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Abstract
Ethanol injection and variations of it are a class of methods where two miscible phases---one
of which contains dissolved lipids---are mixed together leading to the self-assembly
of lipid molecules to form liposomes. This method has been suggested, among other
applications, for in-situ synthesis of liposomes as drug delivery capsules. However,
the mechanism that leads to a specific size selection of the liposomes in solution
based self-assembly in general, and in flow-focussing microfluidic devices in particular,
has so far not been established. Here we report two aspects of this problem. A simple
and easily fabricated device for synthesis of monodisperse unilamellar liposomes in
a co-axial flow-focussing microfluidic geometry is presented. We also show that the
size of liposomes is dependent on the extent of micro-convective mixing of the two
miscible phases. Here, a viscosity stratification induced hydrodynamic instability
leads to a gentle micro-mixing which results in larger liposome size than when the
streams are mixed turbulently. The results are in sharp contrast to a purely diffusive
mixing in macroscopic laminar flow that was believed to occur under these conditions.
Further precise quantification of the mixing characteristics should provide the insights
to develop a general theory for size selection for the class of ethanol injection
methods. This will also lay grounds for obtaining empirical evidence that will enable
better control of liposome sizes and for designing drug encapsulation and delivery
devices.