A Multimodal Desorption Electrospray Ionisation Workflow Enabling Visualisation of Lipids and Biologically Relevant Elements in a Single Tissue Section

The colocation of elemental species with host biomolecules such as lipids and metabolites may shed new light on the dysregulation of metabolic pathways and how these affect disease pathogeneses. Alkali metals have been the subject of extensive research, are implicated in various neurodegenerative and infectious diseases and are known to disrupt lipid metabolism. Desorption electrospray ionisation (DESI) is a widely used approach for molecular imaging, but previous work has shown that DESI delocalises ions such as potassium (K) and chlorine (Cl), precluding the subsequent elemental analysis of the same section of tissue. The solvent typically used for the DESI electrospray is a combination of methanol and water. Here we show that a novel solvent system, (50:50 (%v/v) MeOH:EtOH) does not delocalise elemental species and thus enables elemental mapping to be performed on the same tissue section post-DESI. Benchmarking the MeOH:EtOH electrospray solvent against the widely used MeOH:H2O electrospray solvent revealed that the MeOH:EtOH solvent yielded increased signal-to-noise ratios for selected lipids. The developed multimodal imaging workflow was applied to a lung tissue section containing a tuberculosis granuloma, showcasing its applicability to elementally rich samples displaying defined structural information.

Automated summary

The co-localization of elemental species with host biomolecules allows for the understanding of metabolic dysregulation and disease pathogenesis. Alkali metals, widely studied and implicated in various diseases, disrupt lipid metabolism. Previous work in DESI molecular imaging has shown that the commonly used solvent system leads to ion delocalization, hindering subsequent elemental analysis. A novel solvent system (50:50 (%v/v) MeOH:EtOH) is presented here, which preserves the elemental species and enables post-DESI elemental mapping on the same tissue section. Benchmarking the MeOH:EtOH solvent against the commonly used MeOH:H2O solvent revealed improved lipid signal-to-noise ratios. The multimodal imaging workflow was successfully applied to a lung tissue section containing a tuberculosis granuloma, demonstrating its applicability to structurally defined, elementally-rich samples.