Microfluidic Fabrication of Giant Unilamellar Lipid Vesicles with Controlled Microdomain Formation

Abstract

Conventional methods for vesicle production lack the uniformity in size and composition required for many scientific and technological applications. To overcome these limitations, we present a microfluidic approach for the production of giant unilamellar vesicles (GUVs) using monodisperse water-in-oil-in-water (W/O/W) double emulsion drops as templates. The middle oil phase is a mixture of the lipids that ultimately form the GUV membranes, dissolved in a mixture of a highly-volatile good solvent and a less volatile poor solvent. The shell formed by the middle phase around the aqueous double emulsion core is less than a micron thick, much smaller than in typical double emulsion templates; this enables the fabrication of GUVs that contain minimal residual solvent within their membranes. The evaporation of the good solvent forces the bad solvent to dewet from the double emulsion drops, forming GUVs that stably encapsulate the material within their cores. By carefully controlling the lipid composition of the middle phase, we show that lipid microdomains form during the dewetting process. Our work thus demonstrates a straightforward approach to GUV fabrication that enables control over the GUV size, lipid composition, and the formation of microdomains within the GUV membrane.