Selective capture of target cells from whole blood in microfluidic systems is essential for clinical diagnosis and basic research (e.g., genomic and proteomic characterization). However, the efficiency of capturing rare cells such as circulating tumor cells or stem cells via microfluidic systems is low. Although studies have shown that increasing wall shear stress can reduce cell capture efficiency, the underlying mechanisms are not yet clear. Here, we developed a theoretical model to understand how parameters such as shear stress, cell properties and microchannel height affect cell detachment, which is a key factor causing reduced cell capture efficiency. In this model, we used a front tracking method to track cell deformation and calculate elastic force acting on cell membrane. We also employed adhesion dynamic simulation to calculate the adhesion force between capturing agents (e.g., antibody) and target cells. With these two methods, we simulated cell detachment under parabolic shear flows and investigated effects of mechanical parameters (shear stress, viscosities of cytoplasm and nucleus, elastic properties of cell membrane) and the ratio of cell radius to microchannel height on cell detachment. Cell detachment rate increased exponentially with increasing wall shear stress. In addition, a higher viscosity of intracellular fluid results in lower critical wall shear stress for cell detachment, dramatically reducing cell detachment rate. Microchannel height did not significantly affect cell detachment, especially when the ratio of cell radius to channel height is below 0.1. These results indicate the capability of the developed theoretical model to improve the design of microfluidic systems and operation conditions to reduce cell detachment, and thus improve cell capture efficiency. (C) 2013 Elsevier Ltd. All rights reserved.