Scientists have unveiled a pioneering imaging technique, multicolor electron microscopy, that integrates electron and fluorescence microscopy. This method allows researchers to view both the cellular architecture and protein locations in vivid colour at nanometre resolution. The novel approach addresses a long-standing limitation in biological imaging, where researchers previously had to choose between structural details or molecular tracking.
The development was led by a team at Harvard University, and the findings will be presented at the 70th Biophysical Society Annual Meeting in San Francisco from February 21–25, 2026. Debsankar Saha Roy, a postdoctoral fellow in Maxim Prigozhin’s laboratory, highlighted the innovative nature of the project, stating, “We’re building a multicolour electron microscope — a technique that combines the benefits of electron microscopy and fluorescence microscopy.”
Traditional fluorescence microscopy, while effective in locating molecules via glowing tags, struggles with resolution limitations. Roy explained, “The resolution is limited to about 250 to 300 nanometres, so you can’t see individual proteins clearly. But the bigger issue is that you don’t see the structure of the cell.” In contrast, electron microscopy excels in detailing cellular structures but lacks the capability to identify specific molecules in colour.
The Harvard team’s solution involves using a single electron beam to perform both tasks simultaneously. “We’re not sending in light — we’re sending an electron beam,” Roy stated. The process, known as cathodoluminescence, uses probes that emit visible light when excited by electrons, providing both a coloured signal and a detailed structural image.
A significant advantage of this technique is the use of existing fluorescent dyes, which are well-characterized and widely available. The team discovered that these dyes emit visible light when excited by electrons, a phenomenon previously unseen. This capability allows researchers to utilize established labelling methods without the need for new creations.
Having demonstrated success in mammalian cells and biological tissues, including fungus-infected flies, the researchers aim to extend the technique to three-dimensional imaging. The next step involves adapting it for cryo-electron microscopy, which preserves cells in their natural state, enabling 3D reconstructions. Roy stated, “We want to extend this multicolor electron microscopy approach to 3D. To get there, we aim to implement this technique in ultrathin sections of cell-embedded matrices and/or in cryo-electron microscopy — that’s the next step.”
The continued development of multicolour electron microscopy holds promise for advancing our understanding of cellular processes, with potential applications in various fields of biological research.
