Recent numerical analyses to optimize the design of microfluidic devices for more effective entrapment or segregation of surrogate circulating tumor cells (CTCs) from healthy cells have been reported in the literature without concurrently accommodating the non-Newtonian nature of the body fluid and the non-uniform geometric shapes of the CTCs. Through a series of two-dimensional proof-of-concept simulations with increased levels of complexity (e.g., number of particles, inline obstacles), we investigated the validity of the assumptions of the Newtonian fluid behavior for pseudoplastic fluids and the circular particle shape for different-shaped particles (DSPs) in the context of microfluidics-facilitated shape-based segregation of particles. Simulations with a single DSP revealed that even in the absence of internal geometric complexities of a microfluidics channel, the aforementioned assumptions led to 0.11-0.21W (W is the channel length) errors in lateral displacements of DSPs, up to 3-20% errors in their velocities, and 3-5% errors in their travel times. When these assumptions were applied in simulations involving multiple DSPs in inertial microfluidics with inline obstacles, errors in the lateral displacements of DSPs were as high as 0.78W and in their travel times up to 23%, which led to different (un)symmetric flow and segregation patterns of DSPs. Thus, the fluid type and particle shape should be included in numerical models and experiments to assess the performance of microfluidics for targeted cell (e.g., CTCs) harvesting.

15 pages, 6 figures