An Integrated\nInertial-Magnetophoresis Microfluidic\nChip Online-Coupled with ICP-MS for Rapid Separation and Precise Detection\nof Circulating Tumor Cells

Circulating tumor cells (CTCs) are recognized as promising\ntargets\nfor liquid biopsy, which play an important role in early diagnosis\nand efficacy monitoring of cancer. However, due to the extreme scarcity\nof CTCs and partial size overlap between CTCs and white blood cells\n(WBCs), the separation and detection of CTCs from blood remain a big\nchallenge. To address this issue, we fabricated a microfluidic chip\nby integrating a passive contraction–expansion array (CEA)\ninertial sorting zone and an active magnetophoresis zone with the\ntrapezoidal groove and online coupled it with inductively coupled\nplasma mass spectrometry (ICP-MS) for rapid separation and precise\ndetection of MCF-7 cells (as a model CTC) in blood samples. In the\nintegrated microfluidic chip, most of the small-sized WBCs can be\nrapidly removed in the circular CEA inertial sorter, while the rest\nof the magnetically labeled WBCs can be further captured in the trapezoidal\ngroove under the magnetic field. As a result, the rapid separation\nof MCF-7 cells from blood samples was achieved with an average recovery\nof 91.6% at a sample flow rate of 200 μL min<sup>–1</sup>. The developed online integrated inertial-magnetophoresis microfluidic\nchip-ICP-MS system has been applied for the detection of CTCs in real\nclinical blood samples with a fast analysis speed (5 min per 1 mL\nblood). CTCs were detected in all 24 blood samples from patients with\ndifferent types of cancer, exhibiting excellent application potential\nin clinical diagnosis.