Computational Fluid Dynamics Simulations at Micro-Scale Stenosis for Microfluidic Thrombosis Model Characterization

Abstract

Platelet aggregation plays a central role in pathological thrombosis, preventing healthy physiological blood flow within the circulatory system. For decades, it was believed that platelet aggregation was primarily driven by soluble agonists such as thrombin, adenosine diphosphate and thromboxane A2. However, recent experimental findings have unveiled an intriguing but complementary biomechanical mechanism—the shear rate gradients generated from flow disturbance occurring at sites of blood vessel narrowing, otherwise known as stenosis, may rapidly trigger platelet recruitment and subsequent aggregation. In our Nature Materials 2019 paper [1], we employed microfluidic devices which incorporated micro-scale stenoses to elucidate the molecular insights underlying the prothrombotic effect of blood flow disturbance. Nevertheless, the rheological mechanisms associated with this stenotic microfluidic device are poorly characterized. To this end, we developed a computational fluid dynamics (CFD) simulation approach to systematically analyze the hemodynamic influence of bulk flow mechanics and flow medium. Grid sensitivity studies were performed to ensure accurate and reliable results. Interestingly, the peak shear rate was significantly reduced with the device thickness, suggesting that fabrication of microfluidic devices should retain thicknesses greater than 50 µm to avoid unexpected hemodynamic aberration, despite thicker devices raising the cost of materials and processing time of photolithography. Overall, as many groups in the field have designed microfluidic devices to recapitulate the effect of shear rate gradients and investigate platelet aggregation, our numerical simulation study serves as a guideline for rigorous design and fabrication of microfluidic thrombosis models.