Single cell screening approaches for antibody discovery.

Microtools that have been developed to allow in depth interrogation of individual cells in high throughput are improving our understanding of biological processes at the single cell level and are opening up new possibilities for biological research. In relation to antibody discovery, these tools are now helping to maximise the full potential of well-established methodologies for antibody generation. Being complementary to both recombinant and native antibody secreting cells, some of these tools are finding widespread use in the field. In this review, we discuss how microtools for single cell analysis are addressing some of the limitations of traditional approaches for antibody screening. We describe the main classes of microtools for antibody discovery along with a comparison of each technology and an outlook for the future utility of some of these microtools for discovery and research.

Exploiting highly ordered subnanoliter volume microcapillaries as microtools for the analysis of antibody producing cells.

The interrogation of highly diverse repertoires of heterogeneous cell populations on a single cell basis increases the likelihood that a cell with unique characteristics will be identified. We have developed a new single cell analysis system comprising millions of bundled subnanoliter volume bioincubation chambers for the identification and recovery of target specific antibody secreting cells (ASCs). This platform integrates dual surface screening with dedicated user driven data analysis and automated cell recovery enabling multiple biophysical parameters to be tracked for millions of antibody leads in parallel. This direct clone analysis and selection technology is a clear deviation from current microfabricated well-based approaches and offers drastically enhanced screening throughput, simultaneous dual surface analysis, and rapid automated single cell recovery. The technology is also applicable to screening both bacterial and mammalian antibody secreting cells. We demonstrate the implementation and feasibility of this platform in identifying target specific antibodies from bacterial, hybridoma, and B cell libraries.