Characterizing the effect of MeV ion beam irradiation on biological tissues is important for proton beam therapy, which is routinely used as a form of cancer treatment. It is also important for optimizing protocols for multimodal elemental and molecular imaging. Elemental mapping of trace elements in tissues has been carried out for a long time using nuclear microprobe analysis. However, the effect of MeV ion beams on biological samples is largely unexplored. These effects have been explored in Surrey using two mass spectrometry imaging (MSI) techniques – matrix-assisted laser desorption electrospray (MALDI) and desorption electrospray ionization (DESI). The combination of these techniques with ion beam analysis (IBA) presents a few challenges, namely substrate compatibility and de-localization of elemental markers during measurements. As such, MeV-secondary ion mass spectrometry (SIMS) is being explored as an alternative technique for molecular imaging of biological tissues. MeV SIMS, unlike conventional keV SIMS, allows the detection of intact molecules, making it a prime candidate for the molecular analysis of biological samples. This presents an opportunity to benchmark the capabilities of MeV SIMS against established and widely used techniques such as DESI and MALDI. Experiments carried out at Surrey (reported at the ICNMTA 2020) observed that proton beam-induced damage could be mitigated through the application of a MALDI matrix (employed in MALDI as an ionization aid and sample protection). Thus, the role of this matrix is explored in MeV SIMS experiments.