Leonidas Mavroudakis: Analytical developments and applications of ambient mass spectrometry imaging: Visualizing challenging analytes and understanding chemical mechanisms of ischemic stroke

  • Datum: 3 november 2023, kl. 9.15
  • Plats: Room B42, BMC, Husargatan 3, Uppsala
  • Typ: Disputation
  • Respondent: Leonidas Mavroudakis
  • Opponent: Malcolm Clench
  • Handledare: Ingela Lanekoff, Daniel Globisch
  • Forskningsämne: Kemi med inriktning mot analytisk kemi
  • DiVA

Abstract

Bioanalytical methods that provide spatial information on molecular distributions are important for deep understanding of chemical mechanisms in health and disease. For instance, the localized action of drugs and metabolites can provide valuable information on metabolism in specific cellular regions, which would not be possible with bulk analysis. Mass spectrometry imaging (MSI) is a powerful tool for realizing molecular distributions directly from the surface of biological samples e.g., tissue sections. Analytical and technological developments over the past years have constituted MSI as a valuable asset in the bioanalysis toolbox. 

Several MSI techniques exist for transferring the analytes from the tissue surface to the mass spectrometer. In this thesis, pneumatically assisted (PA) nanospray desorption electrospray ionization (nano-DESI) was used for ambient MSI of thin tissue sections. In PA nano-DESI MSI, molecules from the surface of the tissue section are desorbed into a liquid stream of solvent that is formed between two thin fused silica capillaries and electrosprayed directly into the mass spectrometer. The extraction solvent allows for addition of internal standards for matrix effects compensation and relative quantitation, and dopants for improved ionization efficiency of analytes as well as host-guest chemistry.

In this work, PA nano-DESI MSI was evaluated for its ability to provide insights into chemical mechanisms in health and disease. The effect of preconditioning agents on the membrane lipid breakdown after stroke as well as the effect of ischemia on acylcarnitine metabolism, which is involved in oxidation of fatty acids, was studied. These results provided valuable information into the chemical mechanisms that are induced during ischemia. Additionally, analytical insights are provided on the extraction abilities of various solvents used in PA nano-DESI. Further, analytical methodologies have been developed for analyzing challenging analytes, particularly light alkali metal ions (Na+ and K+), which cannot be directly detected by modern high resolution mass spectrometers, and prostaglandins, which exhibit many isomers that are not distinguishable through mass spectrometry alone. Finally, PA nano-DESI MSI was combined in one analytical platform with surface sampling capillary electrophoresis mass spectrometry (SS-CE-MS) to increase the coverage of information obtained from a single tissue section, i.e. elucidating isomeric species through electrophoretic separation.

Overall, this thesis adds unique insights into understanding ischemic stroke and presents novel analytical methodologies for analyzing prostaglandins, and Na+ and K+ ions. All developed methods are fully compatible with liquid extraction based MSI techniques which expands the range of applications.

FÖLJ UPPSALA UNIVERSITET PÅ

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