Abstract：The recent advances in crystallization and polymerization assisted by droplet-based microfluidics to synthesize micro-particles and micro-crystals are reviewed in this paper. Droplet-based microfluidic devices are powerful tools to execute some precise controls and operations on the flow inside microchannels by adjusting fluid dynamics parameters to produce monodisperse emulsions or multiple-emulsions of various materials. Major features of this technique are producing particles of monodispersity to control the shape of particles in a new level, and to generate droplets of diverse materials including aqueous solutions, gels and polymers. Numerous microfluidic devices have been employed to generate monodisperse droplets of range from nm to μm, such as T junctions, flow-focusing devices and co-flow or cross-flow capillaries. These discrete, independently controllable droplets are ideal microreactors to be manipulated in the channels to synthesize the nanocrystals, protein crystals, polymer particles and microcapsules. The generated monodisperse particles or crystals are to meet different technical demands in many fields, such as crystal engineering, encapsulation and drug delivery systems. Microfluidic devices are promising tools in the synthesis of micron polymer particles that have diverse applications such as the photonic materials, ion-exchange and chromatography columns, and field-responsive rheological fluids. Processes assisted by microfluidic devices are able to produce the polymer particles (including Janus particles) with precise control over their sizes, size distribution, morphology and compositions. The technology of microfluidics has also been employed to generate core-shell microcapsules and solid microgels with precise controlled sizes and inner structures. The chosen “smart” materials are sensitive to an external stimulus such as the change of the pH, electric field and temperature. These complex particles are also able to be functionalized by encapsulating nanoparticles of special functions and by attaching some special groups like targeting ligands. The nucleation kinetics of some crystals like KNO3 was investigated in different microfluidic devices. Because of the elimination of the interactions among crystallites in bulk systems, using independent droplets may help to measure the nucleation rate more accurately. In structural biology, the droplets produced in microfluidic devices provide ideal platforms for protein crystallization on the nanoliter scale. Therefore, they become one of the promising tools to screen the optimal conditions of protein crystallization.
出版日期: 2010-03-05
引用本文:
. Synthesis of crystals and particles by crystallization
and polymerization in droplet-based microfluidic devices[J]. Front. Chem. Sci. Eng., 2010, 4(1): 26-36.
Jingtao WANG, Jin ZHANG, Junjie HAN, . Synthesis of crystals and particles by crystallization
and polymerization in droplet-based microfluidic devices. Front. Chem. Sci. Eng., 2010, 4(1): 26-36.
Glotzer S C, Solomon M J. Anisotropy of building blocksand their assembly into complex structures. Nature materials, 2007, 6: 557―562 doi: 10.1038/nmat1949
Oh J K, Drumright R, Siegwartb D J, Matyjaszewski K. The development of microgels/nanogels for drug delivery applications. Prog Polym Sci, 2008, 33: 448―477 doi: 10.1016/j.progpolymsci.2008.01.002
Utada A S, Chu L Y, Fernandez-Nieves A, Link D R, Holtze C, Weitz D A. Dripping, jetting, drops, and wetting the magic of microfluidics. MRS Bull, 2007, 32: 702―708
Serra1 C A, Chang Z Q. Microfluidic-assisted synthesisof polymer particles. Chem Eng Technol, 2008, 31(8): 1099―1115 doi: 10.1002/ceat.200800219
Link D R, Anna S L, Weitz D A, Stone H A. Geometricallymediated breakup of drops in microfluidic devices. Phys Rev Lett, 2004, 92: 054503-1―054503-4
