Nanomaterials are increasingly being used in catalysis, optics and medicine, and their applications are expected to increase even more along the next decade. The development of multifunctional nanomaterials combining different properties to enable multimodal analysis has also become an attractive area of research. This multifunctional behaviour is typically achieved by doping the nanostructure with heteroatoms, transforming them into suitable nanotools for a wide range of biomedical applications.

On the other hand, current development and applications of nanomaterials have also raised health concerns as some of them are widely used in diagnosis and therapeutics. As a result, there is a need for analytical techniques/methods capable of determining how these nanoparticles interact with biological systems, down to the single cell level. Amongst all methodologies that study cells on a cell-to-cell basis, single-cell (sc) ICP-MS is the only approach that has been demonstrated to provide quantitative elemental data. In this sense, sc-ICP-ToF-MS allows the fast, multiple, and simultaneous study of different elements and isotopes within the same acquisition. However, sc-ICP-MS approaches suffer from challenges related to inconsistencies in transport efficiency (TE) determination and data processing protocols, which greatly impact the quality of the data.

To address such issues, we present a novel multimodal metrological approach for TE determination and elemental quantification using carbon-based nanoparticles (CDs) doped with Eu and Yb. This innovative platform relies on using the lanthanide ratio along with an improved data processing algorithm to distinguish cellular events from the background in sc-ICP-ToF-MS analysis of human cells.