Concentric Hybrid Nanoelectrospray Ionization‐Atmospheric Pressure Chemical Ionization Source for High‐Coverage Mass Spectrometry Analysis of Single‐Cell Metabolomics

Autor: Tianrun Xu, Hang Li, Peng Dou, Yuanyuan Luo, Siming Pu, Hua Mu, Zhihao Zhang, Disheng Feng, Xuesen Hu, Ting Wang, Guang Tan, Chuang Chen, Haiyang Li, Xianzhe Shi, Chunxiu Hu, Guowang Xu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Advanced Science, Vol 11, Iss 16, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202306659
Popis: Abstract High‐coverage mass spectrometry analysis of single‐cell metabolomics remains challenging due to the extremely low abundance and wide polarity of metabolites and ultra‐small volume in single cells. Herein, a novel concentric hybrid ionization source, nanoelectrospray ionization‐atmospheric pressure chemical ionization (nanoESI‐APCI), is ingeniously designed to detect polar and nonpolar metabolites simultaneously in single cells. The source is constructed by inserting a pulled glass capillary coaxially into a glass tube that acts as a dielectric barrier layer. Benefitting from the integrated advantages of nanoESI and APCI, its limit of detection is improved by one order of magnitude to 10 pg mL−1. After the operational parameter optimization, 254 metabolites detected in nanoESI‐APCI are tentatively identified from a single cell, and 82 more than those in nanoESI. The developed nanoESI‐APCI is successively applied to study the metabolic heterogeneity of human hepatocellular carcinoma tissue microenvironment united with laser capture microdissection (LCM), the discrimination of cancer cell types and subtypes, the metabolic perturbations to glucose starvation in MCF7 cells and the metabolic regulation of cancer stem cells. These results demonstrated that the nanoESI‐APCI not only opens a new avenue for high‐coverage and high‐sensitivity metabolomics analysis of single cell, but also facilitates spatially resolved metabolomics study coupled with LCM.
Databáze: Directory of Open Access Journals
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