Guanine and cytosine are also seen to follow similar profiles, although uracil was not detected, most likely due to significantly lower secondary ion formation probability. (Figure ). The adenine ion intensity had near zero intensity at the surface, which increased at a constant rate until ca 8 nm depth when it levelled off. We interpret the depth at which the adenine signal levels off to approximate to the core of the particle. The observation of adenine intensity before 8 nm is reached, rather than a sharp step up from zero to the value in the core, is interpreted as reflecting a range of PEG overlayer coverage, with the thinner coverage being ablated by sputtering more quickly, whilst thicker areas taking longer to sputter through. This results in a the RNA intensity from the core increasing gradually over a range of depths. The DMG ions were equally seen to be revealed gradually, rather than as a step change, consistent with the PEG profile. Since this is an ensemble measurement, this range in PEG coverage may either be within individual particles, or it may represent different particles with different PEG thickness. It is not possible using this approach to determined which, although extending this beyond this initial proof-of-concept to more LNP formulations, the PEG thickness variability will likely be able to be correlated anticipated LNP structure, e.g. by varying the PEGylated lipid amount. The molecular orientation findings are summarised in a simplified schematic of the molecular structure for DMG-PEG2k in Figure to illustrate the interpretation of the data, but this does not include the PEG thickness variation inferred from the profile breadth.