Modeling of Deformable Cell Separation in a Microchannel with Sequenced Pillars

Abstract

Embedded pillar microstructures are an efficient approach for controlling and sculpting shear flow in a microchannel but have not yet demonstrated to be effective for deformability-based cell separation and sorting. Although simple pillar configurations (lattice, line sequence) worked well for size-based separation of rigid particles, they had a low separation efficiency for circulating cells. The objective of this study was to optimize sequenced microstructures for separation of deformable cells. This was achieved by numerical analysis of pairwise cell migration in a microchannel with multiple pillars, which size, longitudinal spacing, and lateral location as well as the cell elasticity and size varied. This 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; and 2) "triplet" composed of three widely-spaced pillars located below, above and at the centerline, respectively. 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. These optimized pillar microstructures can dramatically improve microfluidic methods for sorting and isolation of blood and rare circulating tumor cells.