Determination of the uptake of lanthanide doped-carbon dots by human cells using single cell ICP-ToF-MS†

As the application of engineered nanoparticles in medical fields grows, there is a rising demand for techniques capable of determining how they interact with biological entities, including cells. Single Cell Inductively Coupled Plasma Time-of-Flight Mass Spectrometry (sc-ICP-ToF-MS) has been shown potential to assess the mass of nanoparticle tags uptaken by individual cells. However, this approach suffers from challenges related to inconsistencies in transport efficiency (TE) determination and data processing protocols, which greatly impact the quality of the data. To address these issues, a novel metrological approach for the identification of cell events and determination of their TE is presented here for the first time. It is based on using the ratio of Eu to Yb signals in a single event to distinguish cellular events from background noise when analyzing HeLa cells tagged with lanthanide-doped carbon dots (Ln-CDs). To achieve this, Ln-CDs with Eu (4.3%) and Yb (3.4%) were synthesized, characterized and cytotoxicity assays were performed to confirm their biocompatibility. HeLa cells were exposed to these multielement Ln-CDs at varying concentrations to evaluate their cellular uptake. Laser ablation (LA)-ICP-MS analysis of individual isolated cells (n = 1578) confirmed cell tagging efficiency of 99.87%. Using this approach and CytoNeb–CytoSpray interface, TE values between 40–50% were achieved. The results showed a dosage dependent uptake of Ln-CDs by cells, with final concentrations ranging from 6.8 to 5115 fg Ln-CDs per cell.