Oil-Free Acoustofluidic Droplet Generation for Multicellular Tumor Spheroid Culture

ACS Appl Bio Mater. 2019 Sep 16;2(9):4097-4105. doi: 10.1021/acsabm.9b00617. Epub 2019 Aug 22.

Abstract

We present an easy-to-assemble microfluidic system for synthesizing cell-loaded dextran/alginate (DEX/ALG) hydrogel spheres using an aqueous two-phase system (ATPS) for templated fabrication of multicellular tumor spheroids (MTSs). An audio speaker driven by an amplified output of a waveform generator or smartphone provides acoustic modulation to drive the breakup of an ATPS into MTS template droplets within microcapillary fluidic devices. We apply extensions of Plateau-Rayleigh theory to help define the flow and frequency parameter space necessary for acoustofluidic ATPS droplet formation in these devices. This method provides a simple droplet microfluidic approach using off-the-shelf acoustic components for quickly initiating MTSs and subsequent 3D cell culture.

Keywords: ATPS; acoustics; cancer; capillary; hydrogels; microfluidics; spheroid.