Particle adhesion to tissue (vascular endothelium) depends critically upon particle/cell property (size, receptors), scale/geometric features of vasculature (diameter, bifurcation etc.) and local hemodynamic factors (stress, torque etc.). Current, in-vitro flow chambers suffer from serious limitations including (a) idealized, macrocirculatory scaling not representative of microvasculature (b) no representation of geometric features (bifurcations), healthy versus diseased vasculature and network of interconnects and (c) requirement of large volumes together with their non-disposable nature. We propose to develop and demonstrate a novel, comprehensive toolkit for studying cell/drug carrier adhesion comprising of (a) microfluidic, microvascular flow network chip, based on in-vivo images, with proven protocols to culture cells and (b) customized, easy-to-use CFD-based software to model flow, particle transport and adhesion in these chips. The microchannel network will be designed based on images of in-vivo microvascular images of small animals collected using ANET technique. The flow cell will be microfabricated using soft lithography techniques on disposable, inexpensive plastic (PDMS) substrate. Controlled experiments with microspheres will be used to demonstrate methodology and verify models. Confluent layer of endothelial cells will be cultured on the plastic microchip. Advanced models of flow/particle transport will be adapted for analysis of microvascular dynamics and an easy-to-use GUI interface developed. Phase II will focus on (a) expanding the network databases (include diseased states) (b) protocols, experiments with other cells/tumors and (c) software encapsulation. A multidisciplinary team (CFD Research Corp. and U. of Tennessee Health Science Center) has been assembled, which includes experts in microvascular imaging, microfabrication, microfluidics/cell-culture, CFD modeling and biorheology. Anticipated Benefits/Commercial Potential: The novel, anatomically realistic, microvascular network based flow-chip integrated with customized software can be used to examine particle cell -tissue interactions under controlled conditions that truly mimic the microvascular environment. The accompanying software tool will be critical in furthering fundamental understanding as well as planning of experiments. Spurred by the added functionality, drastic reduction in reagents/cells used and disposability (compared to the current simplistic, expensive flow chambers) the technology will be marketed to and expected to be adopted by researchers in a variety of biomedical & drug discovery research fields (encapsulated delivery therapies, tissue engineering, disease physiologic processes such as atherosclerosis etc.).
