S. Hymel, H. Fujioka, D. Khismatullin
Tulane University,
United States
Keywords: cell sorting, cell separation, deformability, microfluidics, pillars
Summary:
Embedded pillar microstructures have been shown to be an efficient approach for controlling and sculpting shear flow in a microchannel (1, 2), but it is not yet demonstrated to be effective for cell sorting and, in particular, for the separation of circulating cells with different size and deformability (3, 4). Experiments with rigid particles passing through a sequence of longitudinally spaced pillars indicate that pillars can improve lateral (perpendicular to the flow) separation of cells (4). In order to achieve efficient cell sorting, longitudinal spacing, lateral location, and the number of pillars need to be optimized via computational fluid dynamics (CFD) that accounts for complex microchannel geometry and cell deformability. In this study, we used our custom computational algorithm for deformable cell migration (VECAM) (5, 6) to study these effects on the lateral separation of cells with different elasticity and size in a rectangular microchannel. The geometry of the VECAM computational domain is customizable, e.g., it can be reconstructed from a microchannel image (Fig. 1). Using VECAM, we modeled a pairwise migration of viscoelastic cells in a microchannel that has a sequence of pillars with a circular cross-section. For size- or deformability-based cell separation in a microchannel, the following criteria were used: 1) the lateral separation distance should be large enough to trap the cells with different properties at the channel outlet; and 2) lateral separation distance should be an increasing function of the cell-to-cell diameter and/or shear elasticity ratios. The former criterion is well established, but a little attention was placed on the latter, which has a key role in cell separation. If the separation distance is large but decreases with the ratio of mechanical properties (“negative trend”), identical cells will be separated, while the cells with different properties will be mixed near the flow centerline. Based on those criteria, our computational study revealed two basic pillar configurations optimized for deformability-based separation: 1) “duplet” that consists of two closely spaced pillars positioned far below the centerline and above the centerline halfway to the wall (Fig. 2); and 2) “triplet” composed of three widely-spaced pillars located below, above and at the centerline, respectively (Fig. 3). The duplet configuration is well suited for deformable cell separation in short channels, while the triplet or a combination of duplets and triplets provides even better separation in long channels. Using these optimized pillar microstructures can improve microfluidic sorting and isolation of blood and rare circulating tumor cells.