High-throughput Synthesis of Multi-functional Nanoscale Lipid Vesicles in a Contraction??Expansion Array Microchannel

Abstract

This paper reports a simple method of encapsulating materials inside of lipid vesicles, along with tunable size and enhanced polydispersity of the size distribution. We fabricated a contraction??expansion array (CEA) microchannel in the shape of semicircular groove arrays by using poly(dimethylsiloxane) molding technique. The device has the 50 ??m deep microchannel containing a uniform array of contraction??expansion microchannel. The channel has a width of 350 ??m and 50 ??m on the expansion and contraction region, respectively. The interval between each region is 600 ??m. The entire mixing channel consists of 30 array units. Lipid vesicles were generated in the CEA microchannel by injecting lipids??dimyristoylphosphatidylcholine and cholesterol in a molar ratio of 1:1??in isopropyl alcohol as a sample flow and phosphate buffered saline (PBS) as a buffer flow, leading to spontaneous formation of liposomes. In the CEA microchannel, the fluid experiences Dean vortices at high Re (> 5), passing through the contraction regions. The injected lipids are rapidly mixed with PBS by three-dimensional (3D) laminating effect attributed from the Dean vortices. In such a CEA microchannel, Dean vortices lead to 3D lamination effected by continuously splitting and redirecting fluid streams, resulting in enhancement of fluid mixing. In addition, the injected lipids and PBS experience high shear stress relative to reducing size distribution of lipid vesicles throughout the CEA microchannel. From the interplay between high shear stress and 3D laminating effect, the lipid vesicles are generated with monodispersity and high throughput. Consequently, the formation of lipid vesicles can be controlled with a total flow rate and a flow rate ratio between the sample and buffer fluids. Generated lipid vesicles from the CEA microchannel showed narrower size distribution than ones from the linear microchannel at a flow rate of 18 mL/h (Re = ~25). The throughput of the lipid generation in...