Depth profiles of organic delta layer standards show that the depth accuracy and resolution is dependent on the secondary ions used as well as the primary ions and their energy. Without standard samples comprising molecules from the LNPs, it is difficult to differentiate broadening due to sputter effects from actual concentration gradients representing component intermixing or heterogeneous particle chemistries. Therefore, the depth resolution expected on these spherical, real-world frozen-hydrated LNP samples is difficult to estimate. We have therefore been cautious in our interpretation of the LNP profiles. While standards for depth profile resolution estimation for LNP components are not readily available, these could be envisaged to be supported lipid bi-layers which would have the advantage of being flat, or single-and mixed-component micelles which would well represent the particulate geometry and approximate dimensions. This would allow the variability in PEG overlayer thickness inferred from the broadness of profiles seen herein to be ascribed to actual or experimental depth resolution limits.