Expediting antibody discovery using Bioelectronica’s HypercellTM platform

Abstract

Antibody-based drugs have been successful in a range of therapeutic categories. However, generating monoclonal antibodies is time-consuming and expensive. A common approach is Hybridoma technology, which overcomes the short life-span of IgG-secreting plasma B cells in vitro. However, many plasma B cells are lost due to the low efficiency of hybridoma cell fusion (typically <10%).

Direct single B cell screening strategies have emerged to bypass hybridoma fusion and recombinatorial display, coupled with the generation of recombinant monoclonal antibodies through mammalian expression systems. Obtaining expression systems with the required productivity, specificity and stability for clinical or commercial use requires screening millions of cells and thousands of clones.

Bioelectronica’s HypercellTM platform is an emerging technology used throughout antibody discovery and cell-line development to identify and isolate single, high-antibody secreting cells from large pools (~10,000,000 cells) in short periods (ca. 48 hrs). This scalable “electrofluidic” sorting system reduces time and cost by integrating antigen-detection reagents and real-time computer vision analysis to expedite single cell sorting.

In this paper antigen-specific IgG-secreting hybridoma cells are identified and sorted by their secretion rate. The cells and reagents are encapsulated in a Polydisperse Oblate Dispersion system (PODs), incubated for 1–4 hours for signal gain, and loaded into the HypercellTM device for cell sorting. Alternatively, the mixture can be analyzed without sorting to produce single cell secretion “finger print” signatures that can help identify unique expression patterns and monitor cell line stability over culturing time.