Microfluidic Generation of Lipidic Mesophases for Membrane Protein Crystallization

We report on a microfluidic method for the formation of aqueous/lipid mesophases to enable screening of suitable crystallization conditions of membrane proteins from a membrane-like phase in sub-20 nL volumes. This integrated microfluidic chip and the employed mixing strategy address the specific challenges associated with the mixing of fluids of highly different viscosities (here a factor of 30) as well as the non-Newtonian character of the resulting mesophases. The chip requires less than 20 nL of material per condition screened, whereas typically on the order of 10 mu L or more is needed for a batch preparation in the present screening methods. We validated our approach with the successful crystallization of the membrane protein bacteriorhodopsin.