ToF-SIMS is a label-free imaging method that has been shown to enable imaging of amiodarone in single rat macrophage (NR8383) cells. In this study, we show that the method extends to three other cell lines relevant to drug discovery: human embryonic kidney (HEK293), cervical cancer (HeLa), and liver cancer (HepG2). There is significant interest in the variation of drug uptake at the single cell level, and we use ToF-SIMS to show that there is great diversity between individual cells and when comparing each of the cell types. These single cell measurements are compared to quantitative measurements of cell-associated amiodarone for the population using LC/MS/MS and cell counting with flow cytometry. NR8383 and HepG2 cells uptake the greatest amount of amiodarone with an average of 2.38 and 2.60 pg per cell, respectively, and HeLa and Hek 293 have a significantly lower amount of amiodarone at 0.43 and 0.36 pg per cell, respectively. The amount of cell-associated drug for the ensemble population measurement (LC/MS/MS) is compared with the ToF-SIMS single cell data: a similar amount of drug was detected per cell for the NR8383, and HepG2 cells at a greater level than that for the HEK293 cells. However, the two techniques did not agree for the HeLa cells, and we postulate potential reasons for this.

中文翻译：

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细胞内药物吸收-使用ToF-SIMS成像进行单细胞测量的比较以及使用LC / MS / MS从细胞群体中定量

ToF-SIMS是一种无标记的成像方法，已被证明可以对单个大鼠巨噬细胞（NR8383）细胞中的胺碘酮进行成像。在这项研究中，我们表明该方法扩展到其他三个与药物发现相关的细胞系：人胚肾（HEK293），宫颈癌（HeLa）和肝癌（HepG2）。人们对单细胞水平上药物吸收的变化非常感兴趣，我们使用ToF-SIMS来显示各个细胞之间以及比较每种细胞类型时存在很大的多样性。使用LC / MS / MS将这些单细胞测量结果与该人群的细胞相关胺碘酮的定量测量结果进行比较，并通过流式细胞术对细胞进行计数。NR8383和HepG2细胞摄取的胺碘酮数量最多，平均每个细胞分别为2.38 pg和2.60 pg，HeLa和Hek 293的胺碘酮含量分别低得多，分别为0.43和0.36 pg /细胞。将用于集合人口测量（LC / MS / MS）的与细胞相关的药物数量与ToF-SIMS单细胞数据进行比较：对于NR8383，每个细胞检测到相似数量的药物，而更高水平的HepG2细胞而不是HEK293细胞。但是，这两种技术在HeLa细胞上并不一致，因此我们推测了可能的原因。