Mass spectrometry imaging (MSI) -incorporating techniques such as MALDI, DESI, and LD-REIMS -is capable of providing powerful, untargeted insight into the chemical makeup of tissues, cells, and other condensed-phase biological matter . Despite the unparalleled sensitivity and adaptability of MSI, proteins remain a significant stumbling block as both top-down and bottom-up approaches are limited by specific drawbacks; for example, the dynamic range of the proteome can limit top-down proteomic analysis where multiple different proteins of vastly differing mass and concentration are present , a problem that can be further exacerbated by the presence of lipids and small molecules. By contrast, while spectral coverage of both protein fragments and smaller molecules is possible using bottom-up approaches, the use of liquid-phase enzyme solutions can cause delocalisation of analytes as they are desorbed from the surface, consequently representing a bottleneck to spatial resolution in imaging experiments . The sample preparation required for bottom-up analysis is also non-trivial, requiring significant time, expense, and experience. The use of liquid reagents in this manner represents a cap to spatial resolution of around 25µm , with less refined workflows suffering from much lower resolutions.