The authors successfully implement CL-enabled immunolabeling based on biofunctionalized rare-earth element doped nanoparticle-labels.  The research confirms that performing cathodoluminescence imaging on such immunolabelled cancer cells allows specific molecules to be visualized at nanoscale resolution in the context of the cellular ultrastructure.

Light and electron microscopy are commonly used together for understanding the structure-function relationship of biological specimens. Labeling of lipid membranes, proteins, nucleic acids, etc. is done to identify specific structures and to observe cellular processes in a functional setting. However, this method suffers from the diffraction-limited spatial resolution of optical microscopy. Other methods, such as correlative light and electron microscopy, can also be challenging without special tools, due to the complex sample preparation process and image misalignment issues.

An electron microscopy-based approach for localizing individual proteins within the ultrastructural context, on the other hand, promises a new route. In the paper the authors focus on a technique called correlative cathodoluminescence electron microscopy (CCLEM). With CCLEM it’s possible to use next generation protein labels, which can be identified based on their specific optical emission with cathodoluminescence. The work shows that rare-earth element (REE)-based nanocrystals can be used as prospective protein labels due to their bright emission and high electron beam stability. The researchers take a big step further and demonstrate how such nanoparticles can be used as immunoCCLEM labels for targeting folate receptors on cancer cells. 

The authors conclude that these rare-earth element-based nanoparticles show excellent properties as immunolabels, and future investigations should focus on further decreasing the nanoparticle core sizes and developing even brighter nanoparticles, to enable, for example, intracellular protein localization. If you are interested in reading the whole article, please access it here.

Image source: Correlative Cathodoluminescence Electron Microscopy: Immunolabeling Using Rare‐Earth Element Doped Nanoparticles Keevend, R. Krummenacher, E. Kungas, L. R. H. Gerken, A. Gogos, M. Stiefel, and I. K. Herrmann. Small 16 (2020).