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 nanoliter 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 microL 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.