Microfluidic production of liposomes through liquid--liquid phase separation in ternary droplets
Xu-Chun Song, Zi-Han Zhou, Ya-Lan Yu, Nan-Nan Deng
Microfluidic production of liposomes through liquid--liquid phase separation in ternary droplets
Liposomes, the self-assembled phospholipid vesicles, have been extensively used in various fields such as artificial cells, drug delivery systems, biosensors and cosmetics. However, current microfluidic routes to liposomes mostly rely on water-in-oil-in-water double emulsion droplets as templates, and require complex fabrication of microfluidic devices, and tedious manipulation of multiphase fluids. Here we present a simple microfluidic approach to preparing monodisperse liposomes from oil-in-water droplets. For demonstration, we used butyl acetate-water-ethanol ternary mixtures as inner phase and an aqueous solution of surfactants as outer phase to make oil-in-water droplets, which can evolve into water-in-oil-in-water double emulsion droplets by liquid–liquid phase separation of ternary mixtures. Subsequently, the resultant water-in-oil-in-water droplets underwent a dewetting transition to form separated monodisperse liposomes and residual oil droplets, with the assistance of surfactants. The method is simple, does not require complex microfluidic devices and tedious manipulation, and provides a new platform for controllable preparation of liposomes.
microfluidics / liposomes / ternary droplets / phase separation
[1] |
Podolsky K A, Devaraj N K. Synthesis of lipid membranes for artificial cells. Nature Reviews. Chemistry, 2021, 5(10): 676–694
CrossRef
Google scholar
|
[2] |
Pattni B S, Chupin V V, Torchilin V P. New developments in liposomal drug delivery. Chemical Reviews, 2015, 115(19): 10938–10966
CrossRef
Google scholar
|
[3] |
Torchilin V P. Recent advances with liposomes as pharmaceutical carriers. Nature Reviews. Drug Discovery, 2005, 4(2): 145–160
CrossRef
Google scholar
|
[4] |
Mansy S S, Schrum J P, Krishnamurthy M, Tobe S, Treco D A, Szostak J W. Template-directed synthesis of a genetic polymer in a model protocell. Nature, 2008, 454(7200): 122–125
CrossRef
Google scholar
|
[5] |
Bolinger P Y, Stamou D, Vogel H. Integrated nanoreactor systems: triggering the release and mixing of compounds inside single vesicles. Journal of the American Chemical Society, 2004, 126(28): 8594–8595
CrossRef
Google scholar
|
[6] |
Noireaux V, Libchaber A. A vesicle bioreactor as a step toward an artificial cell assembly. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101(51): 17669–17674
CrossRef
Google scholar
|
[7] |
Villarreal F, Tan C. Cell-free systems in the new age of synthetic biology. Frontiers of Chemical Science and Engineering, 2017, 11(1): 58–65
CrossRef
Google scholar
|
[8] |
Bally M, Bailey K, Sugihara K, Grieshaber D, Voros J, Stadler B. Liposome and lipid bilayer arrays towards biosensing applications. Small, 2010, 6(22): 2481–2497
CrossRef
Google scholar
|
[9] |
Zhou J, Wang Q X, Zhang C Y. Liposome-quantum dot complexes enable multiplexed detection of attomolar DNAs without target amplification. Journal of the American Chemical Society, 2013, 135(6): 2056–2059
CrossRef
Google scholar
|
[10] |
Horger K S, Estes D J, Capone R, Mayer M. Films of agarose enable rapid formation of giant liposomes in solutions of physiologic ionic strength. Journal of the American Chemical Society, 2009, 131(5): 1810–1819
CrossRef
Google scholar
|
[11] |
Pereno V, Carugo D, Bau L, Sezgin E, Bernardino de la Serna J, Eggeling C, Stride E. Electroformation of giant unilamellar vesicles on stainless steel electrodes. ACS Omega, 2017, 2(3): 994–1002
CrossRef
Google scholar
|
[12] |
