Sinuspiral Microchannel: A Novel Inertial Microfluidic Device for High-Efficiency Isolation of Circulating Tumor Cells

Abstract

Abstract Effective separation of circulating tumor cells (CTCs) from white blood cells (WBCs) plays a vital role in enhancing cancer diagnosis, assessing treatment effectiveness, and promoting progress in personalized medicine development. Inertial microfluidic systems have recently emerged as an attractive method for cell sorting, offering marker-independent and large-scale separation performance while maintaining the physiological integrity of the cells. Nevertheless, traditional designs often encounter trade-offs between separation performance, flow stability, and device compactness. To address these limitations, the present research proposes a novel microfluidic platform, named Sinuspiral, which is designed with optimized geometrical features to improve the efficiency of CTC separation. The proposed microchannel was optimized using finite element method (FEM) simulations, where key parameters─including inlet flow rates, aspect ratio, U-shaped curvature radius, radius ratio, and number of loops─were systematically analyzed to maximize separation performance. Simulation outcomes revealed that the influence of curvature and the induced secondary flow structures are essential for attaining precise, size-dependent cell separation. When functioning at optimal parameters─comprising a sample flow rate of 0.09 mL/min, a sheath flow rate of 0.18 mL/min, an aspect ratio of 0.5, a U-shaped curvature radius of 100 μm, a radius ratio of 0.03, and seven channel loops─the developed microchannel achieved a separation purity and efficiency of 100% in simulation analyses. Experimental verification conducted with manufactured Sinuspiral microchips and biological samples comprising WBCs and MCF-7 cells (serving as CTC models) demonstrated the device’s strong operational capability, attaining a separation purity of 93.0 ± 2.7% and an efficiency of 96.7 ± 1.6%. These findings highlight the Sinuspiral system’s promise as a highly efficient and economically viable platform for isolating rare circulating cells. This study lays the groundwork for future progress in inertial microfluidic technologies, offering a practical and efficient platform for biomedical and clinical uses, with specific significance for CTC enrichment and cancer diagnosis.