Molecular profiling of single cells has the potential to significantly advance our understanding of cell function and cellular processes of importance to health and disease. In particular, small molecules with rapid turn-over rates can reveal activated metabolic pathways resulting from an altered chemical environment or cellular events such as differentiation. Consequently, techniques for quantitative metabolite detection acquired in a higher throughput manner are needed to characterize the biological variability between seemingly homogenous cells. Here, we show that nanospray desorption electrospray ionization (nano-DESI) mass spectrometry (MS) enables sensitive molecular profiling and quantification of endogenous species in single cells in a higher throughput manner. Specifically, we show a large number of detected amino acids and phospholipids, including plasmalogens, readily detected from single cheek cells. Further, by incorporating a phosphatidylcholine (PC) internal standard into the nano-DESI solvent, we determined the total amount of PC in one cell to be 1.2 pmoles. Finally, we describe a higher throughput approach where molecules in single cells are automatically profiled. These developments in single cell analysis provide a basis for future studies to understand cellular processes related to drug effects, cell differentiation and altered chemical microenvironments.

中文翻译：

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使用纳米DESI MS对单个细胞中的内源性分子进行分析和定量

单细胞的分子谱分析有可能极大地增进我们对细胞功能和对健康和疾病至关重要的细胞过程的理解。特别是，具有快速周转率的小分子可以揭示由化学环境变化或细胞事件（例如分化）导致的代谢途径活化。因此，需要以更高通量方式获得的定量代谢物检测技术来表征看似均质的细胞之间的生物学变异性。在这里，我们显示纳米喷雾解吸电喷雾电离（nano-DESI）质谱（MS）能够以更高的通量方式对单个细胞中的内源性物种进行敏感的分子分析和定量。具体来说，我们显示出大量检测到的氨基酸和磷脂，包括缩醛磷脂，很容易从单颊细胞中检测到。此外，通过将磷脂酰胆碱（PC）内标结合到纳米DESI溶剂中，我们确定一个单元中PC的总量为1.2 pmoles。最后，我们描述了一种更高通量的方法，该方法可以自动分析单个细胞中的分子。单细胞分析的这些进展为将来的研究奠定了基础，以了解与药物作用，细胞分化和化学微环境改变有关的细胞过程。我们描述了一种更高通量的方法，该方法可以自动分析单个细胞中的分子。单细胞分析的这些进展为将来的研究奠定了基础，以了解与药物作用，细胞分化和化学微环境改变有关的细胞过程。我们描述了一种更高通量的方法，该方法可以自动分析单个细胞中的分子。单细胞分析的这些进展为将来的研究奠定了基础，以了解与药物作用，细胞分化和化学微环境改变有关的细胞过程。