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Bringing Molecules Into View: Record-Breaking High-Resolution Optical Technique Resolves Objects as Small as 0.5 Nanometers

Conventional wisdom holds that optical microscopy can't be used to "see" something as small as an individual molecule. But science has once again overturned conventional wisdom. Secretary of Energy, Nobel laureate and former director of the Lawrence Berkeley National Laboratory (Berkeley Lab) Steven Chu led the development of a technique that enables the use of optical microscopy to image objects or the distance between them with resolutions as small as 0.5 nanometers -- one-half of one billionth of a meter, or an order of magnitude smaller than the previous best.

"The ability to get sub-nanometer resolution in biologically relevant aqueous environments has the potential to revolutionize biology, particularly structural biology," says Secretary Chu. "One of the motivations for this work, for example, was to measure distances between proteins that form multi-domain, highly complex structures, such as the protein assembly that forms the human RNA polymerase II system, which initiates DNA transcription."

Secretary Chu is the co-author of a paper now appearing in the journal Nature that describes this research. The other authors are Alexandros Pertsinidis, a post-doctoral researcher and member of Chu's research group at the University of California (UC) Berkeley, who is now an assistant professor at the Sloan-Kettering Institute, and Yunxiang Zhang, a member of Chu's research group at Stanford University.

According to a law of physics known as the "diffraction limit," the smallest image that an optical system can resolve is about half the wavelength of the light used to produce that image. For conventional optics, this corresponds to about 200 nanometers. By comparison, a DNA molecule measures about 2.5 nanometers in width.

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