Deterministic lateral displacement (DLD), which takes advantage of the asymmetric bifurcation of laminar flow around the embedded microposts, has shown promising capabilities in separating cells and particles of different sizes. Growing interest in utilizing high-throughput DLD devices for practical applications, such as circulating tumor cell separation, necessitates employing higher flow rates in these devices, leading to operating in moderate to high Reynolds number (Re) regimes. Despite extensive research on DLD devices in the creeping regime, limited research has focused on the physics of flow, critical size of the device, and deformable cell behavior in DLD devices at moderate to high Re. In this study, the transport behavior of particles/cells is investigated in realistic high-throughput DLD devices with hundreds of microposts by utilizing multiphysics modeling. A practical formula is proposed for the prediction of the device critical size, which could serve as a design guideline for high-throughput DLD devices. Then, the complex hydrodynamic interactions between a deformable cell and DLD post arrays are investigated. A dimensionless index is utilized for comparing different post designs to quantify the cell–post interaction. It is shown that the separation performances in high-throughput devices are highly affected by Re as well as the micropost shapes. These findings can be utilized for the design and optimization of high-throughput DLD microfluidic devices.

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