A single droplet dispensing system for high-throughput screening and reliable recovery of rare events.

Abstract

Microfluidic droplet sorting has emerged as a powerful technique for a broad spectrum of biomedical applications ranging from single cell analysis to high-throughput drug screening, biomarker detection and tissue engineering. However, the controlled and reliable retrieval of selected droplets for further off-chip analysis and processing is a significant challenge in droplet sorting, particularly in high-throughput applications with low expected hit rates. In this study, we present a microfluidic platform capable of sorting and dispensing individual droplets with minimal loss rates. We demonstrate our direct transfer mechanism by placing selected droplets containing hybridoma cells into microwells, eliminating the need for manual and often lossy handling steps. Sorted droplets are dispensed <i>via</i> a novel 3D-printed dispensing nozzle, enabling precise and controlled placement of selected single droplets into individual wells without affecting the microfluidic sorting flow. The sorting and transfer process is monitored in real time, which provides feedback and quality control of the entire workflow. Our integrated microfluidic system holds great potential for applications requiring high-throughput droplet sorting with minimal sample loss and precise dispensing into microwells, such as screening for therapeutical antibodies or monoclonal cells.