Abstract
Droplet-based single-cell sequencing has emerged as a very powerful tool to study the cellular heterogeneity in diseased tissues for a variety of biological problems. However, the current droplet generation with a single particle and cell encapsulation is a random process and suffers from a low yield that is unable to fulfill the high-throughput analysis requirement. In this work, we present a new fluorescence-activated droplet sorting (FADS) system that can isolate single-cell droplets at high accuracy and high yield using a highly focused surface acoustic wave (HFSAW) with a beam width around 50 mu m. The acoustic wave is locally coupled into the microfluidic channel for droplet sorting through a micropillar waveguide structure between the channel and the interdigitated transducer (IDT). This detachable acoustic sorting system allows the disposal of the microfluidic channel after a single use to avoid cross-contamination and keeps the expensive IDT device reusable. We have achieved rapid and accurate isolation of single-cell droplets with purity higher than 90% at similar to 1 kHz sorting rate with three different encapsulation contents. In addition, with the uniformly produced droplet size at similar to 40 mu m, the present acoustic FADS system enables effective sorting of small particles down to submicrometer size, which is challenging for existing fluorescence-activated cell sorting systems.