Discovery of new antibodies for therapeutics requires discerning tools to identify rare cells producing specific antibodies among many similar ones. Bioprocess development also relies on methods to identify optimized cell lines producing heterologous proteins. This talk will describe an approach for integrated single-cell analysis that allows high-throughput screening (10^4–10^5 cells per screen) for novel antibodies and productive clones. The approach uses a modular collection of techniques employing microfabricated arrays of subnanoliter containers to enable flexible, reconfigurable processes that facilitate the discovery of novel antibodies and evaluation of clonal lines used in manufacturing heterologous proteins. The application of this nanowell-based technology to screening hybridomas and other antibody-secreting cells will be presented. The use of the same platform to identify high-producing strains for heterologous proteins will also be presented. How these measures on clonal lines can also provide insight into the biological factors that impede the recovery of stable production lines in such processes will also be discussed.
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