Kawakatsu T, Kikuchi Y, Nakajima M. Regular-sized cell creation in microchannel emulsificationby visual microprocessing method. J AmOil Chem Soc, 1997, 74(3): 317―321 doi: 10.1007/s11746-997-0143-8
Thorsen T, Roberts R W, Arnold F H, Quake S R. Dynamicpattern formation in a vesicle-generating microfluidic device. Phys Rev Lett, 2001, 86: 4163―4166 doi: 10.1103/PhysRevLett.86.4163
Anna S L, Bontoux N, Stone H A. Formation of dispersions using ‘‘flow focusing’’in microchannels. Appl Phys Lett, 2003, 82: 364―366 doi: 10.1063/1.1537519
Jeong W J, Kim J Y, Choo J, Lee E K, Han C S, Beebe D J, Seong G H, Lee S H. Continuous fabrication of biocatalyst immobilized microparticlesusing photopolymerization and immiscible liquids in microfluidic systems. Langmuir, 2005, 21: 3738―3741 doi: 10.1021/la050105l
Quevedo E, Steinbacher J, McQuade D T. Interfacial polymerization within a simplified microfluidicdevice: capturing capsules. J Am Chem Soc, 2005, 127: 10498―10499 doi: 10.1021/ja0529945
Takeuchi S, Garstecki P, Weibel D B, Whitesides G M. An axisymmetric flow-focusing microfluidic device. Adv Mater, 2005, 17(8): 1067―1072 doi: 10.1002/adma.200401738
Shah R K, Shum H C, Rowat A C, Lee D Y, Agresti J J, Utada A S, Chu L Y, Kim J W, Alberto F N, Martinez C J, Weitz D A. Designer emulsions using microfluidics. Materials Today, 2008, 11: 18―27 doi: 10.1016/S1369-7021(08)70053-1
Engl W, Backov R, Panizza P. Controlled production of emulsions and particles by milli-and microfluidic techniques. Current Opinionin Colloid & Interface Science, 2008, 13: 206―216 doi: 10.1016/j.cocis.2007.09.003
Okushima S, Nisisako T, Torii T, Higuchi T. Controlled production of monodisperse double emulsions by two-stepdroplet break-up in microfluidic devices. Langmuir, 2004, 20: 9905―9908 doi: 10.1021/la0480336
Seo M, Paquet C, Nie Z H, Xu S Q, Kumacheva E. Microfluidic consecutiveflow-focusing droplet generators. SoftMatter, 2007, 3: 986―992 doi: 10.1039/b700687j
Utada A S, Lorenceau E, Link D R, Kaplan P D, Stone H A, Weitz D A. Monodisperse double emulsions generated from a microcapillary device. Science, 2005, 308: 537―541 doi: 10.1126/science.1109164
Nie Z H, Xu S Q, Seo M, Lewis P C, KumachevaE. Polymer particles with various shapes and morphologies producedin continuous microfluidic reactors. JAm Chem Soc, 2005, 127: 8058―8063 doi: 10.1021/ja042494w
Chu L Y, Utada A S, Shah R K, Kim J W, Weitz D A. Controllable monodisperse multiple emulsions. Angew Chem Int Ed, 2007, 46: 8970―8974 doi: 10.1002/anie.200701358
Panizza P, Engl W, Hany C, Backov R. Controlledproduction of hierarchically organized large emulsions and particlesusing assemblies on line of coaxial flow devices. Colloids Surf, A Physicochem Eng Asp, 2008, 312: 24―31 doi: 10.1016/j.colsurfa.2007.06.026
Nisisako T, Torii T, Higuchi T. Novel microreactors for functional polymer beads. Chem Eng J, 2004, 101: 23―29 doi: 10.1016/j.cej.2003.11.019
Dendukuri D, Tsoi K, Hatton T A, Doyle P S. Controlledsynthesis of nonspherical microparticles using microfluidics. Langmuir, 2005, 21: 2113―2116 doi: 10.1021/la047368k
Xu S Q, Nie Z, Seo M, Lewis P, Kumacheva E, Stone H A, Garstecki P, Weibel D B, Gitlin I, Whitesides G M. Generation of monodisperse particles by using microfluidics: controlover size, shape and composition. AngewChem Int Ed, 2005, 44: 724―728 doi: 10.1002/anie.200462226
Lewis P C, Graham R R, Nie Z H, Xu S Q, Seo M, Kumacheva E. Continuous synthesis of copolymer particles in microfluidic reactors. Macromolecules, 2005, 38: 4536―4538 doi: 10.1021/ma050101n
Seo M, Nie Z H, Xu S Q, Mok M, Lewis P C, Graham R R, Kumacheva E. Continuous microfluidic reactorsfor polymer particles. Langmuir, 2005, 21: 11614―11622 doi: 10.1021/la050519e
Dubinsky S, Zhang H, Nie Z H, Gourevich I, Voicu D, Deetz M, Kumacheva E, Microfluidic synthesis of macroporous copolymer particles. Macromolecules, 2008, 41: 3555―3561 doi: 10.1021/ma800300d
