Analytical chemistry: a new ultra-sensitive approach to metabolomics

Scientists from the CEISAM laboratory (Chemistry and Interdisciplinarity: Synthesis, Analysis, Modeling – Nantes University – CNRS) have developed a new approach for detecting metabolic biomarkers of clinical pathologies using nuclear magnetic resonance (NMR). This breakthrough in analytical chemistry, which opens up many new prospects for biomedical studies, has just been published in the Journal of the American Chemical Society.

Metabolomics aims to detect and quantify the small molecules (metabolites) involved in the functioning of living organisms. This approach relies on cutting-edge analytical methods such as nuclear magnetic resonance (NMR) spectroscopy, an exceptionally precise analytical tool capable of detecting and quantifying dozens or even hundreds of different small molecules present in samples of biological interest, such as biofluids like blood or urine. Metabolomics can thus highlight metabolic pathways or reveal biomarkers characteristic of a given pathology.

However, metabolomics faces a major challenge: the extreme complexity of the biological samples studied. This often requires the analytical methods at the heart of this approach to make compromises between sensitivity (the ability to detect low-concentration molecules) and resolution (the ability to separate signals from mixed molecules, and thus identify the molecules in question). These constraints are a limitation for metabolomics applications, particularly in the clinical field.

A new NMR method offering unrivalled resolution and sensitivity

The analytical chemistry team at the Chimie et Interdisciplinarité : Synthèse, Analyse, Modélisation laboratory (Chemistry and Interdisciplinarity: Synthesis, Analysis, Modeling – Nantes University – CNRS) has recently developed an approach offering unrivalled resolution and sensitivity for NMR metabolomics. The method is based on dynamic nuclear polarization, which makes it possible to obtain spectral signatures of biological samples using carbon-13 NMR spectroscopy, despite the low natural abundance of this nucleus.

For the first time, this approach has been applied to urine samples from patients suffering from chronic kidney disease, as part of a collaboration between CEISAM and the Thorax Institute, also involving researchers from the University of Geneva and equipment manufacturer Bruker. The researchers demonstrated that this new approach can reveal biomarkers associated with this pathology, including some that were not detected by conventional metabolomic NMR approaches.

Ces résultats, récemment publiés dans le Journal of the American Chemical Society, ouvrent de nombreuses perspectives à l’interface entre chimie analytique et santé. Ils constituent un résultat majeur du projet ERC SUMMIT, porté par le professeur Patrick Giraudeau.

Photo credit: CEISAM and Institut du thorax – Wilfried Antoine Desveaux

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