Assosiate Professor EPFL, The Swiss Federal Institute of Technology of Lausanne Lausanne, Vaud, Switzerland
Abstract: We have developed screening platforms enabling rapid identification of optimal drug cocktails for personalized cancer therapy1,2 . Results are available within 24h after surgery at consumables costs of less than 150 US$ per screen. The power of this platform has been demonstrated using cancer cell lines, xenograft mouse models and even human tumor biopsies. As a next step we are now translating the technology into a robust and easy to use diagnostic device, integrate transcriptomic readouts3 and start first-in-human studies. In parallel to this, we have developed fully integrated droplet-based microfluidic platforms for the screening of therapeutic antibodies4-6 . In these systems tiny aqueous droplets (picoliter volumes) surrounded by oil serve as independent assay vessels. The technology allows the direct screening of several hundred thousand primary, non-immortalized murine or even human B-cells for the secretion of antibodies that do not just bind to a drug target, but functionally inhibit it. Furthermore, we have established advanced single-cell antibody sequencing protocols enabling the screening of immune repertoires of COVID-19 infected patients for neutralizing antibodies. Taken together this should open the way for many new approaches in drug discovery, including personalized immunotherapy or the use of antibodies to control cellular pathways at will.
References 1 Eduati, F. et al. A microfluidics platform for combinatorial drug screening on cancer biopsies. Nature Communications 9, 1-13, doi:10.1038/s41467-018-04919-w (2018). 2 Utharala, R. et al. A microfluidic Braille valve platform for on-demand production, combinatorial screening and sorting of chemically distinct droplets. Nat Protoc 17, 2920-2965, doi:10.1038/s41596-022-00740-4 (2022). 3 Mathur, L. et al. Combi-seq for multiplexed transcriptome-based profiling of drug combinations using deterministic barcoding in single-cell droplets. Nat Commun 13, 4450, doi:10.1038/s41467-022-32197-0 (2022). 4 El Debs, B., Utharala, R., Balyasnikova, I. V., Griffiths, A. D. & Merten, C. A. Functional single-cell hybridoma screening using droplet-based microfluidics. Proc Natl Acad Sci U S A 109, 11570-11575, doi:10.1073/pnas.1204514109 (2012). 5 Shembekar, N., Hu, H., Eustace, D. & Merten, C. A. Single-Cell Droplet Microfluidic Screening for Antibodies Specifically Binding to Target Cells. Cell Rep 22, 2206-2215, doi:10.1016/j.celrep.2018.01.071 (2018). 6 Panwar, J., Autour, A. & Merten, C. A. Design and construction of a microfluidics workstation for high-throughput multi-wavelength fluorescence and transmittance activated droplet analysis and sorting. Nat Protoc 18, 1090-+, doi:10.1038/s41596-022-00796-2 (2023).
