Fast Screening of Circulating Tumor Cells in Blood Samples by Sialic Acid Recognition and Microfluidic Chip-Single-Cell ICP-MS: A Breakthrough in Non-invasive Cancer Diagnosis

Circulating tumor cells (CTCs) hold promise for non-invasive cancer diagnostics, but current detection methods face challenges like white blood cell (WBC) interference, high false negative rates, low throughput, and operational complexity. To overcome these, we developed a simple, fast, and universal CTCs analysis method by the integrating sialic acid (SA) recognition strategy, microfluidic cell sorting, and online single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS) detection. Cells from lysed blood sample were labeled by phenylboronic acid-functionalized gold nanoparticles (PBA-AuNPs) via PBA-SA recognition. Massive WBCs can be removed by the simply designed multi-flow microfluidic chip based on size-dependent inertial migration, and target CTCs can be further distinguished from the rest WBCs by monitoring the 197 Au signals on cells the by SC-ICP-MS detection due to overexpression of SA on tumor-shed CTCs. The developed method is able to quickly screen different types of epithelial- and mesodermal-derived CTCs with a throughput of 10 min per sample and limits of detection as low as 28 cell/mL. This method has been applied to the detection of CTCs in real blood samples from cancer patients with different cancer types as well as measuring the distribution of single-cell membrane SA expression, offering a simple and fast screening tool for cancer diagnosis and monitoring.