Abstract

Using Microfluidics for Immune Cell Trafficking and Capture

Steven C. George, Professor, University of California, Davis

Microfluidic technology has played a leading role to advance our understanding of fundamental biological processes including cell separation and isolation, next generation sequencing, and cell trafficking.  Over the past five years our lab has applied the basic principles of microfluidics to control fluid shear and flow to create simple microphysiological systems to better understand:  1) how to capture and isolate rare immune cells from the peripheral circulation, and 2) the principles which guide and control immune cell (lymphocytes, monocytes, and neutrophils) trafficking in complex tissue microenvironments.  For the former, we leverage the ability to coat surfaces with antigens that are recognized by rare populations of B lymphocytes in the peripheral circulation.  We then control the shear force at the surface and can capture and isolate these rare cell populations.  Understanding how these rare cell populations evolve over time following viral (e.g., SARS-CoV-2, influenza) infection is central to understanding immunity following infection or immunization. For the latter, we are pursuing three projects.  The first involves neutrophil trafficking into the cardiac muscle during COVID19-induced “cytokine storm”, including counterstrategies that limit binding of neutrophils to the inflamed endothelium.  The second involves modeling myeloid cell-directed immunosuppression in the tumor microenvironment, and how counterstrategies such as inhibiting STAT3 signaling, can enhance CAR-T cell trafficking and effector function.  The third project describes small tumor cell-derived extracellular vesicle (sEV) transport (convection and binding to the extracellular matrix) and how the sEV can establish spatial gradients to guide monocyte migration in the tumor microenvironment.  This talk will provide an overview of our major results from each of these projects.