1932

Abstract

This review compares droplet-based microfluidic systems used to study crystallization fundamentals in chemistry and biology. An original high-throughput droplet-based microfluidic platform is presented. It uses nanoliter droplets, generates a chemical library, and directly solubilizes powder, thus economizing both material and time. It is compatible with all solvents without the need for surfactant. Its flexibility permits phase diagram determination and crystallization studies (screening and optimizing experiments) and makes it easy to use for nonspecialists in microfluidics. Moreover, it allows concentration measurement via ultraviolet spectroscopy and solid characterization via X-ray diffraction analysis.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-chembioeng-060718-030312
2019-06-07
2024-10-03
Loading full text...

Full text loading...

/deliver/fulltext/chembioeng/10/1/annurev-chembioeng-060718-030312.html?itemId=/content/journals/10.1146/annurev-chembioeng-060718-030312&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Veesler S, Puel F. 2015. Crystallization of pharmaceutical crystals. Handbook of Crystal Growth T Nishinaga 915–49 Boston: Elsevier, 2nd ed..
    [Google Scholar]
  2. 2.
    Candoni N, Grossier R, Hammadi Z, Morin R, Veesler S 2012. Practical physics behind growing crystals of biological macromolecules. Protein Peptide Lett 19:714–24
    [Google Scholar]
  3. 3.
    Mangin D, Puel F, Veesler S 2009. Polymorphism in processes of crystallization in solution: a practical review. Org. Process Res. Dev. 13:1241–53
    [Google Scholar]
  4. 4.
    Kashchiev D. 2000. Nucleation: Basic Theory with Applications Oxford, UK: Butterworth-Heinemann529
    [Google Scholar]
  5. 5.
    Galkin O, Vekilov PG. 2000. Are nucleation kinetics of protein crystals similar to those of liquid droplets?. J. Am. Chem. Soc. 122:156–63
    [Google Scholar]
  6. 6.
    Hammadi Z, Grossier R, Zhang S, Ikni A, Candoni N et al. 2015. Localizing and inducing primary nucleation. Faraday Discuss 179:489–501
    [Google Scholar]
  7. 7.
    Jiang S, ter Horst JH 2011. Crystal nucleation rates from probability distributions of induction times. Cryst. Growth Des. 11:256–61
    [Google Scholar]
  8. 8.
    Svärd M, Nordström FL, Jasnobulka T, Rasmuson ÅC 2009. Thermodynamics and nucleation kinetics of m-aminobenzoic acid polymorphs. Cryst. Growth Des. 10:195–204
    [Google Scholar]
  9. 9.
    Li L, Mustafi D, Fu Q, Tereshko V, Chen DL et al. 2006. Nanoliter microfluidic hybrid method for simultaneous screening and optimization validated with crystallization of membrane proteins. PNAS 103:19243–48
    [Google Scholar]
  10. 10.
    Shim J-U, Cristobal G, Link DR, Thorsen T, Fraden S 2007. Using microfluidics to decouple nucleation and growth of protein. Cryst. Growth Des. 7:2192–94
    [Google Scholar]
  11. 11.
    Squires TM, Quake SR. 2005. Microfluidics: fluid physics at the nanoliter scale. Rev. Mod. Phys. 77:977
    [Google Scholar]
  12. 12.
    Dombrowski RD, Litster JD, Wagner NJ, He Y 2007. Crystallization of alpha-lactose monohydrate in a drop-based microfluidic crystallizer. Chem. Eng. Sci. 62:4802–10
    [Google Scholar]
  13. 13.
    Hansen CL, Skordalakes E, Berger JM, Quake SR 2002. A robust and scalable microfluidic metering method that allows protein crystal growth by free interface diffusion. PNAS 99:16531–36
    [Google Scholar]
  14. 14.
    Perry SL, Guha S, Pawate AS, Bhaskarla A, Agarwal V et al. 2013. A microfluidic approach for protein structure determination at room temperature via on-chip anomalous diffraction. Lab Chip 13:3183–87
    [Google Scholar]
  15. 15.
