High resolution imaging and 3D analysis of Ag nanoparticles in cells with ToF-SIMS and delayed extraction

Within this study, the authors use human mesenchymal stem cells incubated with silver nanoparticles (AgNPs) as a model system to systematically investigate the advantages and drawbacks of the fast imaging delayed extraction mode for two-dimensional and three-dimensional (3D) analyses at the cellular level. The authors compare the delayed extraction mode with commonly employed measurement modes in terms of mass and lateral resolution, intensity, and dose density. Using the delayed extraction mode for single cell analysis, a high mass resolution up to 4000 at m/z = 184.08 combined with a lateral resolution up to 360 nm is achieved. Furthermore, the authors perform 3D analyses with Ar-clusters (10 keV) and O₂⁺ (500 eV) as sputter species, combined with Bi₃⁺ and delayed extraction for analysis. Cell compartments like the nucleus are visualized in 3D, whereas no realistic 3D reconstruction of intracellular AgNP is possible due to the different sputter rates of inorganic and organic cell materials. Furthermore, the authors show that the sputter yield of Ag increases with the decreasing Ar-cluster size, which might be an approach to converge the different sputter rates.