Unimodal Imaging of Monovalent Metal-Chelator Complexes and Lipids by MALDI Imaging Mass Spectrometry

Careful regulation of monovalent metal ions (M⁺) is necessary to maintain a functional cellular system. Of these ions, appropriate sodium (Na⁺) and potassium (K⁺) concentrations are particularly integral for electrochemical signaling, as well as the secondary transport of nutrients and waste. Dysregulation of M⁺ homeostasis can disrupt these mechanisms, potentially influencing the metabolism of downstream biomolecules such as lipids. Thus, the relationship between M⁺ abundances and related biomolecular distributions must be elucidated to better understand the physiology of healthy and disordered tissues. Traditional techniques for imaging biological metal distributions include SIMS, LA-ICP-MS, and XRF; however, these capabilities are limited to elemental analysis or the analysis of molecular fragments and must be paired with other modalities to visualize distributions of more complex biomolecules within the same or similar samples. Conversely, matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a powerful tool often used for mapping such biomolecular distributions, but current methods are unable to detect metals within tissue. This study illustrates a novel methodology that adds metal detection to the MALDI IMS repertoire through which the simultaneous detection of M⁺ metals and lipids is achievable. Using a robotic sprayer for homogeneous application, on-tissue deposition of the chelator deferiprone (DEF) enables subsequent detection of the ionizable metal-chelator complex by MALDI without hindering lipid detection. Our work provides proof-of-concept data for the simultaneous detection of K⁺, Na⁺, and intact lipids using MALDI IMS.