    Dhouib K, Malek CK, Pfleging W, Gauthier-Manuel B, Duffait R et al. 2009. Microfluidic chips for the crystallization of biomacromolecules by counter-diffusion and on-chip crystal X-ray analysis. Lab Chip 9:1412–21
    [Google Scholar]
  16. 16.
    Otálora F, Gavira JA, Ng JD, García-Ruiz JM 2009. Counterdiffusion methods applied to protein crystallization. Prog. Biophys. Mol. Biol. 101:26–37
    [Google Scholar]
  17. 17.
    Li L, Ismagilov RF. 2010. Protein crystallization using microfluidic technologies based on valves, droplets, and SlipChip. Annu. Rev. Biophys. 39:139–58
    [Google Scholar]
  18. 18.
    Zheng B, Gerdts CJ, Ismagilov RF 2005. Using nanoliter plugs in microfluidics to facilitate and understand protein crystallization. Curr. Opin. Struct. Biol. 15:548–55
    [Google Scholar]
  19. 19.
    Gerdts CJ, Elliott M, Lovell S, Mixon MB, Napuli AJ et al. 2008. The plug-based nanovolume Microcapillary Protein Crystallization System (MPCS). Acta Crystallogr. D 64:1116–22
    [Google Scholar]
  20. 20.
    Ildefonso M, Candoni N, Veesler S 2012. A cheap, easy microfluidic crystallization device ensuring universal solvent compatibility. Org. Process Res. Dev. 16:556–60
    [Google Scholar]
  21. 21.
    Ildefonso M, Revalor E, Punniam P, Salmon JB, Candoni N, Veesler S 2012. Nucleation and polymorphism explored via an easy-to-use microfluidic tool. J. Cryst. Growth 342:9–12
    [Google Scholar]
  22. 22.
    Zhang S, Ferté N, Candoni N, Veesler S 2015. Versatile microfluidic approach to crystallization. Org. Process Res. Dev. 19:1837–41
    [Google Scholar]
  23. 23.
    Candoni N, Hammadi Z, Grossier R, Ildefonso M, Morin R, Veesler S 2015. Addressing the stochasticity of nucleation: practical approaches. Advances in Organic Crystal Chemistry R Tamura, M Miyata 95–113 Tokyo: Springer
    [Google Scholar]
  24. 24.
    Whitesides GM. 2006. The origins and the future of microfluidics. Nature 442:368–73
    [Google Scholar]
  25. 25.
    Beebe DJ, Moore JS, Bauer JM, Yu Q, Liu RH et al. 2000. Functional hydrogel structures for autonomous flow control inside microfluidic channels. Nature 404:588–90
    [Google Scholar]
  26. 26.
    Unger MA, Chou H-P, Thorsen T, Scherer A, Quake SR 2000. Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 288:113–16
    [Google Scholar]
  27. 27.
    McDonald JC, Whitesides GM. 2002. Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. Acc. Chem. Res. 35:491–99
    [Google Scholar]
  28. 28.
    Zhang S, Gerard CJJ, Ikni A, Ferry G, Vuillard LM et al. 2017. Microfluidic platform for optimization of crystallization conditions. J. Cryst. Growth 472:18–28
    [Google Scholar]
  29. 29.
    Gerard CJJ, Ferry G, Vuillard LM, Boutin JA, Ferte N et al. 2018. A chemical library to screen protein and protein–ligand crystallization using a versatile microfluidic platform. Cryst. Growth Des. 18:5130–37
    [Google Scholar]
  30. 30.
    Ildefonso M, Candoni N, Veesler S 2013. Heterogeneous nucleation in droplet-based nucleation measurements. Cryst. Growth Des. 13:2107–10
    [Google Scholar]
  31. 31.
    Gerard CJJ, Ferry G, Vuillard LM, Boutin JA, Chavas LMG et al. 2017. Crystallization via tubing microfluidics permits both in situ and ex situ X-ray diffraction. Acta Crystallogr. Sect. F 73:574–78
    [Google Scholar]
  32. 32.
    Ildefonso M, Candoni N, Veesler S 2011. Using microfluidics for fast, accurate measurement of lysozyme nucleation kinetics. Cryst. Growth Des. 11:1527–30
    [Google Scholar]
  33. 33.
