Lab on a Particle: Democratizing Single-Cell Secretion Assays

Techniques to analyze and sort single cells based on secreted products have the potential to transform our understanding of cellular biology as well as accelerate the development of next generation cell and antibody therapies. However, secretions are rapidly transported away from cells, such that specialized equipment and expertise has been required to compartmentalize cells and capture their secretions. In this presentation I will explain how cavity-containing hydrogel microparticles can be leveraged to perform functional single-cell secretion analysis and sorting in high-throughput using only commonly accessible lab infrastructure. These microparticles act as a solid support which facilitates cell attachment, templates formation of uniform sub-nanoliter aqueous compartments which prevent cross-talk between cells, and captures secreted proteins. Using this “lab on a particle” platform, we demonstrate high-throughput analysis and sorting of Chinese Hamster Ovary cells based on their relative production of human IgG using commercially available flow sorters. We successfully screen over 100,000 cells in a single day and isolate a subpopulation of cells from a production grade cell line that maintained ~50% increased levels of antibody production after 2 weeks of culture. Microparticles can be fabricated in bulk and are easily distributed and used, democratizing access to high-throughput functional cell screening. Ultimately, we believe the ability to rapidly create millions of uniform compartments using lab on a particle technology can extend across fields, providing a fundamental tool that can enable any researcher to perform single-cell and single-molecule assays in the future.

Learning Objectives:

1. Define current approaches to single-cell secretion analysis and identify limitations

2. Explain how microparticles can be leveraged to perform assays with standard lab equipment