The migration of living cells plays an important role in immune response, hemostasis, cancer progression, delivery of nutrients, and microfluidic technologies such cell separation/enrichment and flow cytometry. Using three-dimensional computational algorithm for multiphase viscoelastic flow and mass transport, this study is focused on the investigation of the effects of cell size, viscoelasticity, cortical tension, fluid inertia and cell-cell interaction on passive migration and deformation of leukocytes, and active deformation of circulating cells during chemotactic migration in a rectangular microchannel. The results of the passive migration modeling show that there is an almost linear increase in the distance between the wall and the lateral equilibrium position of liquid drops or leukocytes with the particle diameter-to-channel height ratio increased from 0.1 to 0.5. Drops with different bulk viscosities can be efficiently separated if their interfacial tension is low or the flow rate is sufficiently high. The microfluidic technology is well suited for the separation of leukocytes with different cytoplasmic viscosities and relaxation times, but it is much less sensitive to cortical tension. When a series of closely spaced cells with same size are considered, they generally undergo damped oscillation in both lateral and translational directions until they reach equilibrium positions where they become evenly distributed in the flow direction (self-assembly phenomenon). For a series of cells with different sizes, bigger cells could collide repeatedly with smaller ones and enter the other side of the channel (above or below the centerline). For a series of cells with different deformability, more deformable cells upon impact with less deformable cells move to an equilibrium position closer to the centerline. The results of our study provide better understanding of cell margination in bloodstream and cell separation/enrichment in microfluidic devices. The simulation data on active migration of cells show the formation of a finger- or lamellipodium-like projection of the cell membrane towards the chemoattractant source and indicate that lowering the cortical tension facilitates cell protrusion. / acase@tulane.edu