Single-Cell Isotope Dilution Analysis with LA–ICP–MS: A New Approach for Quantification of Nanoparticles in Single Cells

Abstract

Laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP–MS) is an emerging method for the analysis of metal nanoparticles (NPs) in single cells. However, two main obstacles, low analytical throughput and lack of commercial reference materials, need to be overcome. In this work, we demonstrated the principles of a new approach termed “single-cell isotope dilution analysis” (SCIDA) to remove the two obstacles. For a proof of concept, macrophage cells were chosen as a model to study the uptake of silver NPs (AgNPs) at a single-cell level. Single cells exposed to AgNPs were placed in an array by a microfluidic technique; each cell in the array was precisely dispensed with a known picoliter droplet of an enriched isotope solution with a commercial inkjet printer; accurate quantification of AgNPs in single cells was done by using isotope dilution LA–ICP–MS. The average Ag mass of 1100 single cells, 396 ± 219 fg Ag per cell, was in good accord with the average of the population of cells determined by solution ICP–MS analysis. The detection limit was 0.2 fg Ag per cell. The SCIDA approach is expected to be widely applied for the study of cell–NP interactions and biological effects of NPs at the single-cell level.

PLGA-Gold Nanocomposite: Preparation and Biomedical Applications

“…In another recent report, single-cell isotope dilution analysis using laser ablation ICP-MS was used to quantify the content of silver nanoparticles inside a single microphage. The reported approach resulted in a limit of detection inside a single cell as low as 0.2 fg Ag per cell [ 39 ]. Focused reviews on the applications of ICP-MS for metal-based nanoparticles uptake by cells are available elsewhere [ 40 , 41 , 42 ].…”

Analytical Methodologies for Agrometallomics: A Critical Review

“…213 So, ID-LA-ICP-MS is suitable for in situ quantitative imaging of trace elements in biological samples, such as animals, 214 plants, 215 protein, and even single cell. 216 5.2. Electrothermal Vaporization Hyphenation Technique.…”

“…274 However, the main challenge of single cell LA-ICP-MS analysis is still the precise quantification in complicated matrixes. 190 For this, Zheng et al 216 performed single-cell isotope dilution analysis (SCIDA) by dropping an isotope solution in a single cell with an inkjet printer, of which AgNPs quantification in a single cell was favorably fulfilled by isotope dilution LA-ICP-MS.…”

Metallomics in Multidisciplinary Research and the Analytical Advances

“…Wang et al 42 quantified gold nanoparticles in single cells with time-resolved ICP-MS, a process which can be regarded as single-cell metallomics. 43 Single-cell-based mass cytometry represents a breakthrough technique for the biomedical sciences and precision medicine. Furthermore, the study of the spatial distribution (the 2D, 3D, and even 4D) of metallomes is called spatial metallomics, and this has been applied in nanotoxicological research.…”