illustration by Leif Parsons

Sharper Image

A big problem in microscopy is that biological samples bend and distort light in unpredictable ways. The larger and more complex the specimen, the more erratic the light—and the fuzzier the resulting image. To circumvent this obstacle, Janelia Group Leader Eric Betzig created a new microscopy technique that borrows from astronomy and ophthalmology.

Astronomers correct for atmospheric distortion by shining a laser skyward in the direction they plan to observe, and then measuring the distortion of the returning light. Betzig and his colleagues duplicated this process on a smaller scale by figuring out how a tissue sample distorts infrared light. They corrected for aberrations in the returning light with a method ophthalmologists use to adjust for the movement of a patient’s eyes when capturing retinal images.

The techniques allowed Betzig and his colleagues to bring into focus the subcellular organelles and fine, branching processes of nerve cells deep in the brain of a living zebrafish. “The results are pretty eye-popping,” says Betzig, who published the method in the June 2014 issue of Nature Methods.

A subset of neurons in the brain of a living zebrafish embryo. Portions of the video show what one would see with and without Betzig’s technique.

“We kept on pushing this technology, and it turns out it works,” explains Kai Wang, a postdoctoral fellow in Betzig’s lab. “When we compare the image quality before and after correction, it’s very different. The corrected image tells a lot of information that biologists want to know.”