细胞和组织的很多特定功能都由其在不同的生理条件下的生物分子含量决定, 极少数分子的改变就有可能影响细胞生物功能并触发疾病生理过程, 因此高灵敏的生物分子检测技术在疾病机理研究和疾病早期诊断方面具有重要作用。 金属稳定同位素和放射同位素化学性质相近, 借鉴放射同位素标记的成功经验, 通过金属稳定同位素标记多组分生物分子, 可以用原子质谱高灵敏地检测多组分生物分子。 作为灵敏准确的金属元素检测工具, 电感耦合等离子体质谱检出限低、 基体效应低、 线性范围广、 同位素谱线分辨率高, 因此适用于金属元素标记生物分子检测。 金属稳定同位素标记已经被广泛应用到蛋白质、 核酸、 酶活性、 生物小分子、 甚至单个细胞的检测中, 取得了一些可喜的进展, 并展现了广阔未来应用前景。 金属稳定同位素标记生物分析方法有三个特性: 高灵敏度-大多数金属的稳定同位素有较高的标记灵敏度, 并且可以通过纳米材料标记等方法实现信号放大; 多组分同时分析-质谱仪同位素谱线高分辨率提供了多组分分析能力; 高准确度-同位素稀释法提供了可溯源到SI国际单位制的高准确度检测结果。 为了更好的推动相关研究, 简要介绍金属稳定同位素标记生物分析的进展, 主要内容包括以下几个部分: 金属稳定同位素检测工具-无机质谱、 金属稳定同位素标记高灵敏度分析、 金属稳定同位素标记多组分同时分析、 金属稳定同位素标记高准确度分析、 金属稳定同位素标记单细胞分析的进展。

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.