A Tunable Microfluidic Device to Investigate the Influence of Fluid-Dynamics on Polymer Nanoprecipitation

Abstract

Polymer drug-embedding nanocapsules are attracting increasing attention as effective tools for the targeted delivery of pharmaceutical molecules on specific biological tissues. Besides, it is well established that an effective selectivity of the delivery dictates that the size of the carrier particles be accurately controlled, thus maintaining the size dispersion of the particle population as low as possible. To this end, microfluidics-assisted precipitation provides a promising alternative to the traditional processes in that the structure of the flow - ultimately controlling the particle size distribution - can be reliably predicted from the solution of Navier-Stokes equations in the laminar regime. Notwithstanding the great potential provided by microfluidics techniques, much about the interaction between fluid-dynamics and polymer transport and precipitation is yet to be understood. In this work, we investigate polymer precipitation in a simple cross-junction inflow-outflow microchannel, which has proven a viable benchmark to gain insight into the physics of nanoprecipitation in that the particle size distribution is sensitively dependent on the flow operating conditions. Specifically, previous experimental work by some of these authors proved that average particle size can vary by an order of magnitude for operating conditions where the solvent flow rate varies by a factor of three, while keeping the non-solvent flow rate constant. The scope of this work is to show that such sensitive dependence on operating conditions finds direct correspondence in the kinematic structure of the flow, which undergoes abrupt qualitative changes in the same range of operating conditions, provided a fully three-dimensional solution of the incompressible Navier-Stokes equation (thus retaining the inertial term in momentum balance) is afforded.