A technique borrowed from astronomy is helping sharpen microscopic imaging of complex biological subjects that can present obstacles to even very high-tech light microscopes.

Light passing through and reflecting off biological samples can bend in ways difficult to predict, yielding microscope images that are often challenging to interpret.

An imaging technology based on a form of adaptive optics often employed in astronomy developed by scientists at the Howard Hughes Medical Institute in Maryland, can quickly correct for distortions in the image and provide images that are sharper and in higher resolution in large amounts of biological sample material.

The technique works in types of tissues that don't scatter light, providing the capability of imaging model organisms important in many areas of biological research, like zebrafish or the roundworm.

Writing in the Nature Methods, HHMI researchers Eric Betzig and Kai Wang report the technique can bring into focus tiny, dividing structures and components of nerve cells inside a zebrafish's living brain, details that remain indistinct and blurry in a microscope without the adaptive opics.

"The results are pretty eye-popping," Betzig says. "This really takes the application of adaptive optics to microscopy to a completely different level."

The technique takes its cue from astronomy, which has developed adaptive optics using deformable telescope mirrors to cancel out the distortion of cosmic observations caused by turbulence in the Earth's atmosphere.

The microscopic technique uses a similar principle, collecting images of the target from many different angles to determine the correction to be applied.

"We kept on pushing this technology, and it turns out it works," says Kai Wang, a postdoctoral researcher 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."

The adaptive optics work automatically.

"You don't have to slow down or do anything different," Betzig says. "It's just happening in the background as you're running the microscope."

"Our technique is really robust, and you don't need anything special to apply our technology," adds Wang. "[In the future] it could be a very convenient add-on component to commercially available microscopes."

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