The migration and transformation of trace elements in living organisms are critical to various physiological processes. Analyzing trace elements at the cellular level is essential for understanding their functional roles in biological systems. Unlike conventional bulk analysis, single-cell analysis can reveal cell heterogeneity, providing significant insights in biological research.

A notable technique for single-cell analysis is time-resolved inductively coupled plasma-mass spectrometry (TRA-ICP-MS). Houk’s group [1] investigated the behavior of bacterium grown in a uranium-spiked medium by TRA-ICP-MS, and observed distinct uranium spikes in the presence of intact bacteria, but not in aqueous uranium solution. Similarly, Ho and Chan [2] measured Mg, Mn and Cu in single algal cells by TRA-ICP-MS, observing signal spikes corresponding to individual cells, with the frequency of these spikes proportional to the number of cells. These pilot works highlight TRA-ICP-MS as an emerging tool for counting cells and quantifying elements within them.

TRA-ICP-MS has increasingly been used for evaluating cell-to-cell differences in elemental content, as well as the cellular uptake of metal-containing drugs and nanoparticles in the fields of environment, pharmaceuticals, biology and toxicology. However, several challenges remain in TRA-ICP-MS based single-cell analysis, including: (1) low detection efficiency; (2) The possibility of signal events originating from multiple cells when using diluted cell suspensions; (3) intrinsic limitations of ICP-MS, such as its destructive nature, lack of spatial and morphological resolution, and inability to provide elemental species information. Significant efforts have been made to enhance the performance of TRA-ICP-MS in single-cell analysis, focusing on three main areas: (1) Improvement in ICP-MS instrumentation; (2) Combination with microfluidic platform; (3) Development of new methodologies and their applications.

Microfluidic chips are particularly well-suited for cell manipulation, such as encapsulation of single cell in droplets, ordering cells into a single stream, etc. The development of new methods combining microfluidic chip with ICP-MS will provide more valuable information for single cell analysis. In this presentation, the potential of microfluidic chips combined with ICP-MS for single cell analysis will be illustrated [3-7].

References

[1] F. Li, D. W. Armstrong, R. S. Houk, Anal. Chem. 2005, 77, 1407-1413.

[2] K. S. Ho, W. T. Chan. J. Anal. At. Spectrom. 2010, 25, 1114-1122.

[3] H. Wang, B.B. Chen, M. He, B. Hu, Anal. Chem. 2017, 89, 4931-4938.

[4] X.X. Yu, B.B. Chen, M. He, H. Wang, B. Hu, Anal. Chem. 2019, 91, 2869-2875.

[5] X.X. Yu, B.B. Chen, M. He, B. Hu, Anal. Chem. 2020, 92, 13550-13557.

[6] Z. N. Chen, B.B. Chen, M. He, B. Hu, Anal. Chem. 2020, 92, 12208-12215.

[7] Z. N. Chen, B.B. Chen, M. He, B. Hu, Anal. Chem. 2022, 94, 6649-6656