    Peybernès G, Grossier R, Villard F, Letellier P, Lagaize M et al. 2018. Microfluidics setup rapidly measures solubility directly from powder. Org. Process Res. Dev. 22:1856–60
    [Google Scholar]
  34. 34.
    Garstecki P, Fuerstman MJ, Stone HA, Whitesides GM 2006. Formation of droplets and bubbles in a microfluidic T-junction-scaling and mechanism of break-up. Lab Chip 6:437–46
    [Google Scholar]
  35. 35.
    Xu JH, Li SW, Tan J, Luo GS 2008. Correlations of droplet formation in T-junction microfluidic devices: from squeezing to dripping. Microfluid. Nanofluidics 5:711–17
    [Google Scholar]
  36. 36.
    Christopher GF, Noharuddin NN, Taylor JA, Anna SL 2008. Experimental observations of the squeezing-to-dripping transition in T-shaped microfluidic junctions. Phys. Rev. E 78:036317
    [Google Scholar]
  37. 37.
    Liu H, Zhang Y. 2009. Droplet formation in a T-shaped microfluidic junction. J. Appl. Phys. 106:034906
    [Google Scholar]
  38. 38.
    Gupta A, Kumar R. 2010. Flow regime transition at high capillary numbers in a microfluidic T-junction: viscosity contrast and geometry effect. Phys. Fluids 22:122001
    [Google Scholar]
  39. 39.
    Glawdel T, Elbuken C, Ren CL 2012. Droplet formation in microfluidic T-junction generators operating in the transitional regime. I. Experimental observations. Phys. Rev. E 85:016322
    [Google Scholar]
  40. 40.
    Glawdel T, Elbuken C, Ren CL 2012. Droplet formation in microfluidic T-junction generators operating in the transitional regime. II. Modeling. Phys. Rev. E 85:016323
    [Google Scholar]
  41. 41.
    Wehking J, Gabany M, Chew L, Kumar R 2013. Effects of viscosity, interfacial tension, and flow geometry on droplet formation in a microfluidic T-junction. Microfluid. Nanofluidics 16:441–53
    [Google Scholar]
  42. 42.
    Thorsen T, Roberts RW, Arnold FH, Quake SR 2001. Dynamic pattern formation in a vesicle-generating microfluidic device. Phys. Rev. Lett. 86:4163–66
    [Google Scholar]
  43. 43.
    van Steijn V, Kleijn CR, Kreutzer MT 2010. Predictive model for the size of bubbles and droplets created in microfluidic T-junctions. Lab Chip 10:2513–18
    [Google Scholar]
  44. 44.
    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
    [Google Scholar]
  45. 45.
    Tice JD, Song H, Lyon AD, Ismagilov RF 2003. Formation of droplets and mixing in multiphase microfluidics at low values of the Reynolds and the capillary numbers. Langmuir 19:9127–33
    [Google Scholar]
  46. 46.
    Zhao C-X, Middelberg APJ. 2011. Two-phase microfluidic flows. Chem. Eng. Sci. 66:1394–411
    [Google Scholar]
  47. 47.
    Chen N, Wu J, Jiang H, Dong L 2011. CFD simulation of droplet formation in a wide-type microfluidic T-junction. J. Dispers. Sci. Technol. 33:1635–41
    [Google Scholar]
  48. 48.
    Zhang S, Guivier-Curien C, Veesler S, Candoni N 2015. Prediction of sizes and frequencies of nanoliter-sized droplets in cylindrical T-junction microfluidics. Chem. Eng. Sci. 138:128–39
    [Google Scholar]
  49. 49.
    Song H, Bringer MR, Tice JD, Gerdts CJ, Ismagilov RF 2003. Experimental test of scaling of mixing by chaotic advection in droplets moving through microfluidic channels. Appl. Phys. Lett. 83:4664–66
    [Google Scholar]
  50. 50.
