High‐Sensitive Mass Cytometry Metal Tags Based on Noble Metal Nanoparticles Assisting Acute Myeloid Leukemia Immune Checkpoint Profiling

Mass cytometry is optimal for acute leukemia immune checkpoint profiling. However, current commercial metal-chelating polymer (MCP) metal tags limit its sensitivity due to low metal loading capacity. We report a novel synthetic strategy employing antibody-conjugated gold or platinum nanoparticles (AuNP/PtNP) for high-dimensional single-cell immunophenotyping in both single cell suspension mass cytometry and imaging mass cytometry. Extremely low-dose AuNP (34 NPs/cell) exhibited MCP-comparable sensitivity, while high doses enabled up to 48-fold signal amplification. Furthermore, integration of the detection of low-abundance TIGIT and OX40 by AuNP/PtNP tags and other 22 biomarkers by MCP tags, three significantly distinct T cell subpopulations in healthy donor and acute myeloid leukemia samples were identified, providing new targets and intervention strategies for the diagnosis and treatment of acute myeloid leukemia. The proposed strategies demonstrate that noble metal NP-based tags show promising potential in detection of low-abundance cell surface biomarkers and enhance MC implementation in both biomedical and clinical applications.