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.