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

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.

Surface acoustic wave devices for chemical sensing and microfluidics: a review and perspective

“…179 Along those lines, Westerhausen used a microchannel mixing strategy to synthesize mono-nucleic acid/lipid particles (mNALPs) by mixing separate liquid streams of lipids and nucleic acids in what amounted to a solvent exchange process. 180 …”

A microfluidic approach for sequential assembly of siRNA polyplexes with a defined structure-activity relationship

“…Automated production of pDNA PEI polyplexes in T-junctions has been shown by Kasper et al (2011) in our lab. Continuous or batch wise production of PEI pDNA polyplexes with active mixing by surface acoustic waves (SAWs) has been demonstrated by Westerhausen et al (2016) and Schnitzler et al (2019). The decrease in size and polydispersity is most impressive in lipid nanoparticle formulations with siRNA Krzysztoń et al, 2017).…”

“…Additionally, producing polyplexes without the help of organic solvents, which possibly alters the kinetically controlled assembly process, which needs mixing speeds in the order of 50 ms (Braun et al, 2005) to yield small particles, could facilitate the integration of this method into acetone intolerant applications. One solution could be the utilization of SAWs (Westerhausen et al, 2016) to avoid usage of organic solvents. In the end, there could be a small set of modules researchers could choose from according to the desired properties of their particles.…”

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