    Trivedi V, Doshi A, Kurup GK, Ereifej E, Vandevord PJ, Basu AS 2010. A modular approach for the generation, storage, mixing, and detection of droplet libraries for high throughput screening. Lab Chip 10:2433–42
    [Google Scholar]
  51. 51.
    Baroud CN, Gallaire F, Dangla R 2010. Dynamics of microfluidic droplets. Lab Chip 10:2032–45
    [Google Scholar]
  52. 52.
    Chayen NE, Shaw Stewart PD, Maeder DL, Blow DM 1990. An automated system for micro-batch protein crystallization and screening. J. Appl. Crystallogr. 23:297–302
    [Google Scholar]
  53. 53.
    Candoni N, Hammadi Z, Grossier R, Ildefonso M, Revalor E et al. 2012. Nanotechnologies dedicated to nucleation control. Int. J. Nanotechnol. 9:439–59
    [Google Scholar]
  54. 54.
    Dunuwila DD, Berglund KA. 1997. ATR FTIR spectroscopy for in situ measurement of supersaturation. J. Cryst. Growth 179:185–93
    [Google Scholar]
  55. 55.
    Lewiner F, Klein JP, Puel F, Févotte G 2001. On-line ATR FTIR measurement of supersaturation during solution crystallization processes. Calibration and applications on three solute/solvent systems. Chem. Eng. Sci. 56:2069–84
    [Google Scholar]
  56. 56.
    Schwartz AM, Berglund KA. 1999. The use of Raman spectroscopy for in situ monitoring of lysozyme concentration during crystallization in a hanging drop. J. Cryst. Growth 203:599–603
    [Google Scholar]
  57. 57.
    Laval P, Lisai N, Salmon JB, Joanicot M 2007. A microfluidic device based on droplet storage for screening solubility diagrams. Lab Chip 7:829–34
    [Google Scholar]
  58. 58.
    Leng J, Salmon JB. 2009. Microfluidic crystallization. Lab Chip 9:24–34
    [Google Scholar]
  59. 59.
    Bustamante P, Romero S, Peña A, Escalera B, Reillo A 1998. Enthalpy–entropy compensation for the solubility of drugs in solvent mixtures: paracetamol, acetanilide, and nalidixic acid in dioxane–water. J. Pharm. Sci. 87:1590–96
    [Google Scholar]
  60. 60.
    Hojjati H, Rohani S. 2006. Measurement and prediction of solubility of paracetamol in water−isopropanol solution. Part 1. Measurement and data analysis. Org. Process Res. Dev. 10:1101–9
    [Google Scholar]
  61. 61.
    Granberg RA, Rasmuson ÅC 1999. Solubility of paracetamol in pure solvents. J. Chem. Eng. Data 44:1391–95
    [Google Scholar]
  62. 62.
    Nagai T, Prakongpan S. 1984. Solubility of acetaminophen in cosolvents. Chem. Pharm. Bull. 32:340–43
    [Google Scholar]
  63. 63.
    Bustamante P, Romero S, Reillo A 1995. Thermodynamics of paracetamol in amphiprotic and amphiprotic-aprotic solvent mixtures. Pharm. Sci. 1:505–7
    [Google Scholar]
  64. 64.
    Jouyban A, Chan H-K, Chew NYK, Khoubnasabjafari M, Acree WE Jr 2006. Solubility prediction of paracetamol in binary and ternary solvent mixtures using Jouyban–Acree model. Chem. Pharm. Bull. 54:428–31
    [Google Scholar]
  65. 65.
    Jiménez JA, Martínez F. 2006. Thermodynamic study of the solubility of acetaminophen in propylene glycol + water cosolvent mixtures. J. Braz. Chem. Soc. 17:125–34
    [Google Scholar]
  66. 66.
    Detoisien T, Forite M, Taulelle P, Teston J, Colson D et al. 2009. A rapid method for screening crystallization conditions and phases of an active pharmaceutical ingredient. Org. Process Res. Dev. 13:1338–42
    [Google Scholar]
  67. 67.
    Kashchiev D, Verdoes D, Van Rosmalen GM 1991. Induction time and metastability limit in new phase formation. J. Cryst. Growth 110:373–80
    [Google Scholar]
  68. 68.
