Improving liquid cancer biopsy through computer-aided microfluidic device design based on the tubular pinch effect and Deans flow

Abstract

A blood test, called a liquid biopsy is being developed by several research groups for the early detection of cancer. The key challenge in this process is enrichment, or isolation, of the small number of cancer cells in blood serum from other cells. This study uses numerical simulations to design devices that advance the state of art in the enrichment of circulating cancer cells. In particular, the lift forces acting on neutrally buoyant small spherical particles in a Poiseuille flow bounded by a wall are modelled using numerical computation. Specifically, we explore the influence of the Reynolds number, distance to the wall, and particle size on these lift forces, building upon previous research on the Segre-Silberberg effect. By validating the mechanism by which particles concentrate at specific positions within the fluid, we confirm the existence of the Segre-Silberberg effect in this system. Subsequently, we apply a customized 3D model of a filtration device to investigate the Segre-Silberberg effect and Deans effect in a non-Poiseuille flow, which can be applied in liquid cancer biopsy. Our results demonstrate that this flow pattern could potentially be used to separate cancer cells from the mean flow. Finally, we apply the flow separation mechanisms in microfluidic design through a rapid 3D design and computational fluid dynamics (CFD) verification cycle. The popular spiral microfluidic design does not demonstrate strong flow separation pattern in our tests, while the sinusoidal design shows much more promise. Further research is needed to empirically evaluate these designs.