Inertia-magnetic microfluidics for rapid and high-purity separation of malignant tumor cells

Abstract

The existence of many background cells and the size overlap between white blood cells (WBCs) and malignant tumor cells (MTCs) pose a challenge for the efficient separation of MTCs from effusions or bloods. Herein, we proposed an inertia-magnetic cell separation (IMCS) device integrating a trapezoidal spiral chip with an immunomagnetic chip for high-throughput, high-recovery, and high-purity separation of MTCs from malignant pleural and peritoneal effusions (MPPEs). First, the effects of flow rate and particle size on separation performances in two separate chips were investigated. Then, the performances of the integrated IMCS device were characterized using blood samples spiked with three different tumor cells (A549, MCF-7, and MDA-MB-231 cells). The results showed that all the three tumor cells were separated from the WBCs with a high-throughput of ∼ 3200 μL/min, a high-recovery ratio of > 90%, and a high-purity of > 70%. Finally, we successfully separated MTCs from four clinical MPPE samples with an average purity of > 70%. As compared with conventional microfluidic devices using single technologies, our IMCS device combines the advantages of both passive size-dependent separation technology and immunomagnetic separation technology and can accurately separate tumor cells from WBCs of comparable sizes at a high throughput. Therefore, we envision that the high-purity MTC separation ability of our IMCS device can improve the sensitivity and efficiency of cytological examination.