High-throughput and high-purity separation of malignant tumor cells in pleural and peritoneal effusions using interfacial elasto-inertial microfluidics

Abstract

Efficient separation of exfoliated malignant tumor cells (MTCs) from pleural and peritoneal effusions is critical for improving the detection sensitivity and reducing the time consumed for cytological assessment. Herein, an interfacial elasto-inertial microfluidic device was developed for the high-throughput and high-purity separation of MTCs from malignant pleural and peritoneal effusions. Through using hyaluronic acid as an elastic enhancer, a high sample throughput of 120 μL min⁻¹ could be achieved. We first explored the effects of the flow-rate ratio and flow rate on particle separation. The results indicated that stable particle separation could be achieved over wide flow rates. We next characterized the device separation performance using blood samples spiked with various tumor cells (A549, MCF-7, and MDA-MB-231 cells) of different concentrations. A removal ratio of blood cells of over 99.8%, an average recovery ratio of tumor cells of 94%, and an average purity of tumor cells as high as 40% could be successfully achieved in a high-throughput and label-free manner. Finally, we successfully applied our device for the separation of MTCs in clinical pleural and peritoneal effusions from patients of different cancers. Our interfacial elasto-inertial microfluidic device may provide a potential sample preparation tool for cytological diagnosis of pleural and peritoneal effusions.