Recent progress in scale-up integration of microfluidic droplet generators

doi:10.11949/0438-1157.20210921

Abstract

Abstract:

Compared with conventional emulsification method, droplet microfluidics can controllably prepare monodisperse droplet templates in microchannels for synthesis of various functional microspheres, and is widely used in a lot of fields such as biological, medical, pharmaceutical and environmental engineering. Due to the low production rate of a single microfluidic droplet generator, scale-up integration of microfluidic droplet generators has become the technical difficulty to widespread utilization at the industrial scale. This paper reviews recent progress in scale-up integration of microfluidic droplet generators. Scale-up integration strategies for different types of microfluidic droplet generators, including droplet generators based on shear force, interfacial tension and passive break-up mechanisms, are mainly introduced.

Key words: microfluidics, microchannels, integration, scale-up, distribution network

摘要：

相比于传统乳化方法，液滴微流控技术可以在微通道内可控制备单分散液滴模板用于合成各种功能微球，被广泛应用于生物、医疗、制药、环境等领域。由于单个液滴制备微流控单元的产量低，液滴微流控的集成化放大成为了液滴微流控技术面向工业应用的技术难点。本文综述了近年来液滴微流控集成化放大方法的研究进展，重点介绍了不同类型液滴制备微流控单元集成化放大的研究进展，包括基于剪切力形成液滴、基于界面张力形成液滴和基于被动分裂形成液滴的液滴制备微流控单元的集成化放大方法。

关键词: 微流体学, 微通道, 集成, 放大, 分配网络

CLC Number:

TQ 050

Chuanfu DENG,Wei WANG,Rui XIE,Xiaojie JU,Zhuang LIU,Liangyin CHU. Recent progress in scale-up integration of microfluidic droplet generators[J]. CIESC Journal, 2021, 72(12): 5965-5974.

邓传富,汪伟,谢锐,巨晓洁,刘壮,褚良银. 液滴微流控的集成化放大方法研究进展[J]. 化工学报, 2021, 72(12): 5965-5974.

