High-throughput nanoscale lipid vesicle synthesis in a semicircular contraction-expansion array microchannel

Towards potential applications in the field of nanomedicine, a new high-throughput synthesis method of lipid vesicles with tunable size as well as enhanced monodispersity is demonstrated using a semicircular contraction-expansion array (CEA) microchannel. Lipid vesicles are generated in the CEA microchannel by injecting lipids in isopropyl alcohol as a sample flow and phosphate buffered saline as a buffer flow, leading to spontaneous formation of lipid vesicles. In the CEA microchannel, Dean vortices cause three-dimensional (3D) lamination by continuously splitting and redirecting fluid streams, resulting in enhancement of fluid mixing. When considered only 3D laminating effect, it showed the best mixing efficiency in the range of flow rates of 12-15 mL/h. However, shear force effect also gives a strong influence on the formation of lipid vesicles, leading to the smallest size and uniform size distribution of lipid vesicles at a total flow rate of 18 mL/h. Consequently, from the interplay between high shear stress and 3D laminating effect, the lipid vesicles were generated with monodispersity and high throughput. The formation of lipid vesicles can be controlled with a total flow rate and a flow rate ratio between the sample and buffer fluids. The throughput of the lipid generation in the CEA microchannel was 10 times higher than previous works. In addition, the generated lipid vesicle populations were confirmed using a cryogenic transmission electron microscopy (cryo-TEM) technique.