Advances in Inductively Coupled Plasma-Mass Spectrometry for Detection of Endogenous and Exogenous Substances in Single Cells

Cells are the fundamental structural and functional units of biological organisms, with inherent differences in composition and interactions with exogenous substances, known as cellular heterogeneity. Single cell inductively coupled plasma-mass spectrometry (SC-ICP-MS) allows for the high-throughput introduction of individual cells, enabling the highly sensitive detection and quantification of elements within a single cell, thus effectively providing information on cellular heterogeneity. This review outlined the SC-ICP-MS sample preparation process for different types of cells (single-cell systems, aggregation-prone and adherent cell systems, animal tissues, and plant tissues), including steps such as separation, washing, and fixation, as well as the advantages and existing issues of the current sample introduction systems and quantification methods. The recent applications of SC-ICP-MS in detecting endogenous substances (endogenous elements and proteins), exogenous substances (heavy metals, metal-based drugs and nanoparticles), and the simultaneous detection of both endogenous and exogenous substances were summarized. Finally, the perspectives on the future development of SC-ICP-MS in analytical methods and application fields were presented, including the optimization of single-cell sample preparation, transport efficiency, evaluation standards of ionization efficiency, and the establishment of multiparametric cell analysis platforms.