There was a high intensity of PEG signal at the beginning of the analysis which decreased with etching, consistent with the expectation that the PEG portion of the molecule orients outwards for the LNPs. Notably the PEG profile, which is constructed from sodiated PEG ions, does not correlate with the sodium profile derived from the Na2Cl + ion (Figure ). This suggests that the sodiated-PEG adduct ions are reflective of an ionic association in the hydrated sample which is an established phenomenon for PEG, and that the intensity of these ions is reflective of the amount of PEG in the sample, rather than the Na2Cl + distribution. Cationization of PEG through doping prior to SIMS analysis has previously been used to increase the secondary ion yield of oligomers. However, in our experiments the sodium from the PBS particle suspension has enhanced the yield of the PEG from the frozen sample and represents the actual hydrated sample chemistry rather than an artifact of preparation. Notably the PEG in the DMG-PEG2k component spectra in Figure is also dominated by sodiated secondary ion adducts.