Abstract

High-throughput Physical Phenotyping of Cells for Biomedicine

Dino Di Carlo, Armond and Elena Hairapetian Chair in Engineering and Medicine, Professor and Vice Chair of Bioengineering, University of California Los Angeles

Drug development, diagnosis, and monitoring of diseases – from cancer to autoimmune disease - has had a strong focus on driving mutations and molecular changes underlying disease processes. In cancer, this approach has been extremely effective when a single driver mutation is responsible for the bulk of the resultant malignant behavior, e.g. in epidermal growth factor receptor (EGFR) mutations that constitutively activate cell growth and division in many non-small cell lung cancers. When targeting more complex behaviors – for example in cancer invasion or colonization, an understanding of molecular changes alone has not been sufficient to predict behavior. The ability to predict complex cell behavior from a small set of measureable molecular changes will likely remain limited to a few special cases for the foreseeable future. Biophysical measurements of cells can fill this gap. Physical measurements of cells integrate the variety of spatiotemporal changes in molecular species into a functional output that can be relevant to disease processes. Amongst the host of physical properties (the cellular physome) I will initially focus on the development of instruments that measure single-cell properties associated with metastasis and invasion, immune activation, and cell differentiation state. These include deformability, size, morphology, motility, adhesiveness, and contractility. This talk will introduce high-throughput and quantitative approaches addressing three of these areas – deformability cytometry, force phenotyping, and vortex trapping. I believe these new tools will enable new diagnostic and screening approaches that assay immune cell function, tumor cell malignancy, and many other cell fate decisions.