Nanocapillary sampling coupled to liquid chromatography mass spectrometry delivers single cell drug measurement and lipid fingerprints.
Nanocapillary sampling coupled to liquid chromatography mass spectrometry delivers single cell drug measurement and lipid fingerprints.
复制标题
纳米毛细管采样与液-质联用提供单细胞药物测量和脂类指纹图谱。
DOI：
10.1039/d2an01732f
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发表时间：
2023-02-27
期刊：
影响因子：
4.2
通讯作者：
Bailey, Melanie J.
中科院分区：
文献类型：
--
作者：
Lewis, Holly-May;Gupta, Priyanka;Saunders, Kyle D. G.;Briones, Shazneil;von Gerichten, Johanna;Townsend, Paul A.;Velliou, Eirini;Beste, Dany J. V.;Cexus, Olivier;Webb, Roger;Bailey, Melanie J.
这项工作描述了一种新的方法来测量单个活哺乳动物细胞中的药物水平和脂质指纹的发展。纳米毛细管取样是一种能够在显微镜观察下选择和分离单个活细胞的方法。在这里，活的单细胞纳米毛细管采样耦合到液相色谱的第一次。这允许在电离之前分离分子种类，并提高药物分析物的测量精度。在这项工作中，将分析物从取样毛细管转移到小瓶中的效率被优化。该分析是使用标准流动液相色谱法与广泛使用的质谱仪器相结合进行的，突出了广泛采用的机会。该方法应用于30个活细胞，揭示了不同药物分子摄取的细胞间异质性。使用该系统，我们检测到每个单细胞14-158个脂质特征，揭示了贝达喹啉摄取与脂质指纹之间的关联。这项工作描述了一种新的方法来测量单个活细胞中的药物水平和脂质指纹的发展。
This work describes the development of a new approach to measure drug levels and lipid fingerprints in single living mammalian cells. Nanocapillary sampling is an approach that enables the selection and isolation of single living cells under microscope observation. Here, live single cell nanocapillary sampling is coupled to liquid chromatography for the first time. This allows molecular species to be separated prior to ionisation and improves measurement precision of drug analytes. The efficiency of transferring analytes from the sampling capillary into a vial was optimised in this work. The analysis was carried out using standard flow liquid chromatography coupled to widely available mass spectrometry instrumentation, highlighting opportunities for widespread adoption. The method was applied to 30 living cells, revealing cell-to-cell heterogeneity in the uptake of different drug molecules. Using this system, we detected 14–158 lipid features per single cell, revealing the association between bedaquiline uptake and lipid fingerprints. This work describes the development of a new approach to measure drug levels and lipid fingerprints in single living cells.
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