Curved Omega: A High-Performance and Cost-Effective Microfluidic Platform for Circulating Tumor Cell Isolation

Abstract

The reliable separation of circulating tumor cells (CTCs) from peripheral blood is essential for the detection of cancer at an early stage, assessment of treatment effectiveness, and realization of personalized medicine approaches. Inertial microfluidics has become one promising technique because of its ability to provide a high-throughput process along with label-free manipulation. Nevertheless, conventional devices are frequently hindered by limitations including limited efficiency of isolation, vulnerability to flow instability, and difficulties with scaling up. To address these challenges, the current research investigates a curved Omega inertial microfluidic architecture that employs a curved spiral geometry with repeated Omega-shaped sections to enhance CTC separation. In this case, the proposed microdevice was developed through comprehensive finite element method (FEM) simulations and surrogate modeling analysis of important design factors, including flow rates at the inlets, aspect ratio (AR), microchannel radius (R1), and Omega radius (R2). As a result, a more effective separation along with increased purity of collected samples were obtained for optimal configurations (sample flow rate: 0.94 mL/min; sheath flow rate: 1.56 mL/min; R1 = 4.0 mm, R2 = 0.5 mm, AR = 0.5) with 100% numerical separation efficiency and purity. The performance of the proposed microfluidic system was experimentally evaluated using fabricated microfluidic devices and 4′,6-diamidino-2-phenylindole (DAPI)-stained MCF-7 cancer cells as CTC models. A separation efficiency of 93.3% and a purity rate of 91.7% were observed from the experiment. In addition, approximately 94% of the examined postseparation MCF-7 cells remained attached and exhibited spread morphology consistent with short-term viability after 48 h of culture. The separation mechanism of the curved Omega platform is label-free and relies on passive hydrodynamic forces without external field-based actuation; however, the experimental validation in this study involved a 40-fold dilution of the blood sample with phosphate-buffered saline (PBS) as a sample-preparation step.