Versatile hybrid acoustic micromixer with demonstration of circulating cell-free DNA extraction from sub-ml plasma samples

Abstract

Acoustic micromixers have attracted considerable attention in the last years since they can deliver high mixing efficiencies without the need for movable components. However, their adoption in the academic and industrial microfluidics community has been limited, possibly due to the reduced flexibility and accessibility of previous designs since most of them are application-specific and fabricated with techniques that are expensive, not widely available and difficult to integrate with other manufacturing technologies. In this work, we describe a simple, yet highly versatile, bubble-based micromixer module fabricated with a combination of low-cost rapid prototyping techniques. The hybrid approach enables the integration of the module into practically any substrate and the individual control of multiple micromixers embedded within the same monolithic chip. The module can operate under static and continuous flow conditions showing enhanced mixing capabilities compared to similar devices. We show that the system is capable of performing cell-free DNA extractions from small volumes of blood plasma (≤500 μl) with up to a ten-fold increase in capture efficiency when compared to control methods.