Microfluidic Mixing and the Formation of Nanoscale Lipid Vesicles
Andreas Jahn, Samuel M. Stavis, Jennifer S. Hong, Wyatt N. Vreeland, Don L. DeVoe, Michael Gaitan
We investigate the formation of unilamellar lipid vesicles (liposomes) with diameters of tens of nanometers by microfluidic hydrodynamic focusing (MHF). Our study includes liposome synthesis experiments and numerical modeling of our microfluidic implementation of the traditional alcohol injection method. We consider liposome formation with MHF from the perspective of fluid interfaces and not bulk fluid flow parameters, as we find that neither the hydrodynamically focused alcohol stream width nor the final alcohol concentration solely determines the vesicle formation process. Microfluidic device geometry in conjunction with hydrodynamic flow focusing strongly influences vesicle size distributions, providing a coarse method to control liposome size, while flow velocity provides a method to fine tune vesicle size in certain focusing regimes. Although liposome formation with MHF is relatively simple to implement experimentally, numerical simulations of the mixing process reveal a complex system of fluid flow and mass transfer, in addition to the lipid self-assembly process. Our results expand our fundamental understanding of the microfluidic environment that controls lipid self-assembly into liposomes and yield several technological advances for liposome synthesis.