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Theme 1 colloquium: “Analytical ion spectroscopy: a new route to biomarker discovery in metabolomics“ (Lecture)

Tuesday 5 June 2018Add to my calendar
from 16:00
dr. Jonathan Martens (Molecular Structure and Dynamics)

Jonathan MartensLimitations in common experimental techniques for small molecule identification that are ultra-sensitive and selective, yet remain generally applicable, are a common bottleneck encountered in many areas of (bio)analytical science. Infrared ion spectroscopy (IR-IS) has developed over the past decade as a powerful tool for identifying the molecular structures of compounds detected in mass spectrometry-based experiments. Using this approach, infrared vibrational spectra can be recorded for mass-isolated ions and provide a signature that can be used to accurately determine the details of a compound’s molecular structure. At FELIX, we have recently implemented IR-IS experiments in state-of-the-art analytical chromatography/mass spectrometry platforms, combining the full sensitivity of mass spectrometry for compound detection with an orthogonal characterization of molecular structure by IR-IS1-2.

In this talk I will highlight the strengths of this technique using several examples from the field of metabolomics3-4. Clinical metabolomics laboratories have a focus on the characterization of new metabolic diseases through the identification of small molecule biomarkers using metabolic screening of patients. This involves the analysis of common body fluids, such as blood plasma/serum, urine and cerebrospinal fluid (CSF) using liquid chromatography mass spectrometry (LC-MS) to detect metabolites that correlate with a particular disease. LC-MS is excellent at detecting, by mass, compounds in patient body fluids and in a routine analysis several thousand compounds can be detected in a single run. The downside of the technique is simply that based on mass information alone, approximately 80% of those compounds cannot be identified. In order to identify the detected compounds one must rely on searching for corresponding masses in databases of known human metabolites (so-called, known unknowns). Two common failures exist with this approach: 1) the many structural and stereoisomers that are present as metabolites in the same sample cannot be distinguished and led to ambiguous assignments, and 2) compounds that are not previously known as metabolites cannot be identified (the unknown unknowns). I will highlight how IR-IS can be used to overcome both of these challenges using a previously detected but unidentified biomarker of a metabolic disease known as antiquitin deficiency.


  1. Martens, J.; Berden, G.; Gebhardt, C. R.; Oomens, J., Infrared ion spectroscopy in a modified quadrupole ion trap mass spectrometer at the FELIX free electron laser laboratory. Rev. Sci. Instrum. 2016,87 (10), 103108.
  2. Martens, J.; Koppen, V.; Berden, G.; Cuyckens, F.; Oomens, J., Combined Liquid Chromatography-Infrared Ion Spectroscopy for Identification of Regioisomeric Drug Metabolites. Anal. Chem. 2017,89 (8), 4359-4362.
  3. Martens, J.; Berden, G.; van Outersterp, R. E.; Kluijtmans, L. A. J.; Engelke, U. F.; van Karnebeek, C. D. M.; Wevers, R. A.; Oomens, J., Molecular identification in metabolomics using infrared ion spectroscopy. Scientific Reports 2017,7 (1), 3363.
  4. Martens, J.; Berden, G.; Bentlage, H.; Coene, K. L. M.; Engelke, U. F.; Wishart, D.; van Scherpenzeel, M.; Kluijtmans, L. A. J.; Wevers, R. A.; Oomens, J., Unraveling the unknown areas of the human metabolome: the role of infrared ion spectroscopy. J. Inherited Metab. Dis. 2018.
dr. Joost Bakker/dr. Gilles de Wijs