Research topics

The mass spectrometry team’s research topics are in the field of structural gas phase chemistry with a triple perspective: fundamental aspects, methodology and applications (chemistry/biology).

All the projects are fully in line with an interdisciplinary approach in material sciences and engineering for life. The aim is to propose new analytical chemistry tools, make them available to the entire community by distributing them through academic or industrial partners, and interact strongly with specialists in biology, medicine, cosmetics or ecology for a better understanding of living organisms.


  • MALDI-TOF/TOF UltrafleXtreme (Bruker Daltonics)
  • Q-ToF 6540 (Agilent Technologies)
  • Liquid chromatographic system 1260Prime et de supercritical fluid chromatography (SFC) 1260SFC (Agilent Technologies)
  • GC-MS (Agilent Technologies)

Manager: David Touboul

Fundamental Aspects

Mass spectrometry must be considered as a science in its own requiring work of a fundamental nature in order to better understand ionization and fragmentation processes. In this context, three questions are being asked in the laboratory:

  • Determination of the internal energy of ions produced during desorption/ionization or electrospray processes: Chemical thermometers (benzylpyridinium salts) are used to evaluate the parameters influencing the internal energy of the ions produced by SIMS and ESI after SFC coupling.

    Fu T, Della-Negra S, Touboul D, Brunelle A. J Am Soc Mass Spectrom. 2019;30(2):321-328.

  • Determination of the physico-chemical properties of fluids entering a mass spectrometer: This involves a better understanding of the changes in the state of matter during SFC-MS coupling, particularly in the relaxation zone of supercritical CO2.
  • Propriétés physico-chimiques des différents états de la matière

    Physico-chemical properties of the different states of matter

    Diagramme de phase du CO2

    CO2 phase diagram

  • Determination of new biomolecule fragmentation mechanisms: This involves exploring new fragmentation pathways, in particular radical pathways induced by a change in the redox state of a metal cation after activation by gas phase collision.
    Fragmentation radicalaire induite par le changement de degré d’oxydation du Cu2+ après activation collisionnelle

    Radical fragmentation induced by the change in the oxidation degree of Cu2+ after collisional activation

Methodology in Structural Chemistry

  • Supercritical fluid chromatography coupled with high-resolution tandem mass spectrometry (SFC-HRMS/MS): SFC offers complementary performances to traditional LC techniques in terms of selectivity, analytical speed and injection capacity of organic solvents (hexane, chloroform, DMSO…). We carry out methodological developments requiring the optimization of the SFC coupling with HRMS/MS detection methods, in particular the use of APPI (Atmospheric Pressure PhotoIonization) type sources and post-column metal cationization.
    Analyse SFC-APPI-MS de dérivés de vitamine E (tocophérols et tocotriènols), Méjean M, Brunelle A, Touboul D. Anal Bioanal Chem. 2015; 407(17):5133-42

    SFC-APPI-MS analysis of vitamin E derivatives (tocopherols and tocotrienols), Méjean M, Brunelle A, Touboul D. Anal Bioanal Chem. 2015; 407(17):5133-42

  • Big data analysis/molecular network: Modern data acquisition techniques in MS/MS mass spectrometry (DDA and DIA) have led to the increasing difficulty of processing these data in a non-automated way. In this context, our team is developing new tools based on molecular networks. The classical approach described on the historical GNPS platform has been improved by using the t-SNE (t-distributed stochastic neighbor embedding) algorithm to organize the data set. For further information, please refer to the dedicated website:
  • Functionalized surfaces (Nanostructure-Initiator Mass Spectrometry, NIMS): This project is being carried out in collaboration with Alain Paris (MNHN) and Pr. Chen (ENS Paris) and aims to develop new functionalized surfaces of the NIMS type for the detection of primary and secondary metabolites by desorption/ionization LASER without matrix deposition. The first experiments allowed us to validate the manufacture of surfaces by following the reference work in the field (Nature. 2007 Oct 25;449(7165):1033-6) and to perform the first NIMS images in the laboratory.

Chemistry of the living and for the living

  • Mass Spectrometry Imaging: Our team has been conducting research and application work in the field of MALDI and TOF-SIMS mass spectrometry imaging for over 15 years. This activity has led to the publication of more than 50 articles in the field and has placed us as one of the world leaders in this field. Following Alain Brunelle’s departure for the LAMS laboratory with the TOF-SIMS instrument, we have chosen to focus our methodological developments in MALDI imaging (NIMS, or even Methodology in Structural Chemistry) and applications in the field of natural products, in particular the distribution of secondary metabolites from microorganisms.

    Vallet et al., J Nat Prod. 2017; 80(11):2863-2873

  • Chemical ecology: The work carried out in mass spectrometry imaging has led us to become involved in chemical ecology projects in order to better understand inter-organism relations (quorum sensing/quenching and microorganisms associated with termites in French Guiana) in collaboration with the V. Eparvier team and the Laboratory of Biodiversity and Microbial Biotechnologies (LBBM – USR 3579, Banuyls). The aim is to develop new methods for identifying and quantifying molecules involved in quorum sensing/quenching and protecting pathogens by microorganisms associated with termites using SFE-SFC-HRMS/MS approaches.
    Séparation SFC-HRMS de N-acyl homosérine-L-lactones (HSLs)

    SFC-HRMS separation of N-acyl homoserine-L-lactones (HSLs)

  • Lipidomics: Lipidomics, as a sub-domain of metabolomics, has gained importance over the past decade through the development of sensitive and specific methods in mass spectrometry. In this context, we have focused on the development of targeted methods (derived from vitamin A, vitamin E, environmental toxins (acetogenins)…) or global methods in SFC-HRMS. SFC allows the injection of complex mixtures in organic solvents and the efficient separation of position or stereo isomers into complex matrices. These methods are available to our academic colleagues (J. Jouhet, Université Grenoble Alpes) or industrial colleagues and are currently being developed through partnerships with companies in the field of cosmetics (Clarins, Ales Groupe, Gattefosse…).
    Profilage global de mélanges de lipides complexes par SFC-HRMS

    Global profiling of complex lipid mixtures by SFC-HRMS

  • Epigenetics: Due to its sensitivity and specificity, mass spectrometry is a particularly effective tool for identifying, detecting and quantifying chemical changes in DNA and RNA. In this context, we have developed approaches based on the purification of oligonucleotides by our biological collaborators followed by MALDI-TOF/TOF mass spectrometric analyses. This allows us to perform the exact mass measurement of modified and unmodified oligonucleotides and to determine the position of these modifications after partial enzymatic digestion. Studies of RNA methylation kinetics have been undertaken to better understand the regulatory processes for these changes. Finally, we have set up a workflow allowing the absolute quantification of canonical or modified nucleosides from RNA or DNA extracts.
    Spectres MALDI-MS/MS d’oligonucléotides méthylés. Guelorget A, Roovers M, Guérineau V, Barbey C, Li X, Golinelli-Pimpaneau B. Nucleic Acids Res. 2010; 38(18):6206-18.

    MALDI-MS/MS spectra of methylated oligonucleotides. Guelorget A, Roovers M, Guérineau V, Barbey C, Li X, Golinelli-Pimpaneau B. Nucleic Acids Res. 2010; 38(18):6206-18.