Single-Photon-Induced Post-Ionization to Boost Ion Yields in MALDI Mass Spectrometry Imaging

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a rapidly growing method in the life sciences. However, for many analyte classes, its sensitivity is limited due to poor ionization efficiencies. To mitigate this problem, we here introduce a novel post-ionization scheme based on single-photon induced chemical ionization using pulsed RF-Kr lamps. The fine-vacuum conditions of a dual ion-funnel ion source effectively thermalize the evolving MALDI plume and enable ample gas-phase reactions. Injected chemical dopants crucially support fragment-less ionization to [M+H]⁺ /[M-H]^- species. Based on this interplay, numerous glycerophospho-, sphingo-, and further lipids, registered from mammalian tissue sections, were boosted by up to three orders of magnitude, similar to results obtained with laser-based post-ionization (MALDI-2). Experiments with deuterated matrix and dopant, however, indicated complex chemical ionization pathways different from MALDI-2.