dlvr.it
Beyond the Fixed Charge: A New On‐Tissue Derivatisation Strategy Employing Photoionisable Chromophores for Mass Spectrometry Imaging of Amino‐Containing Metabolites
We introduce a novel chemical derivatisation strategy for the UV-activated detection of elusive metabolites. Incorporation of a tocopherol-active chromophore allows for the detection of tagged analytes as photoionised radical cations, selectively induced by a 266 nm laser. Furthermore, high spatially resolved imaging of metabolites has been demonstrated across multiple tissue types.
ABSTRACT
Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) has been widely adopted for the spatially resolved mapping of chemical composition within biological tissues. However, inherent limitations in ionisation efficiencies limit the scope of analyte detection. Currently, methods to enhance molecular coverage have focused on chemical derivatisation of target analyte classes or post-ionisation techniques, namely, laser post-ionisation (MALDI-2). Previously, we observed that under reduced laser fluence conditions, MALDI-2 can be utilised to selectively enhance photoionisation of aromatic analytes. Leveraging these observations, we have conducted a proof-of-concept study to establish a conceptually novel class of derivatisation reagents, employing a tocopherol active chromophore O-linked succinimide (TAC/OS) for the selective derivatisation of primary amines. Using TAC/OS, amino metabolites were selectively detected as the derivatised radical cations in the presence of MALDI-2. Across three tissue types, over 30 metabolites were detected and localised, including 20 amino acids alongside neurotransmitters such as γ-aminobutyric acid (GABA) and dopamine. Imaging at 10 µm pixel size revealed minimal delocalisation, allowing for MSI at near single-cell resolution. Furthermore, we demonstrated the ability of the developed protocol on late-stage pancreatic cancer xenografts.