The most commonly used assay to determine RNA encapsulation in lipid nanoparticles (LNPs) is the ribogreen assay. SEC-MALS, or size exclusion chromatography with multi-angle light scattering, is another technique that can be used characterize large nanoparticles, including lipid nanoparticles (LNPs), for determining the amount of full vs. empty particles when combined with UV and dRI detectors.
Cryo-TEM can provide data on the distribution of encapsulation and size of individual particles in a formulation. In addition, cryo-TEM can visualize bleb formation in LNPs and the lamellarity of your lipid nanoparticle, showing if your LNP is unilamellar or multilamellar. Additionally, a cryo-TEM study uses much less sample than SEC-MALS, requiring only 3ul vs 300ul.
‍This paper in Science shows orthogonal characterization of lipid nanoparticles done by cryo-TEM and SEC-MALS.