Bright sub-20-nm cathodoluminescent nanoprobes for electron microscopy

• Published in: Nature nanotechnology Vol. 14; no. 5; pp. 420 - 425
• Main Authors: Prigozhin, Maxim B., Maurer, Peter C., Courtis, Alexandra M., Liu, Nian, Wisser, Michael D., Siefe, Chris, Tian, Bining, Chan, Emory, Song, Guosheng, Fischer, Stefan, Aloni, Shaul, Ogletree, D. Frank, Barnard, Edward S., Joubert, Lydia-Marie, Rao, Jianghong, Alivisatos, A. Paul, Macfarlane, Roger M., Cohen, Bruce E., Cui, Yi, Dionne, Jennifer A., Chu, Steven
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2019; Nature Publishing Group
• Subjects: 639/301/357/354; 639/624/399/354; 639/925/357/354; Biomolecules; Cathodoluminescence; Chemistry and Materials Science; Electron imaging; Electron microscopy; Emission measurements; Fluorescent Dyes - chemistry; Letter; Localization; Materials Science; Medical imaging; Microscopy; Microscopy, Electron, Transmission; Molecular biology; Morphology; Nanoparticles; Nanoparticles - chemistry; NANOSCIENCE AND NANOTECHNOLOGY; Nanotechnology; Nanotechnology and Microengineering; Optimization; Photon emission; Protein interaction; Proteins; Ultrastructure
• ISSN: 1748-3387; 1748-3395
• DOI: 10.1038/s41565-019-0395-0

Electron microscopy has been instrumental in our understanding of complex biological systems. Although electron microscopy reveals cellular morphology with nanoscale resolution, it does not provide information on the location of different types of proteins. An electron-microscopy-based bioimaging technology capable of localizing individual proteins and resolving protein–protein interactions with respect to cellular ultrastructure would provide important insights into the molecular biology of a cell. Here, we synthesize small lanthanide-doped nanoparticles and measure the absolute photon emission rate of individual nanoparticles resulting from a given electron excitation flux (cathodoluminescence). Our results suggest that the optimization of nanoparticle composition, synthesis protocols and electron imaging conditions can lead to sub-20-nm nanolabels that would enable high signal-to-noise localization of individual biomolecules within a cellular context. In ensemble measurements, these labels exhibit narrow spectra of nine distinct colours, so the imaging of biomolecules in a multicolour electron microscopy modality may be possible. Lanthanide-doped nanoparticles could be used as labels for the imaging of biomolecules, potentially leading to a multicolour modality in electron microscopy.