Abstract：Highly sensitive techniques for biomolecules detection play important roles in the elucidation of molecular mechanisms and early diagnosisof many diseases, because many specific functions of cells and tissues are determined by biomoleculescontent under different physiological conditions, while even a few molecules may be sufficient to trigger pathophysiological processes and affect the biological functions of cells. Metal stable isotopes are similar with radioactive isotopes in chemical properties. After labeled with metal stable isotopes, multiple biomolecules can be detected simultaneously by elemental mass spectrometry with high sensitivity. As an accurate detector for inorganic elements, the advantages of ICPMS include low detection limit, low matrix effect, wide dynamic range, and high spectral resolution for isotopes, which is applicable for metal stable isotope tagging-based bioassay. Metal stable isotope tagging has been successfully applied for the detection of proteins, nucleic acids, enzyme activity, small biomolecules, andeven single cells, demonstrating great potential in bioassay. Despite a series of excellent reviews about metal stable isotope tagging have been presented recently, most of them were not in Chinese. Herein, to promote the related research, we briefly introduce the progress of metal stable isotope tagging-based bioassay in this review. The main contents include: metal stable isotope detection tool-elemental mass spectrometry, sensitive bioassay, multiple biomolecules simultaneous analysis, accurate bioassay, and single cell analysis based on metal stable isotope tagging. Metal stable isotope tagging has three distinct characteristics: high sensitivity-most metal stable isotopes possess high tagging sensitivity, and signal amplification can be achieved by metal nanomaterial tagging etc.; simultaneous multiplex analysis- high resolution isotope line of mass spectrometer provides multiplex analysis capability; high accuracy-isotope dilution method provides traceability to International System of Units.
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