High-Throughput Separation and Enrichment of Rare Malignant Tumor Cells from Large-Volume Effusions by Inertial Microfluidics.

Abstract

Detection of malignant tumor cells (MTCs) in pleural effusions is essential for determining the malignancy. However, the sensitivity of MTC detection is significantly decreased due to the existence of a massive number of background blood cells in large-volume samples. Herein, we provide a method for on-chip separation and enrichment of MTCs from malignant pleural effusions (MPEs) by integrating an inertial microfluidic sorter with an inertial microfluidic concentrator. The designed sorter and concentrator are capable of focusing cells toward the specified equilibrium positions by inducing intrinsic hydrodynamic forces, enabling the size-based sorting of cells and the removal of cell-free fluids for cell enrichment. A 99.9% removal of background cells and a nearly 1400-fold ultrahigh enrichment of MTCs from large-volume MPEs can be achieved by this method. The concentrated high-purity MTC solution can be used directly for cytological examination by immunofluorescence staining, enhancing the accurate identification of MPEs. The proposed method can also be employed for the detection and count of rare cells in various clinical samples.