During the project, we have set up the new analytical methodologies which form the basis of the SUMMIT project, and we explored some groundbreaking applications
On the methodological side, the main achievements include:
• The fine optimization of our prototype dissolution-DNP experimental setting for the robust and reproducible analysis of complex metabolic mixtures;
• The development of novel ultrafast 2D NMR experiments for the rapid screening of complex chemical samples (which turned out to be useful for other applications such as reaction monitoring);
• The development of a new NMR detection approach for hyperpolarized experiment, consisting in recording 1H and 13C spectra of a single hyperpolarized sample within the same experiment;
• The comprehensive description of concepts underlying ultrafast 2D NMR for analytical chemistry applications;
• The development of dedicated processing tools to extract relevant data from 2D spectra of complex mixtures.
On the application side, we have demonstrated for the first time that dissolution-DNP can provide relevant information in a full metabolomics study based on 13C NMR at natural isotopic abundance. First, we demonstrated that our approach could extract biologically relevant information on plant metabolism by analyzing tomato fruit extracts at different development stages. Then, thanks to a careful optimization of experimental parameters, we demonstrated that 13C spectra of urine at natural abundance could be recorded in a single scan with a sensitivity equivalent to that of a 1H NMR experiment, with an analytical performance that made it possible to quantify metabolites that could not be measured with conventional NMR. In the last part of the project, we collaborated with clinicians in Nantes to perform the first clinical metabolomics study involving hyperpolarized NMR metabolomics. We demonstrated that hyperpolarized 13C at natural abundance provided complementary information compared to conventional NMR, leading to the detection of two biomarkers that were not detected by conventional 1H NMR metabolomics. This final result, which is beyond the expectations of the SUMMIT project, opens many application perspectives. It paves the way to many different applications which will be explored in the near future, through the MetaboHub national research infrastructure cand through various funded projects.
In addition to these scientific advances, we organized two international symposiums, one on hyperpolarized NMR for the analysis of mixtures (in 2022), and another one on NMR metabolomics (in 2025). These events were a unique opportunity to present the project results to a broad audience of top international experts, to update the team on the latest advances in the field, to discuss potential collaborations, and for students to network and discuss career opportunities.
In conclusion, the results of the SUMMIT project should have a broad impact for the many applications that require for the analysis of complex samples by NMR spectroscopy, in particular metabolomics. It provides new analytical tools for a broad community of researchers in chemistry and biology.
