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.
Highlights
Polycystic kidney disease (PKD) is a complex clinical entity unifying a group of diseases that results in renal cyst development[1]
With this report we demonstrate the utility of CESI-MS for metabolic profiling of biomass-restricted tissue material and, at the same time, we provide a descriptive study of the metabolic changes associated with polycystic kidney disease (PKD) progression[1]
We present a first application of sheathless Capillary electrophoresis-mass spectrometry (CE-MS) (CESI-MS) for metabolic profiling of biomass-restricted tissue samples, namely individual sections of mouse kidney
Summary
Polycystic kidney disease (PKD) is a complex clinical entity unifying a group of diseases that results in renal cyst development[1]. The porous tip interface (offered by SCIEX as CESI sprayer) can substantially improve the detection sensitivity (i.e., up to 100-fold) as compared to using a conventional co-axial sheath-liquid interface[7,8]. Another advantage of the porous tip sprayer interface is reduced ion suppression, which is inherent to the use of flow rates below 20 nL/min in ESI-MS9. With this report we demonstrate the utility of CESI-MS for metabolic profiling of biomass-restricted tissue material and, at the same time, we provide a descriptive study of the metabolic changes associated with PKD progression[1]
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