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Device Design for Inducing Aneurysm-Susceptible Flow Conditions Onto Endothelial Cells

Abstract
Aneurysms are a deadly asymptomatic cardiovascular disease that may occur especially where there are bends and bifurcations in the cerebral vasculature. A region where these features are especially prominent is the Circle of Willis (COW) in the brain, where aneurysms are known to occur. In the carotid artery, which feeds into the COW, the Reynolds number of blood flow is typically around 200-500. Even with such a low Reynolds number, turbulent-like flow, or tortuous flow, can occur due to bends, bifurcations and highly pulsatile flow which lower the effective Reynolds number where tortuous flow can occur. Highly pulsatile flow is unsteady flow that is high in magnitude and changes over time. Endothelial cells (ECs) line the inner wall of the blood vessel and experience the friction force of blood flow. This work is focused on designing a device that can expose ECs to forces they would undergo in an aneurysm-susceptible site. This is accomplished by exposing ECs to physiologically relevant Wall Shear Stress (WSS) and vibrations simultaneously. Vibrations in the body occur due to flow separation at the vessel wall, which leads to pressure changes. These pressure changes induce vibrations onto ECs. The fluid flow in the designed Parallel Plate Flow Chamber (PPFC) is laminar to induce a predictable WSS onto the cells, while the vibrations will induce a rapid cyclical force to simulate pressure fluctuations that may occur in vivo. The aneurysm-susceptible flow will simulate a more turbulent-like flow in the carotid artery; higher maximum WSS (around 2.2 Pa) with vibrations. The aneurysm-protective flow will have a lower WSS maximum (around 0.5 Pa). The PPFC, made of polycarbonate, is small and light enough to be conveniently vibrated using an electromagnetic vibration stage. The PPFC can be driven by a syringe or peristaltic pump, allowing for either steady or transient waveforms. The PPFC’s fluid domain will not change upon vibration, isolating the effect of vibration on the cells. Also, two side-by-side glass slide slots were included to allow for both protein and mRNA quantification from the same experiment, increasing experimental efficiency and flow-related consistency between the two cell areas. Simulations using ANSYS Fluent verified the flow field and WSS waveform on the cells for the designed geometry for 3D and 2D cases, as well as verified equal WSS values throughout all areas of ECs. Then, Particle Image Velocimetry (PIV) was done to verify the predicted flow rate in the machined PPFC given a steady flow rate driven by a syringe pump. Preliminary cell experiments were performed in an incubator under flow and vibration conditions to demonstrate cell survivability.
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