Scientists have unveiled a new microscopy technique offering an unprecedented view inside cells, simultaneously revealing intricate structural details and the precise location of proteins in vivid color at nanometer resolution. The breakthrough, dubbed multicolor electron microscopy, was presented at the 70th Biophysical Society Annual Meeting in San Francisco, February 21–25, 2026.
The technique addresses a long-standing limitation in biological imaging, where researchers previously had to choose between high-resolution structural imaging or tracking specific molecules, but not both concurrently. “I’ve always been fascinated by developing new microscopy techniques that can image things we haven’t seen before. We’re building a multicolor electron microscope—a technique that combines the benefits of electron microscopy and fluorescence microscopy,” said Debsankar Saha Roy, a postdoctoral fellow in the laboratory of Maxim Prigozhin at Harvard University.
Traditional fluorescence microscopy utilizes glowing tags attached to proteins, illuminated by visible light to reveal their location. While effective for identifying molecules, its resolution is limited to approximately 250 to 300 nanometers, hindering the clear visualization of individual proteins and lacking comprehensive cellular context, according to Roy. “You see whatever is labeled, but you don’t see everything else around it.”
Electron microscopy, conversely, provides exceptional detail—down to a few nanometers—but traditionally lacked the ability to identify specific molecules in color. Attempts to combine the two methods through sequential imaging and overlaying proved challenging, particularly with large, complex samples.
The Harvard team’s approach bypasses the need for separate imaging sessions. Instead, a single electron beam performs both tasks simultaneously. “We’re not sending in light—we’re sending an electron beam,” Roy explained. “We have probes that you can attach to a protein that emit visible light when excited by electrons. This process is called cathodoluminescence. So from the same electron beam, you get two sets of information: the colored signal from the probes, and also the detailed structural image from the electrons.”
A significant advantage of the new method is its compatibility with existing, widely used fluorescent dyes. The team had previously explored lanthanide nanoparticles as probes for multicolor electron microscopy, but a recent discovery broadened the technique’s accessibility. “The most surprising thing we observed was that standard dyes used in fluorescence microscopy also emit visible light when you excite them with electrons,” Roy said. “That had never been seen before. And these dyes—and their protein labelling methods—are already developed and available; you don’t have to create anything new.”
The researchers have successfully demonstrated the technique’s functionality in mammalian cells and biological tissues, including samples of flies infected with a fungus. A similar approach, utilizing cathodoluminescence microscopy to simultaneously visualize proteins and cellular ultrastructure, was also recently developed, according to research at Harvard University, as reported by Harvard Medical School.
The team is now focused on extending the technique into three dimensions. Currently, the method generates two-dimensional images. Their next goal is to adapt it for use with cryo-electron microscopy, a technique involving flash-freezing samples to preserve their natural state, enabling multi-angle imaging for 3D reconstructions. “We desire to extend this multicolor electron microscopy approach to 3D,” Roy said. “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.”
Researchers have also recently developed a new microscopy technique that allows scientists to see cells in unprecedented detail, merging the strengths of two powerful microscopy methods, as reported by Phys.org.