Ambient mass spectrometry-based detection system for tumor cells in human blood

Circulating tumor cells (CTCs) are a rare cell population in peripheral blood that lead to distant metastasis in many types of cancer. Most current CTC-detection methods, including antibody-based detection, have shortcomings such as false-positive and false-negative findings. These limitations must be addressed to achieve CTC detection with high accuracy and reproducibility; and therefore, clinical utility. Herein, we propose a novel method of tumor cell detection in human blood samples using ambient mass spectrometry (MS). Probe electrospray ionization (PESI)-MS was used to obtain mass spectra containing 1,136 peaks from peripheral blood mononuclear cells (PBMCs) spiked with different numbers of SAS tumor cells by. Similarities between the spectral patterns of PBMCs spiked with different numbers of tumor cells, and those from PBMCs alone, were statistically reduced with increasing numbers of SAS tumor cells. Intriguingly, the influences of a few hundred tumor cells could be observed in the changes to the spectral peaks of PBMCs. Moreover, 16 individual peaks, with positive and negative correlations between peak intensities and the number of SAS tumor cells, were identified as tumor-associated metabolites. In conclusion, we successfully used PESI-MS to detect tumor cells present among very large numbers of PBMCs without the need for enrichment using antibodies for tumor cell markers. Our data strongly suggest that this method may be clinically suitable for CTC detection.