E. Bolea-Fernandez*, A. Bazo, A. Rua-Ibarz, M. Aramendía, M. Resano

University of Zaragoza, Department of Analytical Chemistry, Aragon Institute of Engineering Research (I3A), Zaragoza, Spain, 50009

*ebolea@unizar.es

Inductively coupled plasma-mass spectrometry (ICP-MS) is the most powerful technique for (ultra-)trace elemental analysis in a large variety of sample types.[1] Initially, the technique was developed to analyze homogeneous aqueous solutions. Today, it is also ideally suited for the analysis of discrete entities.[2] This methodology was first deployed for the analysis of colloids and nanoparticles (NPs), but over the last years, it has been realized that this approach could also be of more general application. Among the different available options, the analysis of individual cells via single-cell ICP-MS (SC-ICP-MS) is particularly noteworthy, given the possibility of obtaining the mass distribution of the analytes present in the cell.[3] SC-ICP-MS can also offer information about both the intra- and extra-cellular content, thus providing a more comprehensive picture. The characterization of NPs and the analysis of single cells share many similarities, but the level of understanding and the number of applications developed for both types of entities are very different, with the former being significantly more mature. A major drawback still hampering straightforward SC-ICP-MS analysis relates to the necessity of developing cell-specific calibration strategies, as the ones currently in use have been adopted from the former SP-ICP-MS approach,[4] without considering that both NPs and cells differ significantly.

In this work, novel calibration methods for SC-ICP-MS analysis have been explored. The fundamental principle of these approaches is to rely on entities (NPs), rather than on ionic standard solutions, for calibration. For method validation, we rely on the analysis of the SELM-1 cell certified reference material (NRC), consisting of selenium enriched yeast, and certified for total Se content (i.e., both intra- and extra-cellular Se).[5] By comparing the recovery values obtained in each case to the certified Se concentration of a suspension of SELM-1 reference material, the superior performance of novel transport-efficiency independent approaches has been demonstrated. These results call for a fundamental change, in which determination of the ionic contents should rely on calibration using ionic standard solutions, but determination of the elemental contents in discrete entities, such as cells, should ideally be based on calibration using standard entities – ions with ions, entities with entities.

References

[1] Van Acker et al.; Nat. Rev. Methods Primers, 2023, 3, 52.

[2] M. Resano et al.; Chem. Sci., 2022, 13, 4436-4473.

[3] T. Liu et al.; Anal. Chim. Acta, 2021, 1177, 338797.

[4] A. Bazo et al.; Anal. Chim. Acta, 2024, 1331, 343305.

[5] Z. Mester et al.; Anal. Bioanal. Chem., 2006, 385, 168-180.