Sheathless CE-MS based metabolic profiling of kidney tissue section samples from a mouse model of Polycystic Kidney Disease

基于无鞘 CE-MS 对多囊肾病小鼠模型的肾脏组织切片样本进行代谢分析

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作者:Elena Sánchez-López, Guinevere S M Kammeijer, Antonio L Crego, María Luisa Marina, Rawi Ramautar, Dorien J M Peters, Oleg A Mayboroda

Abstract

Capillary electrophoresis-mass spectrometry (CE-MS) using a sheathless porous tip interface emerged as an attractive tool in metabolomics thanks to its numerous advantages. One of the main advantages compared to the classical co-axial sheath liquid interface is the increased sensitivity, while maintaining the inherent properties of CE, such as a high separation efficiency and low sample consumption. Specially, the ability to perform nanoliter-based injections from only a few microliters of material in the sample vial makes sheathless CE-MS a well-suited and unique approach for highly sensitive metabolic profiling of limited sample amounts. Therefore, in this work, we demonstrate the utility of sheathless CE-MS for metabolic profiling of biomass-restricted samples, namely for 20 µm-thick tissue sections of kidney from a mouse model of polycystic kidney disease (PKD). The extraction method was designed in such a way to keep a minimum sample-volume in the injection vial, thereby still allowing multiple nanoliter injections for repeatability studies. The developed strategy enabled to differentiate between different stages of PKD and as well changes in a variety of different metabolites could be annotated over experimental groups. These metabolites include carnitine, glutamine, creatine, betaine and creatinine. Overall, this study shows the utility of sheathless CE-MS for biomass-limited metabolomics studies.

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