Figures/Tables 2

References 73

1	Utech S, Prodanovic R, Mao A S, et al. Microfluidic generation of monodisperse, structurally homogeneous alginate microgels for cell encapsulation and 3D cell culture[J]. Advanced Healthcare Materials, 2015, 4(11): 1628-1633.
2	Hou Y, Xie W Y, Achazi K, et al. Injectable degradable PVA microgels prepared by microfluidic technology for controlled osteogenic differentiation of mesenchymal stem cells[J]. Acta Biomaterialia, 2018, 77: 28-37.
3	Yu D, Dong Z Y, Lim H, et al. Microfluidic preparation, shrinkage, and surface modification of monodispersed alginate microbeads for 3D cell culture[J]. RSC Advances, 2019, 9(20): 11101-11110.
4	Wang Q, Qian K, Liu S, et al. X-ray visible and uniform alginate microspheres loaded with in situ synthesized BaSO₄ nanoparticles for in vivo transcatheter arterial embolization[J]. Biomacromolecules, 2015, 16(4): 1240-1246.
5	Beh C W, Fu Y L, Weiss C R, et al. Microfluidic-prepared, monodisperse, X-ray-visible, embolic microspheres for non-oncological embolization applications[J]. Lab on a Chip, 2020, 20(19): 3591-3600.
6	Han Y, Yang J L, Zhao W W, et al. Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis[J]. Bioactive Materials, 2021, 6(10): 3596-3607.
7	Zhao Z Y, Wang Z, Li G, et al. Injectable microfluidic hydrogel microspheres for cell and drug delivery[J]. Advanced Functional Materials, 2021, 31(31): 2103339.
8	Madrigal J L, Stilhano R S, Siltanen C, et al. Microfluidic generation of alginate microgels for the controlled delivery of lentivectors[J]. Journal of Materials Chemistry B, 2016, 4(43): 6989-6999.
9	Zhao X, Liu Y, Yu Y, et al. Hierarchically porous composite microparticles from microfluidics for controllable drug delivery[J]. Nanoscale, 2018, 10(26): 12595-12604.
10	He F, Zhang M J, Wang W, et al. Designable polymeric microparticles from droplet microfluidics for controlled drug release[J]. Advanced Materials Technologies, 2019, 4(6): 1800687.
11	Caballero Aguilar L M, Duchi S, Onofrillo C, et al. Formation of alginate microspheres prepared by optimized microfluidics parameters for high encapsulation of bioactive molecules[J]. Journal of Colloid and Interface Science, 2021, 587: 240-251.
12	Wang J M, Wang X Y, Zhu P G, et al. Microfluidic rapid fabrication of tunable polyvinyl alcohol microspheres for adsorption applications[J]. Materials, 2019, 12(22): 3712.
13	Chen L, Zhang M J, Zhang S Y, et al. Simple and continuous fabrication of self-propelled micromotors with photocatalytic metal-organic frameworks for enhanced synergistic environmental remediation[J]. ACS Applied Materials & Interfaces, 2020, 12(31): 35120-35131.
14	Liu J R, Chen H, Shi X J, et al. Hydrogel microcapsules with photocatalytic nanoparticles for removal of organic pollutants[J]. Environmental Science: Nano, 2020, 7(2): 656-664.
15	Zhang M J, Chen T, Zhang P, et al. Magnetic hierarchical porous SiO₂ microparticles from droplet microfluidics for water decontamination[J]. Soft Matter, 2020, 16(10): 2581-2593.
16	Liu W Y, Ju X J, Pu X Q, et al. Functional capsules encapsulating molecular-recognizable nanogels for facile removal of organic micro-pollutants from water[J]. Engineering, 2021, 7(5): 636-646.
17	Jeong H H, Issadore D, Lee D. Recent developments in scale-up of microfluidic emulsion generation via parallelization[J]. Korean Journal of Chemical Engineering, 2016, 33(6): 1757-1766.
18	Holtze C. Large-scale droplet production in microfluidic devices-an industrial perspective[J]. Journal of Physics D: Applied Physics, 2013, 46(11): 114008.
19	Schroën K, Bliznyuk O, Muijlwijk K, et al. Microfluidic emulsification devices: from micrometer insights to large-scale food emulsion production[J]. Current Opinion in Food Science, 2015, 3: 33-40.
20	Shen Q Y, Zhang C, Tahir M F, et al. Numbering-up strategies of micro-chemical process: uniformity of distribution of multiphase flow in parallel microchannels[J]. Chemical Engineering and Processing-Process Intensification, 2018, 132: 148-159.
21	Nisisako T. Recent advances in microfluidic production of Janus droplets and particles[J]. Current Opinion in Colloid & Interface Science, 2016, 25: 1-12.
22	Thorsen T, Roberts R W, Arnold F H, et al. Dynamic pattern formation in a vesicle-generating microfluidic device[J]. Physical Review Letters, 2001, 86(18): 4163-4166.
23	Utada A S, Fernandez-Nieves A, Stone H A, et al. Dripping to jetting transitions in coflowing liquid streams[J]. Physical Review Letters, 2007, 99(9): 094502.
24	Fu T T, Wu Y N, Ma Y G, et al. Droplet formation and breakup dynamics in microfluidic flow-focusing devices: from dripping to jetting[J]. Chemical Engineering Science, 2012, 84: 207-217.