    Revalor E, Hammadi Z, Astier JP, Grossier R, Garcia E et al. 2010. Usual and unusual crystallization from solution. J. Cryst. Growth 312:939–46
    [Google Scholar]
  69. 69.
    Ostwald W. 1897. Studien uber die bildung und umwandlund fester korper. Z. Phys. Chem. 22:289–330
    [Google Scholar]
  70. 70.
    Ataka M, Asai M. 1988. Systematic studies on the crystallization of lysozyme. J. Cryst. Growth 90:86–93
    [Google Scholar]
  71. 71.
    Legrand L, Ries-Kautt M, Robert M-C 2002. Two polymorphs of lysozyme nitrate: temperature dependence of their solubility. Acta Crystallogr. D 58:1564–67
    [Google Scholar]
  72. 72.
    Astier JP, Veesler S. 2008. Using temperature to crystallize proteins: a mini-review. Cryst. Growth Des. 8:4215–19
    [Google Scholar]
  73. 73.
    Lee AY, Lee IS, Myerson AS 2006. Factors affecting the polymorphic outcome of glycine crystals constrained on patterned substrates. Chem. Eng. Technol. 29:281–85
    [Google Scholar]
  74. 74.
    Laval P, Giroux C, Leng J, Salmon J-B 2008. Microfluidic screening of potassium nitrate polymorphism. J. Cryst. Growth 310:3121–24
    [Google Scholar]
  75. 75.
    Vivares D, Veesler S, Astier JP, Bonneté F 2006. Polymorphism of urate oxidase in PEG solutions. Cryst. Growth Des. 6:287–92
    [Google Scholar]
  76. 76.
    Tsekova D, Dimitrova S, Nanev CN 1999. Heterogeneous nucleation (and adhesion) of lysozyme crystals. J. Cryst. Growth 196:226–33
    [Google Scholar]
  77. 77.
    Galkin O, Vekilov PG. 1999. Direct determination of the nucleation rates of protein crystals. J. Phys. Chem. B 103:10965–71
    [Google Scholar]
  78. 78.
    Selimovic S, Jia Y, Fraden S 2009. Measuring the nucleation rate of lysozyme using microfluidics. Cryst. Growth Des. 9:1806–10
    [Google Scholar]
  79. 79.
    Grossier R, Magnaldo A, Veesler S 2010. Ultra-fast crystallization due to confinement. J. Cryst. Growth 312:487–89
    [Google Scholar]
  80. 80.
    Grossier R, Veesler S. 2009. Reaching one single and stable critical cluster through finite sized systems. Cryst. Growth Des. 9:1917–22
    [Google Scholar]
  81. 81.
    Gibbs J. 1948. The Collected Works 1 Thermodynamics New Haven, CT: Yale Univ. Press
    [Google Scholar]
  82. 82.
    Chayen NE. 1996. A novel technique for containerless protein crystallization. Protein Eng 9:927–29
    [Google Scholar]
  83. 83.
    Song H, Chen DL, Ismagilov RF 2006. Reactions in droplets in microfluidic channels. Angew. Chem. Int. Ed. 45:7336–56
    [Google Scholar]
  84. 84.
    Song H, Tice JD, Ismagilov RF 2003. A microfluidic system for controlling reaction networks in time. Angew. Chem. Int. Ed. 42:768–72
    [Google Scholar]
  85. 85.
    Poe SL, Cummings MA, Haaf MP, McQuade DT 2006. Solving the clogging problem: precipitate-forming reactions in flow. Angew. Chem. Int. Ed. 45:1544–48
    [Google Scholar]
  86. 86.
    Zheng B, Roach LS, Ismagilov RF 2003. Screening of protein crystallization conditions on a microfluidic chip using nanoliter-size droplets. J. Am. Chem. Soc. 125:11170–71
    [Google Scholar]
  87. 87.
    Blundell TL, Jhoti H, Abell C 2002. High-throughput crystallography for lead discovery in drug design. Nat. Rev. Drug Discov. 1:45–54
    [Google Scholar]
  88. 88.
