Droplet-Splitting Microchip Online Coupled with Time-Resolved ICPMS for Analysis of Released Fe and Pt in Single Cells Treated with FePt Nanoparticles.

The intracellular release of Fe/Pt ions from FePt nanoparticles (NPs) in single cells is highly critical to elucidate the potential cytotoxicity or potential cell protection mechanism of FePt NPs. For the first time, the quantitative analysis of Fe/Pt released from FePt-Cys NPs in single cells was achieved by a droplet-splitting microchip coupled online to inductively coupled plasma mass spectrometry detection. The droplet-splitting chip integrates droplet generation, cell lysis, and droplet-splitting units. The quantification of released Fe/Pt was achieved via measuring standard Fe/Pt ionic solutions. For the determination of total Fe/Pt in single cells, the same microchip with different operation modes (total-mode) was used, and the quantification of total Fe/Pt was achieved with FePt NPs as the standard. The developed method with two analysis modes was applied to study the decomposition behavior of FePt-Cys NPs in single cells, and the results indicated that the percentages of the cells absorbing/decomposing FePt-Cys NPs increased with the incubation time. Almost all cells absorbed FePt-Cys NPs after 6 h, while only about 60% cells decomposed FePt-Cys NPs after 6 h and almost all cells decomposed FePt-Cys NPs after 18 h. Besides, the released Fe content was lower than its endogenous content in cells and the release rate of Pt was higher than that of Fe, providing a possibility that the released Pt may contribute more to cytotoxicity. The developed system enabled fractionation of Fe/Pt in single cells treated with FePt NPs with high accuracy, easy operation, and high throughput and showed a great potential for elemental speciation at the single-cell level.