Multiplexed serpentine microchannels for high-throughput sorting of disseminated tumor cells from malignant pleural effusion

Abstract

Accurate isolation and detection of disseminated tumor cells from the malignant pleural effusion (MPE) is of significant clinical importance. Cytology is a routine diagnostic tool for the analysis of MPE. However, its sensitivity is limited by the existence of a significant number of contaminating blood cells and relatively small and even rare number of target tumor cells in the effusion. To address this limitation, we proposed and developed multiplexed inertial microfluidic devices for fast and efficient isolation and purification of tumor cells from a large volume (> 50 mL) of pleural effusion sample in a label-free way. The rare tumor cells were separated from blood cells relying on the mechanism of size-based differential inertial focusing. The inertial focusing and separation performance of the single serpentine channel was characterized using polystyrene beads and cancer cells lines (A549 and MCF-7) spiked in blood. Subsequently, the multiplexed devices were developed by parallelizing serpentine channels in both planar and vertical directions (e.g., 8 and 24 parallel channel) and the separation was evaluated by the spiked tumor cells (recovery ratio ∼ 80 % for the 8-channel device). Finally, we validated the performance of the multiplexed device using the clinical pleural effusion samples. Malignant tumor cells (MTCs) with a concentration of 49–4806 counts/mL were detected in all 5 pleural effusion samples, with an average purity of ∼30 %. We envision that the multiplexed device is a promising disposable tool towards the clinical applications, given the superiorities of simple structure, high throughput, low cost and good efficiency.