Jeong, W, Kim J Y, Kim S J, Lee S H, Mensing G, Beebe D J. Hydrodynamic microfabrication via “on the fly” photopolymerizationof microscale fibers and tubes. Lab chip, 2004, 4: 576―580 doi: 10.1039/b411249k
Engl W, Tachibana M, Panizza P, Backov R. Millifluidicas a versatile reactor to tune size and aspect ratio of large polymerizedobjects. International Journal of MultiphaseFlow, 2007, 33: 897―903 doi: 10.1016/j.ijmultiphaseflow.2007.03.007
Perro A, Reculusa S, Ravaine S, Bourgeat-Lami E, Duguet E. Design and synthesis of Janusmicro- and nanoparticles. J Mater Chem, 2005, 15: 3745―3760 doi: 10.1039/b505099e
Nisisako T, Torii T, Takahashi T, Takizawa Y. Synthesis of monodisperse bicolored Janus particles with electricalanisotropy using a microfluidic co-flow system. Adv Mater, 2006, 18: 1152―1156 doi: 10.1002/adma.200502431
Nisisako T, Torii T. Formation of biphasic Janusdroplets in a microfabricated channel for the synthesis of shape-controlledpolymer microparticles. Adv Mater, 2007, 19: 1489―1493 doi: 10.1002/adma.200700272
Nie Z, Li W, Seo M, Xu S Q, Kumacheva E. Janus and ternary particlesgenerated by microfluidic synthesis: design, synthesis, and self-assembly. J Am Chem Soc, 2006, 128: 9408―9412 doi: 10.1021/ja060882n
Shepherd R F, Conrad J C, Rhodes S K, Link D R, Marquez M, Weitz D A, Lewis J A. Microfluidic assembly ofhomogeneous and Janus colloid-filled hydrogel granules. Langmuir, 2006, 22: 8618―8622 doi: 10.1021/la060759+
Kim S H, Jeon S J, Jeong W C, Park H S, Yang S M. Optofluidic synthesis of electroresponsivephotonic Janus balls with isotropic structural colors. Adv Mater, 2008, 20: 4129―4134
Shah R K, Kim J W, Weitz D A. Janus supraparticles by induced phase separation of nanoparticlesin droplets. Adv Mater, 2009, 21: 1949―1953 doi: 10.1002/adma.200803115
Chen C H, Shah R K, Abate A R, Weitz D A. Janus particlestemplated from double Emulsion droplets generated using microfluidics. Langmuir, 2009, 25(8): 4320―4323 doi: 10.1021/la900240y
Gong X Q, Peng S L, Wen W J, Sheng P, Li W H. Design and fabrication of magneticallyfunctionalized core/shell microspheres for smart drug delivery. Adv Funct Mater, 2009, 19: 292―297 doi: 10.1002/adfm.200801315
Eun T H, Kim S H, Jeong W J, Jeon S J, Kim S H, Yang S M. Single-step fabrication of monodisperse TiO2 hollow spheres with embedded nanoparticles in microfluidic devices. Chem Mater, 2009, 21: 201―203 doi: 10.1021/cm8017133
Geest B G De, Urbanski J P, Thorsen T, Demeester J, De Smedt S C. Synthesis of monodispersebiodegradable microgels in microfluidic devices. Langmuir, 2005, 21: 10275―10279 doi: 10.1021/la051527y
Kim J W, Utada A S, Fernandez-Nieves A, Hu Z B, Weitz D A. Fabrication of monodispersegel shells and functional microgels in microfluidic devices. Angew Chem Int Ed, 2007, 46: 1819―1822 doi: 10.1002/anie.200604206
Chang J Y, Yang C H, Huang K S. Microfluidic assisted preparation of CdSe/ZnS nanocrystalsencapsulated into poly(DL-lactide-co-glycolide)microcapsules. Nanotechnology, 2007, 18: 305305-1―305305-8
Chu L Y, Kim J W, Shah R K, Weitz D A. Monodispersethermoresponsive microgels with tunable volume-phase transition kinetics. Adv Funct Mater, 2007, 17: 3499―3504 doi: 10.1002/adfm.200700379
Zhang H, Tumarkin E, Peerani R, Nie Z H, Sullan R M A, Walker G C, Kumacheva E. Microfluidicproduction of biopolymer microcapsules with controlled morphology. J Am Chem Soc, 2006, 128: 12205―12210 doi: 10.1021/ja0635682
Tan W H, Takeuchi S. Monodisperse alginate hydrogelmicrobeads for cell encapsulation. AdvMater, 2007, 19: 2696―2701 doi: 10.1002/adma.200700433
Zhang H, Tumarkin E, Sullan R M A, Walker G C, Kumacheva E. Exploring microfluidic routesto microgels of biological polymers. MacromolRapid Commun, 2007, 28: 527―538 doi: 10.1002/marc.200600776
Liu K, Ding H J, Liu J, Chen Y, Zhao X Z. Shape-controlled production of biodegradablecalcium alginate gel microparticles using a novel microfluidic device. Langmuir, 2006, 22: 9453―9457 doi: 10.1021/la061729+
