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Correlative Optical Spectroscopy and Mass Spectrometry Imaging Methodology to Visualise Drug Distribution in a Soft Tissue Section
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Multimodal mass spectrometry - Raman imaging reveals solvent dependent structural and chemical tissue alterations.
Gabor Toth1, Adrianna Kryska2, Anna Sroka-Bartnicka2
1Department of Chemistry - BMC, Uppsala University, Husargatan 3, 75237, Uppsala, Sweden; Center of Excellence for the Chemical Mechanisms of Life, Uppsala University, Sweden.
Analytica Chimica Acta
|August 18, 2025
Summary
Combining mass spectrometry imaging (MSI) and Raman spectroscopy reveals solvent-induced chemical changes in tissues. This multimodal approach enhances chemical analysis and uncovers previously unknown tissue alterations after imaging.
Area of Science:
- Chemical imaging
- Multimodal analysis
- Tissue characterization
Background:
- Mass spectrometry imaging (MSI) and Raman spectroscopy are complementary chemical imaging techniques for analyzing thin tissue sections.
- MSI detects mass-to-charge ratios, while Raman spectroscopy detects molecular vibrations, offering distinct chemical information.
- MSI can be destructive, whereas Raman spectroscopy is less invasive, making their combination advantageous.
Purpose of the Study:
- To establish and demonstrate a multimodal workflow integrating pneumatically assisted nanospray desorption electrospray ionization (PA nano-DESI) MSI and Raman spectroscopy on the same tissue section.
- To investigate solvent-induced chemical alterations in tissue resulting from PA nano-DESI MSI.
- To uncover previously unknown chemical changes in tissue after MSI analysis.
Main Methods:
- Integration of PA nano-DESI MSI with Raman spectroscopy on identical tissue locations.
- Adaptation of MSI protocols to accommodate Raman spectroscopy sample requirements.
- Systematic analysis of chemical alterations caused by different solvents (methanol, acetonitrile) and sampling parameters.
Main Results:
- Successful integration of MSI and Raman spectroscopy for comprehensive tissue chemistry characterization.
- Raman spectroscopy effectively identified solvent-induced chemical alterations, including protein denaturation.
- Methanol was found to desorb more material than acetonitrile, with both solvents causing significant tissue changes.
Conclusions:
- A robust multimodal workflow combining PA nano-DESI MSI and Raman spectroscopy was established for analyzing the same tissue sections.
- This integrated approach revealed novel insights into solvent-tissue interactions and MSI-induced chemical modifications.
- The findings highlight the potential of combining MSI and Raman spectroscopy for in-depth chemical characterization of biological tissues.

