Non-enzymatic, non-liquid, and/or reagentless digestion and degradation approaches to bottom-up proteomics can be utilised to conserve the resolution of typical MSI with the chemical information affordable by bottom-up proteomics. Current non-enzymatic approaches include thermal decomposition/digestion (TDD) and irradiation with continuous wave lasers -when further combined with ambient MSI, they promise a near-total elimination of sample preparation altogether, dramatically reducing barriers to analysis and improving sample throughput. Argon plasmas currently see use in biomedical techniques such as argon plasma coagulation (APC), which has become commonplace in electrosurgery, and especially in endoscopy . APC utilises a radiofrequency alternating current (through either monopolar or bipolar electrodes) to generate gas discharges, which in turn generate desirable thermal effects in tissue -these thermal effects can be used for haemostasis, devitalisation of tumours, and tissue reduction . One understudied side-product of non-thermal argon plasmas is the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which can be utilised for reactions with various subtrates . In this paper we demonstrate that these radical species, as well as metastable noble gas atoms and free elections, can be exploited for use as a method for in-situ digestion of biological macromolecules for use in MSI.