Rondeau E, Cooper-White J J. Biopolymer microparticleand nanoparticle formation within a microfluidic device. Langmuir, 2008, 24: 6937―6945 doi: 10.1021/la703339u
Xu J H, Li S W, Tan J, Luo G S. Controllablepreparation of monodispersed calcium alginate microbeads in a novelmicrofluidic system. Chem Eng Technol, 2008, 31: 1223―1226 doi: 10.1002/ceat.200800027
Yeh C H, Zhao Q L, Lee S J, Lin Y C. Using aT-junction microfluidic chip for monodisperse calcium alginate microparticlesand encapsulation of nanoparticles. Sensorsand Actuators A, 2009, 151: 231―236 doi: 10.1016/j.sna.2009.02.036
Kashchiev D, Kaneko N, Sato K. Kinetics of crystallization in polydisperse emulsions. J Colloid Interface Sci, 1998, 208: 167―177 doi: 10.1006/jcis.1998.5760
Dombrowski R D, Litster J D, Wagner N J, He Y H. Crystallizationof alpha-lactose monohydrate in a drop-based microfluidic crystallizer. Chem Eng Sci, 2007, 62: 4802―4810 doi: 10.1016/j.ces.2007.05.033
Gong T, Shen J Y, Hu Z B, Marquez M, Cheng Z D. Nucleation rate measurementof colloidal crystallization using microfluidic emulsion droplets. Langmuir, 2007, 23: 2919―2923 doi: 10.1021/la063070d
Laval P, Lisai N, Salmon J B, Joanicot M. A microfluidic device based on droplet storage for screening solubilitydiagrams. Lab Chip, 2007, 7: 829―834 doi: 10.1039/b700799j
Laval P, Giroux C, Leng J. Microfluidic screening of potassium nitrate polymorphism. Journal of Crystal Growth, 2008, 310: 3121―3124 doi: 10.1016/j.jcrysgro.2008.03.009
Laval P, Salmon J B, Joanicot M. A microfluidic device for investigating crystal nucleationkinetics. Journal of Crystal Growth, 2007, 303: 622―628 doi: 10.1016/j.jcrysgro.2006.12.044
Laval P, Crombez A, Salmon J B. Microfluidic droplet method for nucleation kinetics measurements. Langmuir, 2009, 25: 1836―1841 doi: 10.1021/la802695r
Hansen C, Quake S R. Microfluidics in structuralbiology: smaller, faster, better. Currentopinion in structural biology, 2003, 13: 538―544 doi: 10.1016/j.sbi.2003.09.010
Zheng B, Gerdts C J, Ismagilov R F. Using nanoliter plugs in microfluidics to facilitateand understand protein crystallization. Current opinion in structural biology, 2005, 15: 548―555 doi: 10.1016/j.sbi.2005.08.009
Zheng B, Roach L S, Ismagilov R F. Screening of protein crystallization conditions on amicrofluidic chip using nanoliter-size droplets. J Am Chem Soc, 2003, 125: 11170―11171 doi: 10.1021/ja037166v
Zheng B, Tice J D, Roach L S, Ismagilov R F. A droplet-based, composite PDMS/glass capillary microfluidic systemfor evaluating protein crystallization conditions by microbatch andvapor-diffusion methods with on-chip X-ray diffraction. Angew Chem Int Ed, 2004, 43: 2508―2511 doi: 10.1002/anie.200453974
Zheng B, Tice J D, Ismagilov R F. Formation of arrayed droplets of soft lithography andtwo-phase fluid flow, and application in protein crystallization. Adv Mater, 2004, 16 (15): 1365―1368 doi: 10.1002/adma.200400590
Zheng B, Tice J D, Ismagilov R F. Formation of droplets of in microfluidic channels alternatingcomposition and applications to indexing of concentrations in droplet-basedassays. Anal Chem, 2004, 76, 4977―4982 doi: 10.1021/ac0495743
Zheng B, Ismagilov R F. A microfluidic approach forscreening submicroliter volumes against multiple reagents by usingpreformed arrays of nanoliter plugs in a three-phase liquid/liquid/gasflow. Angew Chem Int Ed Engl, 2005, 44: 2520―2523 doi: 10.1002/anie.200462857
Chen D L, Gerdts C J, Ismagilov R F. Using microfluidics to observe the effect of mixing onnucleation of protein crystals. J Am ChemSoc, 2005, 127: 9672―9673 doi: 10.1021/ja052279v
Chen D L, Li L, Reyes S, Adamson D N, Ismagilov R F. Using three-phase flow ofimmiscible liquids to prevent coalescence of droplets in microfluidicchannels: criteria to identify the third liquid and validation withprotein crystallization. Langmuir, 2007, 23: 2255―2260 doi: 10.1021/la062152z
