Deep-coverage single-cell metabolomics enabled by ion mobility-resolved mass cytometry

作者：Mingdu Luo, Tianzhang Kou, Yandong Yin, S. Kevin Zhou, Xiaolan Zhu, Xinhao Zeng, Junhao Hu, Zheng‐Jiang Zhu · 发表于：Nature Methods · 年份：2026 · DOI：10.1038/s41592-025-02970-2 · 被引用次数：5 · 研究领域：Single-cell and spatial transcriptomics、Metabolomics and Mass Spectrometry Studies、Cell Image Analysis Techniques

Current single-cell metabolomics approaches are limited by insufficient sensitivity, robustness and metabolite coverage. We present an ion mobility-resolved mass cytometry technology that integrates high-throughput single-cell injection with ion mobility-mass spectrometry for multidimensional metabolomic profiling. Ion mobility-enabled selective ion accumulation and cell superposition-based amplification strategies substantially enhance sensitivity, robustness and overall analytical performance. Combined with our computational tool, MetCell, this technology allows high-throughput analysis while achieving exceptional profiling depth, detecting over 5,000 metabolic peaks and annotating approximately 800 metabolites per cell-representing a 3-fold to 10-fold improvement over existing methods. It offers attomole-level sensitivity and captures a broad dynamic range of metabolites within individual cells. Applied to 45,603 primary liver cells from aging mice, it enabled accurate cell-type and cell-subtype annotation and revealed distinct metabolic states and heterogeneity in hepatocytes during aging. This platform sets a new benchmark for high-throughput single-cell metabolomics, advancing our understanding of metabolic heterogeneity at single-cell resolution.