Nanovial Manufacture via Liquid-Liquid Phase Separation

Microparticles — one to one hundred micrometer sized capsules — promise cheap and efficient analysis of cells and proteins. They already aid drug delivery, tissue engineering, and cell culturing and selection. Previous research has controlled microparticle shapes through polymerisation of aqueous two-phase systems (ATPS). But such approaches required sophisticated flow-focusing microfluidic devices, raising costs and restricting throughput. Recent work at the UCLA Di Carlo Lab uses thermally induced phase separation of a PEG-gelatin ATPS to form crescent or shell shapes after droplet creation, reducing complexity, improving parallelisation, and vastly reducing cost of microparticle manufacture.

To better predict how phase separation, surface tension, and buoyancy-induced flows control particle shapes, we propose a continuous Cahn-Hilliard-Stokes-Boussinesq (CHSB) model of thermally induced ATPS phase separation. The model captures correct minimal energy configurations, and shows how fluid flow and symmetry-breaking forces drive the system toward minimal energy crescents. The CHSB model further predicts that crescent formation can be greatly accelerated by shear induced recirculation for pressure driven channel flow. Models that neglect fluid dynamics do not achieve the correct minimal energy crescent shape after phase separation.