An Automated Single‐Cell Droplet‐Digital Microfluidic Platform for Monoclonal Antibody Discovery

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 20; no. 26; pp. e2308950 - n/a
• Main Authors: Ahmadi, Fatemeh, Tran, Hao, Letourneau, Natasha, Little, Samuel R., Fortin, Annie, Moraitis, Anna N., Shih, Steve C. C.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.06.2024
• Subjects: antibody discovery; deterministic co‐encapsulation; droplet operations; Droplets; droplet‐based microfluidics; Microfluidics; Monoclonal antibodies; Washing; deterministic co-encapsulation; droplet operations; droplet-based microfluidics; antibody discovery
• ISSN: 1613-6810; 1613-6829; 1613-6829
• DOI: 10.1002/smll.202308950

Monoclonal antibody (mAb) discovery plays a prominent role in diagnostic and therapeutic applications. Droplet microfluidics has become a standard technology for high‐throughput screening of antibody‐producing cells due to high droplet single‐cell confinement frequency and rapid analysis and sorting of the cells of interest with their secreted mAbs. In this work, a new method is described for on‐demand co‐encapsulation of cells that eliminates the difficulties associated with washing in between consecutive steps inside the droplets and enables the washing and addition of fresh media. The new platform identifies hybridoma cells that are expressing antibodies of interest using antibody‐characterization assays to find the best‐performing or rare‐cell antibody candidates. A new microfluidic method for antibody screening that allows for deterministic encapsulation of two cells and for frequent washes with minimal losses in the droplet. This new method is powered by droplet‐digital microfluidics, which combines droplet‐in‐flow techniques with digital microfluidic for the generation and the manipulation of droplets.