Platinum-Chimeric Carrier Cells for Ultratrace Cell Analysis in Mass Cytometry

• Published in: Analytical chemistry (Washington) 2023-10, Vol.95 (40), p.14998-15007
• Main Authors: Li, Yiyang, Wang, Boqian, Ahmad Khan, Zara, He, Jie, Cheung, Edwin, Su, Wenqiong, Wang, Aiting, Jiang, Hui, Jiang, Lai, Ding, Xianting
• Format: Article
• Language: English
• Subjects: Amino acids; Biological properties; Biological samples; Biomarkers; Cell lines; Cisplatin; Cytometry; Dimensional analysis; Immune system; Peptides; Plasma membranes; Platinum; Proteins
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/acs.analchem.3c02706

Mass cytometry by time-of-flight (CyTOF), a high-dimensional single-cell analysis platform, detects up to 50 biomarkers at single-cell resolution. However, CyTOF analysis of biological samples with a minimal number of available cells or rare cell subsets remains a major technical challenge due to the extensive loss of cells during cell recovery, staining, and acquisition. Here, we introduce a platinum-chimeric carrier cell strategy for mass cytometry profiling of ultratrace cell samples. Cisplatin can rapidly enter broken plasma membranes of dead cells and form a chimeric interaction with cellular proteins, peptides, and amino acids. Thus, 198Pt-cisplatin is adopted to tag carrier cells in the pretreatment stage. We investigated 8 cell lines that are commonly accessible in laboratories for their potential as carrier cells to preserve rare target cells for CyTOF analysis. We designed a panel of 35 protein biomarkers to evaluate the comprehensive single-cell subtype classification capability with or without the carrier cell strategy. We further demonstrated the detection and analysis of as few as 1 × 104 immune cells using our method. The proposed method thus allows CyTOF analysis on precious clinical samples with less abundant cells.