Scientists have developed a new imaging technique called multicolor electron microscopy. This method combines the capabilities of electron microscopy and fluorescence microscopy, allowing researchers to visualize both the intricate architecture of cells and the specific locations of proteins with nanometer resolution in color.
This innovation addresses the traditional challenge where researchers had to choose between observing fine structural details or tracking specific molecules. The new approach facilitates the study of various cellular processes, including cell signaling and the organization of molecular clusters, while providing spatial context within the cell's structure.
Pioneering Research from Harvard
The research, developed by Debsankar Saha Roy and Maxim Prigozhin at Harvard University, will be presented at the 70th Biophysical Society Annual Meeting in San Francisco from February 21–25, 2026.
Overcoming Traditional Limitations
Traditional fluorescence microscopy, which uses glowing tags on proteins, excels at locating specific molecules but has limited resolution (around 250-300 nanometers) and does not show overall cellular structure. Electron microscopy provides exquisite structural detail (down to a few nanometers) but historically could not identify specific molecules in color. Previous attempts to combine these methods by overlaying separate images faced difficulties with precise alignment.
A Simultaneous Solution
The Harvard team's solution involves using a single electron beam for both tasks simultaneously. Probes attached to proteins emit visible light when excited by electrons, a process known as cathodoluminescence. This single electron beam provides both the colored signal from the probes and the detailed structural image from the electrons.
Leveraging Existing Tools
A significant advantage is the ability to use existing and well-characterized fluorescent dyes. The team previously developed lanthanide nanoparticles for this purpose and later discovered that standard fluorescent dyes also emit visible light when excited by electrons. This observation means that existing protein labeling methods and dyes can be directly applied.
The technique has been successfully demonstrated in mammalian cells and biological tissues, including fungus-infected flies.
The Path Forward: 3D Imaging
Future goals include extending the technique to three dimensions. The researchers plan to adapt multicolor electron microscopy for use with ultrathin sections of cell embedded matrices and cryo-electron microscopy, which would enable 3D reconstructions of cells in their natural state.