Wilbur Lam, M.D., Ph.D. (Georgia Institute of Technology & Emory University)
Brandon Dixon, Ph.D. (Georgia Institute of Technology)
Todd Sulchek, Ph.D. (Georgia Institute of Technology)
Susan Thomas, Ph.D. (Georgia Institute of Technology)
Hua Wang, Ph.D. (Georgia Institute of Technology)
DEVELOPING MICROFLUIDIC SYSTEMS TO DECOUPLE BIOPHYSICAL AND BIOCHEMICAL ASPECTS OF HEMATOLOGICAL PROCESSES
Recent research has revealed that cells dynamically sense and respond to their physical microenvironments. For instance, in hematology specifically, it was shown that shear mediated red blood cell (RBC) deformation results in ATP release, and that platelets attenuate contraction force based on substrate stiffness. The objective of this proposal is thus to create microfluidic systems in which the biophysical and biochemical aspects of hematological processes can be independently investigated. More specifically, this proposal will present novel microfluidic devices: an “endothelial”-ized, T-junction to elucidate the biophysical processes that define the mechanism of action of the ferric chloride thrombosis model; a micropillar array to examine the physical effect of a geometrically relevant, non-biological matrix on platelet and RBC activity; and an electrospun fibrinogen mesh device and a micro-slit device to define the physical parameter space (shear, time of deformation, cell stiffness) that governs RBC fragmentation. Microfluidic platforms allow for real-time, microscopic evaluation of cell response (via brightfield morphology and immunostaining) and precise spatiotemporal control of system inputs and flow characteristics, including shear stress. The knowledge gained by successfully decoupling the biophysical and biological aspects of hematology can result in improved diagnostic assays for blood cell activity and new targets for therapeutics.