    Mande SC, Sobhia ME. 2000. Structural characterization of protein–denaturant interactions: crystal structures of hen egg-white lysozyme in complex with DMSO and guanidinium chloride. Protein Eng. Des. Select. 13:133–41
    [Google Scholar]
  89. 89.
    Maeki M, Yamaguchi H, Tokeshi M, Miyazaki M 2016. Microfluidic approaches for protein crystal structure analysis. Anal. Sci. 32:3–9
    [Google Scholar]
  90. 90.
    Stojanoff V, Jakoncic J, Oren DA, Nagarajan V, Navarro Poulsen J-C et al. 2011. From screen to structure with a harvestable microfluidic device. Acta Crystallogr. F 67:971–75
    [Google Scholar]
  91. 91.
    Guha S, Perry SL, Pawate AS, Kenis PJA 2012. Fabrication of X-ray compatible microfluidic platforms for protein crystallization. Sensors Actuators B 174:1–9
    [Google Scholar]
  92. 92.
    Pinker F, Brun M, Morin P, Deman A-L, Chateaux J-F et al. 2013. ChipX: a novel microfluidic chip for counter-diffusion crystallization of biomolecules and in situ crystal analysis at room temperature. Cryst. Growth Des. 13:3333–40
    [Google Scholar]
  93. 93.
    Khvostichenko DS, Schieferstein JM, Pawate AS, Laible PD, Kenis PJA 2014. X-ray transparent microfluidic chip for mesophase-based crystallization of membrane proteins and on-chip structure determination. Crystal Growth Des 14:4886–90
    [Google Scholar]
  94. 94.
    Horstman EM, Goyal S, Pawate A, Lee G, Zhang GGZ et al. 2015. Crystallization optimization of pharmaceutical solid forms with X-ray compatible microfluidic platforms. Crystal Growth Des 15:1201–9
    [Google Scholar]
  95. 95.
    Heymann M, Opathalage A, Wierman JL, Akella S, Szebenyi DME et al. 2015. Room-temperature serial crystallography using a kinetically optimized microfluidic device for protein crystallization and on-chip X-ray diffraction. Corrigendum. IUCrJ 2:601
    [Google Scholar]
  96. 96.
    Maeki M, Pawate AS, Yamashita K, Kawamoto M, Tokeshi M et al. 2015. A method of cryoprotection for protein crystallography by using a microfluidic chip and its application for in situ X-ray diffraction measurements. Anal. Chem. 87:4194–200
    [Google Scholar]
  97. 97.
    Sui S, Perry SL. 2017. Microfluidics: from crystallization to serial time-resolved crystallography. Struct. Dyn. 4:032202
    [Google Scholar]
  98. 98.
    Yadav MK, Gerdts CJ, Sanishvili R, Smith WW, Roach LS et al. 2005. In situ data collection and structure refinement from microcapillary protein crystallization. J. Appl. Crystallogr. 38:900–5
    [Google Scholar]
  99. 99.
    Maeki M, Yoshizuka S, Yamaguchi H, Kawamoto M, Yamashita K et al. 2012. X-ray diffraction of protein crystal grown in a nano-liter scale droplet in a microchannel and evaluation of its applicability. Anal. Sci. 28:65
    [Google Scholar]
  100. 100.
    Gerdts CJ, Stahl GL, Napuli A, Staker B, Abendroth J et al. 2010. Nanovolume optimization of protein crystal growth using the microcapillary protein crystallization system. J. Appl. Crystallogr. 43:1078–83
    [Google Scholar]
  101. 101.
    Foster CE, Bianchet MA, Talalay P, Zhao Q, Amzel LM 1999. Crystal structure of human quinone reductase type 2, a metalloflavoprotein. Biochemistry 38:9881–86
    [Google Scholar]
  102. 102.
    Grossier R, Hammadi Z, Morin R, Magnaldo A, Veesler S 2011. Generating nanoliter to femtoliter microdroplets with ease. Appl. Phys. Lett. 98:091916
    [Google Scholar]
/content/journals/10.1146/annurev-chembioeng-060718-030312
Loading
/content/journals/10.1146/annurev-chembioeng-060718-030312
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error