25	Amstad E, Chen X M, Eggersdorfer M, et al. Parallelization of microfluidic flow-focusing devices[J]. Physical Review E, 2017, 95(4): 043105.
26	Zhu P G, Wang L Q. Passive and active droplet generation with microfluidics: a review[J]. Lab on a Chip, 2017, 17(1): 34-75.
27	Utada A S, Chu L Y, Fernandez-Nieves A, et al. Dripping, jetting, drops, and wetting: the magic of microfluidics[J]. MRS Bulletin, 2007, 32(9): 702-708.
28	Jeong H H, Yelleswarapu V R, Yadavali S, et al. Kilo-scale droplet generation in three-dimensional monolithic elastomer device (3D MED)[J]. Lab on a Chip, 2015, 15(23): 4387-4392.
29	Muluneh M, Issadore D. Hybrid soft-lithography/laser machined microchips for the parallel generation of droplets[J]. Lab on a Chip, 2013, 13(24): 4750-4754.
30	Jeong H H, Yadavali S, Issadore D, et al. Liter-scale production of uniform gas bubbles via parallelization of flow-focusing generators[J]. Lab on a Chip, 2017, 17(15): 2667-2673.
31	Romanowsky M B, Abate A R, Rotem A, et al. High throughput production of single core double emulsions in a parallelized microfluidic device[J]. Lab on a Chip, 2012, 12(4): 802.
32	Yadavali S, Jeong H H, Lee D, et al. Silicon and glass very large scale microfluidic droplet integration for terascale generation of polymer microparticles[J]. Nature Communications, 2018, 9: 1222.
33	Femmer T, Jans A, Eswein R, et al. High-throughput generation of emulsions and microgels in parallelized microfluidic drop-makers prepared by rapid prototyping[J]. ACS Applied Materials & Interfaces, 2015, 7(23): 12635-12638.
34	Han T T, Zhang L, Xu H, et al. Factory-on-chip: modularised microfluidic reactors for continuous mass production of functional materials[J]. Chemical Engineering Journal, 2017, 326: 765-773.
35	Huang Y C, Han T T, Xuan J, et al. Design criteria and applications of multi-channel parallel microfluidic module[J]. Journal of Micromechanics and Microengineering, 2018, 28(10): 105021.
36	Cui Y J, Li Y K, Wang K, et al. High-throughput preparation of uniform tiny droplets in multiple capillaries embedded stepwise microchannels[J]. Journal of Flow Chemistry, 2020, 10(1): 271-282.
37	Conchouso D, Castro D, Khan S A, et al. Three-dimensional parallelization of microfluidic droplet generators for a litre per hour volume production of single emulsions[J]. Lab on a Chip, 2014, 14(16): 3011.
38	Li W, Greener J, Voicu D, et al. Multiple modular microfluidic (M3) reactors for the synthesis of polymer particles[J]. Lab on a Chip, 2009, 9(18): 2715.
39	Bardin D, Kendall M R, Dayton P A, et al. Parallel generation of uniform fine droplets at hundreds of kilohertz in a flow-focusing module[J]. Biomicrofluidics, 2013, 7(3): 034112.
40	Nisisako T, Torii T. Microfluidic large-scale integration on a chip for mass production of monodisperse droplets and particles[J]. Lab DN a Chip, 2008, 8(2): 287-293.
41	Nisisako T, Ando T, Hatsuzawa T. High-volume production of single and compound emulsions in a microfluidic parallelization arrangement coupled with coaxial annular world-to-chip interfaces[J]. Lab on a Chip, 2012, 12(18): 3426-3435.
42	Gelin P, Bihi I, Ziemecka I, et al. Microfluidic device for high-throughput production of monodisperse droplets[J]. Industrial & Engineering Chemistry Research, 2020, 59(28): 12784-12791.
43	Tetradis-Meris G, Rossetti D, Pulido de Torres C, et al. Novel parallel integration of microfluidic device network for emulsion formation[J]. Industrial & Engineering Chemistry Research, 2009, 48(19): 8881-8889.
44	Kawakatsu T, Trägårdh G, Trägårdh C, et al. The effect of the hydrophobicity of microchannels and components in water and oil phases on droplet formation in microchannel water-in-oil emulsification[J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2001, 179(1): 29-37.
45	Dangla R, Kayi S C, Baroud C N. Droplet microfluidics driven by gradients of confinement[J]. PNAS, 2013, 110(3): 853-858.
46	Eggersdorfer M L, Seybold H, Ofner A, et al. Wetting controls of droplet formation in step emulsification[J]. PNAS, 2018, 115(38): 9479-9484.
47	Liu Z W, Duan C, Jiang S K, et al. Microfluidic step emulsification techniques based on spontaneous transformation mechanism: a review[J]. Journal of Industrial and Engineering Chemistry, 2020, 92: 18-40.
48	Shi Z, Lai X, Sun C, et al. Step emulsification in microfluidic droplet generation: mechanisms and structures[J]. Chemical Communications, 2020, 56(64): 9056-9066.
49	Amstad E, Chemama M, Eggersdorfer M, et al. Robust scalable high throughput production of monodisperse drops[J]. Lab on a Chip, 2016, 16(21): 4163-4172.
