Controllable Acoustic Mixing of Fluids in Microchannels for the Fabrication of Therapeutic Nanoparticles

Micromachines (Basel). 2016 Sep 2;7(9):150. doi: 10.3390/mi7090150.

Abstract

Fifteen years ago, surface acoustic waves (SAW) were found to be able to drive fluids and numerous applications in microfluidics have been developed since. Here, we review the progress made and report on new approaches in setting-up microfluidic, continuous flow acoustic mixing. In a microchannel, chaotic advection is achieved by generation of a SAW driven fluid jet perpendicular to the mean flow direction. Using a high speed video camera and particle image velocimetry, we measure the flow velocities and show that mixing is achieved in a particularly controllable and fast way. The mixing quality is determined as a function of system parameters: SAW power, volume flux and fluid viscosity. Exploring the parameter space of mixing provides a practical guide for acoustic mixing in microchannels and allows for adopting conditions to different solvents, as e.g., required for the generation of nanoscale particles from alcoholic phases. We exemplarily demonstrate the potential of SAW based continuous flow mixing for the production of therapeutic nucleic acid nanoparticles assembled from polymer and lipid solutions.

Keywords: acoustic streaming; lab-on-a-chip; lipoplexes; microfluidic mixing; mono-nucleic acid/lipid particles (mNALPs); plasmid DNA (pDNA); polyethylenimine (PEI); polyplexes; siRNA; surface acoustic waves; therapeutic nanoparticles.