Intact living-cell electrolaunching ionization mass spectrometry for single-cell metabolomics

Yunlong Shao; Yingyan Zhou; Yuanxing Liu; Wenmei Zhang; Guizhen Zhu; Yaoyao Zhao; Qi Zhang; Huan Yao; Hansen Zhao; Guangsheng Guo; Sichun Zhang; Xinrong Zhang; Xiayan Wang

doi:10.1039/D2SC02569H

Intact living-cell electrolaunching ionization mass spectrometry for single-cell metabolomics†

Yunlong Shao,^a Yingyan Zhou,^a Yuanxing Liu,^a Wenmei Zhang,^a Guizhen Zhu,^a Yaoyao Zhao,*^a Qi Zhang,^a Huan Yao,^b Hansen Zhao,^b Guangsheng Guo,^ac Sichun Zhang,

^b Xinrong Zhang

^b and Xiayan Wang

*^a

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* Corresponding authors

^a Department of Chemistry and Biology, Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Beijing University of Technology, Beijing 100124, P. R. China
E-mail: zhaoyaoyao@bjut.edu.cn, xiayanwang@bjut.edu.cn

^b Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China

^c Minzu University of China, Beijing 100081, P. R. China

Abstract

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.

Chemical Science

Intact living-cell electrolaunching ionization mass spectrometry for single-cell metabolomics†

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Intact living-cell electrolaunching ionization mass spectrometry for single-cell metabolomics

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