Robust and efficient separation of white blood cells from blood using a microfluidic chip with a pair of linearly tapered crossflow filter arrays

Abstract

Clinical and immunological assays of white blood cells (WBCs) in human peripheral blood are of significance for disease diagnosis and immunological studies. However, separating WBCs from blood with high recovery and high purity remains challenging. In this study, by incorporating a pair of linearly tapered filter arrays, a crossflow filtration-based microfluidic chip was designed and fabricated for separation of WBCs from blood. The implementation of the linearly tapered filter arrays not only ensures a minimal and consistent flow through each sieve, but also achieves a high filtration ratio (~ 19). The validity and robustness of this straightforward design were substantiated through theoretical analysis, simulations, and model microparticle tests. The microfluidic chip achieved an almost perfect (> 99.2%) recovery and a ~ 20-fold enrichment of the targeted 8 μm particles (as surrogates for WBCs) from undesired 2 μm particles (as substitutes for red blood cells, RBCs) at flow rates ranging from 50 to 200 μL/min, irrespective of the filter array length and particle concentration. When applied to a twenty times diluted blood sample, the chip achieved a 96.6% recovery and 19.7-fold enrichment of WBCs, as well as a 95.0% removal of RBCs, at the optimal flow rate of 100 μL/min. With its simple design, cost-effectiveness, high recovery, substantial enrichment ratio, and considerable throughput, this chip offers an alternative solution that is potentially applicable to scenarios involving the separation of WBCs as well as other particles/cells.

Keywords: Crossflow filtration; Microfluidic chip; Particle separation; White blood cells.