AFM‐TEM correlation microscopy and its application to lipid nanoparticles

Abstract

So far, only a few articles have demonstrated the possibility of correlated AFM‐TEM imaging – sequential imaging of the same individual objects using atomic‐force microscopy (AFM) and transmission electron microscopy (TEM). The current work contributes to the development of this approach by giving a step‐by‐step procedure, which yields pairs of correlated AFM‐TEM images. We describe the application of correlation AFM‐TEM microscopy to lipid nanoparticles (small extracellular vesicles and liposomes). The sizes of individual particles measured by the two methods were in good agreement, taking the tip broadening into account. The correlated AFM‐TEM imaging can be valuable for single‐particle analysis and nanometrology.

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“…For the AFM imaging, NPs were deposited onto TEM grids (amorphous carbon) rather than mica or graphite, which are commonly used as substrates. We chose the grids treated with the glow discharge because the adsorption of the NPs onto their surface was relatively high, and they were previously used as substrates for the AFM imaging [ 51 ].…”