Single-Cell BioMEMS Tools for Monitoring Cancer Immunotherapy: Nano Seminar Series

Seminar | March 15 | 2-3 p.m. | 4 LeConte Hall

 Prof. Rong Fan, Yale University, Biomedical Engineering

 Berkeley Nanosciences and Nanoengineering Institute

I will begin with discussing a novel bioMEMS device technology for single-cell immune function profiling, in particular, the co-detection of 40+ cytokines/chemokines at the level of single cells, representing the highest multiplexing recorded to date for a single-cell protein secretion assay.

I will describe how this microdevice called IsoCode was conceived, evolved over generations, further integrated with a fully automated single-cell processing platform called IsoLight comprising high-resolution optics, precision fluid handling and live cell incubation in the same system to truly enable robust and reproducible functional proteomics data at the single-cell level.

It has been widely used in immuno-oncology trial centers and pharmaceutical companies like Novartis, Kite Pharma (a Gilead Company), Bellicum, and many others to evaluate their cellular immunotherapy products. This microchip technology allowed for the full-spectrum dissection of T cell functions including genetically engineered chimeric antigen receptor T cells (CAR-T) in the treatment of patients with acute lymphoblastic leukemia or non-Hodgkin’s lymphoma.

Our data obtained from a medium-scale clinical trial with CD19 CAR-T cells demonstrated strong association between CAR-T cells’ polyfunctionality (the ability for a single T cell to co-produce multiple immune effector proteins) and patient response, which opens up new opportunities for predicting not only therapeutic efficacy but also potentially life-threatening immunotoxicity.

Recently, we further developed a standalone portable microchip for single-cell mRNA sequencing, which was combined with single-cell protein profiling to further elucidate the activation mechanisms of engineered T cells and facilitate the development of next-generation immunotherapies.

Rong Fan did his PhD in chemistry here at UC Berkeley (Go Bears!) and postdoc at CalTech, joining Yale in 2010. Awards include the NSF CAREER and the Packard Fellowship.