Many current technologies used in drug discovery and preclinical development programmes typically involve multi-step operations, extensive hands-on time, and lengthy liquid handling processes as well as low-throughput bioassays for functional validation and verification. We will discuss how microfluidic devices, with well-defined microchannel geometries and accurate flow control, can be used to generate uniform picolitre volume droplets (picodroplets) for use as miniaturized “test tubes” for high-throughput bioassays. 

Picodroplets can be used in a diverse range of applications. An important application of picodroplet microfluidics is single-cell analysis, in which single cells (and their corresponding secreted molecules) are encapsulated in a volume that is 100,000s of times lower than a typical-bulk volume method. This not only enables the rapid detection of secreted molecules and high-throughput sample processing but also time- and cost-effective screening compared to conventional assays.  More importantly, we have demonstrated that cells remain viable and functional in the picodroplets for several days, making the technology the ideal tool for a wide range of bioassays and research projects. 

Picodroplet-based technology can isolate and screen various types of cells, including bacteria, yeast, Chinese hamster ovary cells, HEK cells, primary B and T cells, and even stem cells. We will demonstrate how novel picodroplet bioassays can be used in a wide range of applications including biotherapeutic discovery, cell line development, cell therapy research and quality control, genome engineering (comprising CRISPR techniques) and synthetic biology.

Learning Objectives:

1. List the main categories of dispersed droplets, types of droplet generation, and manipulation of droplets.

2. Clarify the main advantages of droplet microfluidics.

3. Explain the workflow of an antigen-specific FRET assay in picodroplets for human plasma cells.