A cryogenic preparation protocol is developed to examine LNPs in vitreous ice sequentially on different areas of the same sample by TEM and then Cryo-OrbiSIMS. To test the capability of cryogenic OrbiSIMS profiling for the characterisation of the surface and subsurface chemistry of the LNPs, we analysed a model formulation comprising mRNA and 4 lipids; DMG-PEG2k and cholesterol, Dlin-MC3-DMA as the ionisable lipid and DSPC as the helper lipid (Table ) formed using microfluids. The nanoparticle suspension in phosphate buffered saline (PBS) was deposited onto a plasma etched 10 nm thick amorphous carbon film with regularly spaced 2.4 µm diameter holes supported by copper TEM grids. These were blotted to modulate thickness before plunging into liquid ethane, after which they were transferred under liquid nitrogen for cryo-TEM imaging (-172°C). The particles were found by TEM to be relatively monodisperse, with their diameters distributed around a mean of 60-80 nm (Figure ) while with DLS they were estimated to be slightly larger with a mean diameter of 91 nm and a PDI of 0.03 (Figure ).