplets as the basis of a monodispersed micron and submicron emulsification system. Lab Chip 5:1178–1183

    Article  CAS  Google Scholar 

  153. Cristobal G et al. (2006) On-line laser Raman spectroscopic probing of droplets engineered in microfluidic devices. Lab Chip 6:1140–1146

    Article  CAS  Google Scholar 

  154. Kim H-S et al. (2006) Magneto-microfluidic device for apototic cell separation. In: Proceedings MicroTAS2006, Tokyo, 5–9 Nov 2006. Transducer Research Foundation, Hilton Head, pp 416–418

    Google Scholar 

  155. Lemoff AV, Lee AP (2003) An AC magnetohydrodynamic microfluidic switch for micro total analysis system. Biomed Microdev 5(1):55–60

    Article  CAS  Google Scholar 

  156. Burnham DR, McGloin D (2006) Holographic optical trapping of aerosol droplets. Opt Express 14(9):4175–4181

    Article  CAS  Google Scholar 

  157. Kovac J, Voldman J (2006) Facile image-based cell sorting using opto-flucs (opto-fluidic cell sorting). In: Proceedings MicroTAS2006, Tokyo, 5–9 Nov 2006. Transducer Research Foundation, Hilton Head, pp 1483–1485

    Google Scholar 

  158. Tan W-H, Takeuchi S (2006) An optical retrieval microfluidic system for microarray applications. In: Proceedings MicroTAS2006, Tokyo, 5–9 Nov 2006. Transducer Research Foundation, Hilton Head, pp 509–511

    Google Scholar 

  159. Tan W-H, Takeuchi S (2007) A trap-and-release integrated microfluidic system for dynamic microarray applications. Proc Natl Acad Sci USA 104(4):1146–1151

    Article  CAS  Google Scholar 

  160. Chabert M et al. (2006) Automated microdroplet platform for sample manipulation and polymerase chain reaction. Anal Chem 78:7722–7728

    Article  CAS  Google Scholar 

  161. Diehl F et al. (2006) BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions. Nat Methods 3(7):551–559

    Article  CAS  Google Scholar 

  162. Kojima T et al. (2005) PCR amplification from single DNA molecules on magnetic beads in emulsion: application for high-throughput screening of transcription factor targets. Nucleic Acids Res 33:e150

    Article  Google Scholar 

  163. Musyanovych A, Mailander V, Landfester K (2005) Miniemulsion droplets as single molecule nanoreactors for polymerase chain reaction. Biomacromolecules 6:1824–1828

    Article  CAS  Google Scholar 

  164. Li M et al. (2006) BEAMing up for detection and quantification of rare sequence variants. Nat Methods 3(2):95–97

    Article  CAS  Google Scholar 

  165. Dorfman KD et al. (2005) Contamination-free continuous flow microfluidic polymerase chain reaction for quantitative and clinical applications. Anal Chem 77:3700–3704

    Article  CAS  Google Scholar 

  166. Gonzalez A et al. (2007) Gene transcript amplification from cell lysates in continuous-flow microfluidic devices. Biomed Microdev 9:729–736

    Article  CAS  Google Scholar 

  167. Liau A et al. (2005) Mixing crowded biological solutions in milliseconds. Anal Chem 77:7618–7625

    Article  CAS  Google Scholar 

  168. Zheng B, Tice JD, Ismagilov RF (2004) Formation of droplets of alternating composition in microfluidic channels and applications to indexing of concentrations in droplet-based assays. Anal Chem 76:4977–4982

    Article  CAS  Google Scholar 

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Correspondence to Yonggang Zhu .

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Meike Werther Harald Seitz

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Zhu, Y., Power, B.E. (2008). Lab-on-a-chip in Vitro Compartmentalization Technologies for Protein Studies. In: Werther, M., Seitz, H. (eds) Protein – Protein Interaction. Advances in Biochemical Engineering/Biotechnology, vol 110. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2008_098

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