Direct imaging of single cells and tissue at sub‐cellular spatial resolution using transmission geometry MALDI MS

Discussions about MALDI imaging frequently turn to the topic of spatial resolution and the eff orts of some researchers in the field to push towards routine imaging of tissue sections at a cellular scale. Some factors that limit resolution are, the size of the focused desorption laser beam and analyte delocalization from the solution-based sample preparation. With solvent-free matrix application techniques analyte delocalization is less of a concern and the size of the focused laser is the major limiter of spatial resolution. In the Special Feature, Professor Caprioli and co-workers at Vanderbilt University demonstrate a new instrumental approach for improving spatial resolution. They have modifi ed a MALDI-TOF system to use transmission-mode geometry, in which the desorption laser is focused onto the matrix crystals from behind and through the target and sample rather than conventional front-side illumination where the laser is focused onto the crystals directly. They show that by moving the laser source behind the sample target, they can optimize the laser focus to achieve cellular resolution for MALDI imaging.