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Intact living-cell electrolaunching ionization mass spectrometry for single-cell metabolomics
Chemical Science ( IF 7.6 ) Pub Date : 2022-06-17 , DOI: 10.1039/d2sc02569h
Yunlong Shao 1 , Yingyan Zhou 1 , Yuanxing Liu 1 , Wenmei Zhang 1 , Guizhen Zhu 1 , Yaoyao Zhao 1 , Qi Zhang 1 , Huan Yao 2 , Hansen Zhao 2 , Guangsheng Guo 1, 3 , Sichun Zhang 2 , Xinrong Zhang 2 , Xiayan Wang 1
Affiliation  

While single-cell mass spectrometry can reveal cellular heterogeneity and the molecular mechanisms of intracellular biochemical reactions, its application is limited by the insufficient detection sensitivity resulting from matrix interference and sample dilution. Herein, we propose an intact living-cell electrolaunching ionization mass spectrometry (ILCEI-MS) method. A capillary emitter with a narrow-bore, constant-inner-diameter ensures that the entire living cell enters the MS ion-transfer tube. Inlet ionization improves sample utilization, and no solvent is required, preventing sample dilution and matrix interference. Based on these features, the detection sensitivity is greatly improved, and the average signal-to-noise (S/N) ratio is about 20 : 1 of single-cell peaks in the TIC of ILCEI-MS. A high detection throughput of 51 cells per min was achieved by ILCEI-MS for the single-cell metabolic profiling of multiple cell lines, and 368 cellular metabolites were identified. Further, more than 4000 primary single cells digested from the fresh multi-organ tissues of mice were detected by ILCEI-MS, demonstrating its applicability and reliability.

中文翻译:


用于单细胞代谢组学的完整活细胞电发射电离质谱法



虽然单细胞质谱可以揭示细胞异质性和细胞内生化反应的分子机制,但其应用受到基质干扰和样品稀释导致的检测灵敏度不足的限制。在此,我们提出了一种完整的活细胞电发射电离质谱(ILCEI-MS)方法。具有窄孔、恒定内径的毛细管发射器可确保整个活细胞进入 MS 离子传输管。入口电离提高了样品利用率,并且不需要溶剂,防止样品稀释和基质干扰。基于这些特点,检测灵敏度大大提高,ILCEI-MS TIC中单细胞峰的平均信噪比(S/N)约为20:1。 ILCEI-MS 对多个细胞系的单细胞代谢分析实现了每分钟 51 个细胞的高检测通量,并鉴定了 368 种细胞代谢物。此外,ILCEI-MS对小鼠新鲜多器官组织消化的4000多个原代单细胞进行了检测,证明了其适用性和可靠性。
更新日期:2022-06-17
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