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MADRID, February 23, 2026 (EUROPA PRESS) –
Researchers at Harvard University have developed a fresh imaging technique that combines the strengths of two powerful microscopy methods, offering unprecedented visualization of cellular structures and protein locations in vibrant color and at nanoscale resolution. This advancement, presented at the 70th Annual Meeting of the Biophysical Society in San Francisco from February 21-25, 2026, represents a significant step forward in biological imaging.
The new approach, called multicolor electron microscopy, overcomes a longstanding challenge in biological imaging: the need to choose between observing fine structural details or tracking specific molecules. This technique opens new avenues for studying everything from cellular signaling to the organization of molecular groups within cells, while precisely pinpointing where these processes occur within the cellular architecture. Understanding these processes at this level of detail is crucial for developing new therapies and understanding disease mechanisms.
“I’ve always been fascinated by developing new microscopy techniques that allow us to visualize things we haven’t seen before. We are building a multicolor electron microscope, a technique that combines the advantages of electron microscopy and fluorescence microscopy,” said Debsankar Saha Roy, a postdoctoral researcher in Maxim Prigozhin’s laboratory at Harvard University.
Traditional fluorescence microscopy involves attaching light-emitting markers to proteins of interest and then shining visible light on the sample to illuminate them. While excellent for locating specific molecules, this method has limitations. “The resolution is limited to about 250 to 300 nanometers, so you can’t clearly see individual proteins,” Roy explained. “But the biggest problem is that you don’t see the structure of the cell. You see what is labeled, but not everything around it.”
Electron microscopy, can reveal cellular structures in exquisite detail, even down to a few nanometers. However, it has traditionally been unable to identify specific molecules in color. Scientists have attempted to combine both approaches by taking separate images with each method and then overlaying them, but accurately aligning the images, especially in large samples like brain tissue, has proven extremely hard.
The Harvard team’s solution is innovative: instead of using two separate imaging sessions, they utilize a single electron beam to perform both tasks simultaneously. “We don’t send light, but an electron beam,” Roy stated. “We have probes that can attach to a protein that emits visible light when excited by electrons. This process is called cathodoluminescence. From the same electron beam, you obtain two sets of information: the colored signal from the probes and the detailed structural image from the electrons.”
A key advantage of this technique is that researchers can utilize existing fluorescent dyes, which are widely available and well-characterized. The team had previously developed lanthanide nanoparticles as probes for multicolor electron microscopy and were working to attach them to proteins.
More recently, the team made a surprising discovery when placing common fluorescent dyes under the electron microscope. “The most surprising thing we observed was that standard dyes used in fluorescence microscopy also emit visible light when excited with electrons,” Roy noted. “This had never been seen before. And these dyes, and their protein labeling methods, are already developed and available; there’s no need to create anything new.”
The team has already demonstrated that the technique works in mammalian cells and biological tissues, including fruit flies infected with fungi.
Looking ahead, the researchers aim to extend the technique to three dimensions. Currently, the method produces flat, two-dimensional images. The next challenge is to adapt it for use with cryo-electron microscopy, a technique that involves rapidly freezing samples, preserving cells in their natural state, and allowing scientists to image them from multiple angles to create 3D reconstructions.
“We seek to extend this multicolor electron microscopy approach to 3D,” Roy concluded. “To achieve this, our goal is to implement this technique on ultrafine sections of embedded cell matrices or in cryo-electron microscopy; that is the next step.”