50	Håti A G, Szymborski T R, Steinacher M, et al. Production of monodisperse drops from viscous fluids[J]. Lab on a Chip, 2018, 18(4): 648-654.
51	Teston E, Hingot V, Faugeras V, et al. A versatile and robust microfluidic device for capillary-sized simple or multiple emulsions production[J]. Biomedical Microdevices, 2018, 20(4): 1-12.
52	de Rutte J M, Koh J, Di Carlo D. Scalable high-throughput production of modular microgels for in situ assembly of microporous tissue scaffolds[J]. Advanced Functional Materials, 2019, 29(25): 1900071.
53	Zoratto N, Di Lisa D, de Rutte J, et al. In situ forming microporous gelatin methacryloyl hydrogel scaffolds from thermostable microgels for tissue engineering[J]. Bioengineering & Translational Medicine, 2020, 5(3): e10180.
54	Sugiura S, Nakajima M, Tong J H, et al. Preparation of monodispersed solid lipid microspheres using a microchannel emulsification technique[J]. Journal of Colloid and Interface Science, 2000, 227(1): 95-103.
55	Kobayashi I, Takano T, Maeda R, et al. Straight-through microchannel devices for generating monodisperse emulsion droplets several microns in size[J]. Microfluidics and Nanofluidics, 2008, 4(3): 167-177.
56	van Dijke K, Veldhuis G, Schroën K, et al. Parallelized edge-based droplet generation (EDGE) devices[J]. Lab on a Chip, 2009, 9(19): 2824-2830.
57	Sahin S, Schroën K. Partitioned EDGE devices for high throughput production of monodisperse emulsion droplets with two distinct sizes[J]. Lab on a Chip, 2015, 15(11): 2486-2495.
58	Chung C H Y, Cui B B, Song R Y, et al. Scalable production of monodisperse functional microspheres by multilayer parallelization of high aspect ratio microfluidic channels[J]. Micromachines, 2019, 10(9): 592.
59	Eberhardt A, Bošković D, Loebbecke S, et al. Customized design of scalable microfluidic droplet generators using step-emulsification methods[J]. Chemical Engineering & Technology, 2019, 42(10): 2195-2201.
60	ten Klooster S, Sahin S, Schroën K. Monodisperse droplet formation by spontaneous and interaction based mechanisms in partitioned EDGE microfluidic device[J]. Scientific Reports, 2019, 9: 7820.
61	Eggersdorfer M L, Zheng W, Nawar S, et al. Tandem emulsification for high-throughput production of double emulsions[J]. Lab on a Chip, 2017, 17(5): 936-942.
62	Ofner A, Mattich I, Hagander M, et al. Controlled massive encapsulation via tandem step emulsification in glass[J]. Advanced Functional Materials, 2019, 29(4): 1806821.
63	Kobayashi I, Wada Y, Uemura K, et al. Microchannel emulsification for mass production of uniform fine droplets: integration of microchannel arrays on a chip[J]. Microfluidics and Nanofluidics, 2010, 8(2): 255-262.
64	Ofner A, Moore D G, Rühs P A, et al. High-throughput step emulsification for the production of functional materials using a glass microfluidic device[J]. Macromolecular Chemistry and Physics, 2017, 218(2): 1600472.
65	Vladisavljević G T, Ekanem E E, Zhang Z L, et al. Long-term stability of droplet production by microchannel (step) emulsification in microfluidic silicon chips with large number of terraced microchannels[J]. Chemical Engineering Journal, 2018, 333: 380-391.
66	Stolovicki E, Ziblat R, Weitz D A. Throughput enhancement of parallel step emulsifier devices by shear-free and efficient nozzle clearance[J]. Lab on a Chip, 2018, 18(1): 132-138.
67	Leshansky A M, Pismen L M. Breakup of drops in a microfluidic T junction[J]. Physics of Fluids, 2009, 21(2): 023303.
68	Link D R, Anna S L, Weitz D A, et al. Geometrically mediated breakup of drops in microfluidic devices[J]. Physical Review Letters, 2004, 92(5): 054503.
69	Adamson D N, Mustafi D, Zhang J X, et al. Production of arrays of chemically distinct nanolitre plugs via repeated splitting in microfluidic devices[J]. Lab on a Chip, 2006, 6(9): 1178-1186.
70	Vladisavljević G T, Khalid N, Neves M A, et al. Industrial lab-on-a-chip: design, applications and scale-up for drug discovery and delivery[J]. Advanced Drug Delivery Reviews, 2013, 65(11/12): 1626-1663.
71	Abate A R, Weitz D A. Faster multiple emulsification with drop splitting[J]. Lab on a Chip, 2011, 11(11): 1911.
72	Hoang D A, Haringa C, Portela L M, et al. Design and characterization of bubble-splitting distributor for scaled-out multiphase microreactors[J]. Chemical Engineering Journal, 2014, 236: 545-554.
73	Kim C M, Kim G M. Fabrication of 512-channel geometrical passive breakup device for high-throughput microdroplet production[J]. Micromachines, 2019, 10(10): 709.

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