Facile Cascaded Negative Magnetophoresis Chip Combined with ICP-MS for Efficient Sorting and Online Detection of Circulating Tumor Cells

The isolation and detection of circulating tumor cells (CTCs) play a significant role in early cancer diagnosis and prognosis. Negative magnetophoresis sorting is a label-free method, providing easy access to enrich intact and viable CTCs, but it struggles to meet the demands of high-throughput separation and direct downstream analysis. In this work, a facile cascaded negative magnetophoresis microfluidic chip was fabricated and online coupled to inductively coupled plasma mass spectrometry (ICP-MS) for the rapid separation and detection of rare CTCs in blood samples. The chip consisted of two parts: a negative magnetophoresis sorting zone and a negative magnetophoresis phase-transfer zone. In the sorting zone, WBCs labeled with anti-CD45-magnetic beads (MBs) dispersed in biocompatible ferrofluid were removed by magnetic attractive force, while CTCs labeled with anti-EpCAM-Eu migrated into the phase-transfer zone by magnetic repulsive force; in the phase-transfer zone, due to the stable laminar flow formed by the magnetic fluid and PBS buffer, CTCs migrated into the PBS under both the magnetic repulsive force and inertial lift force and online introduced into ICP-MS for detection. This device can achieve CTC enrichment at a high throughput of 100 mu L min-1 and has the capability for direct downstream analysis and recultivation (cell viability of 99.27%). The method was applied for the detection of CTCs in real clinical blood samples from 10 patients diagnosed with various cancers, and the detection rate was 100%, providing a simple and efficient approach for clinical detection of rare CTCs.