Bi H, Yang B, Wang L, Cao W, Han X. Electroformation of giant unilamellar vesicles using interdigitated ITO electrodes. Journal of Materials Chemistry. A, Materials for Energy and Sustainability, 2013, 1(24): 7125–7130
CrossRef
Google scholar
|
[13] |
Pautot S, Frisken B J, Weitz D A. Engineering asymmetric vesicles. Proceedings of the National Academy of Sciences of the United States of America, 2003, 100(19): 10718–10721
CrossRef
Google scholar
|
[14] |
Rodriguez N, Pincet F, Cribier S. Giant vesicles formed by gentle hydration and electroformation: a comparison by fluorescence microscopy. Colloids and Surfaces. B, Biointerfaces, 2005, 42(2): 125–130
CrossRef
Google scholar
|
[15] |
Runas K A, Malmstadt N. Low levels of lipid oxidation radically increase the passive permeability of lipid bilayers. Soft Matter, 2015, 11(3): 499–505
CrossRef
Google scholar
|
[16] |
Pautot S, Frisken B J, Weitz D A. Production of unilamellar vesicles using an inverted emulsion. Langmuir, 2003, 19(7): 2870–2879
CrossRef
Google scholar
|
[17] |
Yu Y L, Zhou Z H, Yu W T, Song Y Z, Xie M Q. Preparation of magnetic porous microspheres and their ability to remove oils. Macromolecular Materials and Engineering, 2020, 305(1): 1900452
CrossRef
Google scholar
|
[18] |
Liu Y, Li Y, Hensel A, Brandner J J, Zhang K, Du X, Yang Y. A review on emulsification via microfluidic processes. Frontiers of Chemical Science and Engineering, 2020, 14(3): 350–364
CrossRef
Google scholar
|
[19] |
Wang W, Zhang M J, Chu L Y. Functional polymeric microparticles engineered from controllable microfluidic emulsions. Accounts of Chemical Research, 2014, 47(2): 373–384
CrossRef
Google scholar
|
[20] |
Wang W, Xie R, Ju X J, Luo T, Liu L, Weitz D A, Chu L Y. Controllable microfluidic production of multicomponent multiple emulsions. Lab on a Chip, 2011, 11(9): 1587–1592
CrossRef
Google scholar
|
[21] |
Geng Y, Ling S, Huang J, Xu J. Multiphase microfluidics: fundamentals, fabrication, and functions. Small, 2020, 16(6): 1906357
CrossRef
Google scholar
|
[22] |
Arriaga L R, Datta S S, Kim S H, Amstad E, Kodger T E, Monroy F, Weitz D A. Ultrathin shell double emulsion templated giant unilamellar lipid vesicles with controlled microdomain formation. Small, 2014, 10(5): 950–956
CrossRef
Google scholar
|
[23] |
Deshpande S, Caspi Y, Meijering A E C, Dekker C. Octanol-assisted liposome assembly on chip. Nature Communications, 2016, 7(1): 10447
CrossRef
Google scholar
|
[24] |
Deng N N, Yelleswarapu M, Huck W T. Monodisperse uni- and multicompartment liposomes. Journal of the American Chemical Society, 2016, 138(24): 7584–7591
CrossRef
Google scholar
|
[25] |
Deng N N, Yelleswarapu M, Zheng L, Huck W T S. Microfluidic assembly of monodisperse vesosomes as artificial cell models. Journal of the American Chemical Society, 2017, 139(2): 587–590
CrossRef
Google scholar
|
[26] |
Choi C H, Weitz D A, Lee C S. One step formation of controllable complex emulsions: from functional particles to simultaneous encapsulation of hydrophilic and hydrophobic agents into desired position. Advanced Materials, 2013, 25(18): 2536–2541
CrossRef
Google scholar
|
[27] |
Song Y, Sauret A, Shum H C. All-aqueous multiphase microfluidics. Biomicrofluidics, 2013, 7(6): 061301
CrossRef
Google scholar
|
[28] |
Haase M F, Brujic J. Tailoring of high-order multiple emulsions by the liquid-liquid phase separation of ternary mixtures. Angewandte Chemie International Edition, 2014, 53(44): 11793–11797
CrossRef
Google scholar
|
[29] |
Deng N N, Vibhute M A, Zheng L, Zhao H, Yelleswarapu M, Huck W T S. Macromolecularly crowded protocells from reversibly shrinking monodisperse liposomes. Journal of the American Chemical Society, 2018, 140(24): 7399–7402
CrossRef
Google scholar
|
/
〈 | 〉 |