Advanced Microchannel Design with Obstacles for Enhanced Separation of Circulating Tumor Cells from Blood Cells

The efficient separation of circulating tumor cells (CTCs) from peripheral blood components is crucial for enhancing cancer diagnostics, developing targeted therapeutic approaches, and facilitating detailed cellular-level analyses. Inertial microfluidic channels have gained recognition as a highly promising platform owing to their straightforward design, capability to operate at high flow rates, and reliance on intrinsic hydrodynamic forces rather than external fields. However, unresolved issues persist, including the need to improve separation efficiency, sample purity, and processing throughput, while also reducing the cost of device fabrication. This study addresses these issues by introducing a novel microchannel design with strategically placed obstacles optimized through finite element method (FEM) simulations to achieve superior separation performance. The findings highlight the enhanced performance of an innovative inertial microfluidic platform incorporating rhomboid-shaped structures, specifically engineered to optimize the separation of CTCs. At an inlet flow rate of 0.33 mL/min, numerical simulations demonstrated that the rhomboid obstacle geometry achieved complete separation efficiency and purity (100%), surpassing the performance of other geometrical configurations. Experimental validation using MCF-7 and white blood cells (WBCs) further corroborated the simulation outcomes, yielding a separation efficiency of 98.3 ± 1.7% and a purity of 95.7 ± 3.8%. Optimal performance was achieved with 15 obstacle steps, where fewer steps led to significant drops in efficiency and purity. The design is cost-effective due to its reduced microchannel length, simplified geometry, and compatibility with standard fabrication techniques, while maintaining efficient throughput and high cell viability. The novel microchannel design represents a balanced performance in terms of throughput, separation efficiency, and device compactness. By integrating obstacle-based flow dynamics and computational optimization, the device offers a scalable solution for cancer diagnostics and cellular research. This work sets a new benchmark in particle separation technologies, contributing to advancements in biomedical and tissue engineering applications.