Enabling Cellular Resolution Molecular Pathology for Surgical Interventions Using Laser Desorption – Rapid Evaporative Ionization Mass spectrometry

Laser desorption ionization (LDI) is generally considered to be an inferior ionization modality to matrix assisted LDI (MALDI), providing information solely on lipids with low sensitivity. The current study demonstrates that the combination of ambient LDI with in-source surface-induced declustering provides sensitivity and chemical coverage comparable to MALDI. The setup was characterised for infrared laser desorption using two different laser systems and was successfully used for ambient mass spectrometric imaging. 5 µm spatial resolution was achieved enabling single-cell resolution imaging, while metabolites and lipids ranging from amino acids through carbohydrates and nuclear bases to complex glycolipids were successfully detected. The technique was also tested as a platform for MS-guided surgery, raising the possibility of using a single technique for generating histological and in-vivo data. The results suggest that the method can be an important step forward in histological classification for surgery and pathology environments, potentially offering a versatile platform for generating both histological and in vivo data.