Researchers have developed a revolutionary microscope that uses an incredibly powerful laser to make previously invisible cellular structures easier to see. The technology dramatically improves image clarity, allowing scientists to examine small proteins that conventional electron microscopes struggle to capture. It could eventually reveal how tiny molecular machines interact inside cells, providing an unprecedented look at the hidden workings of life.
Almost a century ago, a breakthrough in microscopy gave scientists an entirely new way to examine the inside of cells. Known as phase contrast, the technique made previously faint or nearly invisible cellular structures much easier to distinguish. Its importance was recognized with a Nobel Prize in 1953.
Now, physicists at the University of California, Berkeley, have brought that same principle to electron microscopy, a technology capable of magnifying objects roughly 10,000 times more than conventional light microscopes.
The researchers have developed a device called a laser phase plate that could significantly improve cryoelectron microscopy (cryo-EM). This powerful imaging method has transformed the study of protein structures and helped speed up drug discovery over the past decade. Even so, it has a major limitation: Most human proteins are so small that obtaining clear images of them remains extremely difficult.
The new laser technology could help overcome that obstacle, potentially allowing scientists to image proteins as small as one-third the size of those that challenge current microscopes.
An even greater impact could come from improvements to cryoelectron tomography (cryo-ET). This newer approach combines images captured from multiple angles to construct three-dimensional views of proteins and other molecules. Unlike techniques that study isolated molecules in a solution, cryo-ET can reveal how proteins are arranged and interact within their natural cellular surroundings.
“Cryo-EM has become the new, fastest-growing method for resolving the structure of biological macromolecules, and cryo-ET is expected to show how these molecules work together in their natural, cellular context,” said Holger Müller, a UC Berkeley professor of physics and faculty scientist at Lawrence Berkeley National Laboratory who led the development effort. “But because of signal-to-noise limitations, the majority of human and animal proteins are too small to be analyzed by these methods. The increase in signal-to-noise ratio provided by this laser phase plate is expected to overcome these important limitations.”
https://www.sciencedaily.com/releases/2026/10/261021231230.htm
