Inspired by the sea and the sky, a biologist invents a new kind of microscope

With samples suspended in any type of liquid, the apparatus may produce clear pictures.

If you've ever possessed a telescope, you've undoubtedly tried peering through the incorrect end to see if it can be used backwards, like a microscope. Unfortunate news: It doesn't.

Now, a group of scientists has developed a method for doing it after being inspired by the peculiar eyes of a marine species. They have developed a new sort of microscope that can be used to see samples floating in any type of liquid, including the interiors of transparent organs, while keeping enough light to enable high magnification. They did this by flipping the mirrors and lenses used in some types of telescopes. The structure might enable researchers to analyze minute details like the long, slender axons that link neurons in the brain or specific proteins or RNA molecules inside of cells.

According to Kimani Touissant, an electrical engineer at Brown University, "it's good to see even something as fundamental as a lens could still generate attention and there's still potential there to do some work that would assist a lot of people." In his research, he utilizes lasers to carve patterns into gels that resemble collagen and serve as cellular scaffolding. He claims the design might be effective in this work.

Light focused on a sample at a very high magnification can scatter away from it, obscuring and darkening the picture. In order to circumvent this issue, researchers employing conventional lens-based microscopes cover their sample with a small coating of oil or water before dipping the lens of their instrument into the liquid to reduce the amount of light scattering. Nevertheless, this approach necessitates the use of instruments with specific lenses for each type of liquid, which makes it a costly and difficult operation and restricts the methods for sample preparation.

Now comes Fabian Voigt, creator of the novel design and a molecular scientist at Harvard University. In a book about animal eyesight, he came across the peculiar case of scallops' eyes. Scallops have mantles covered with hundreds of tiny blue dots, each of which has a curved mirror at its rear, unlike other animals whose eyes have retinas that transfer pictures to the brain. Each eye's inner mirror reflects light back onto the creature's photoreceptors as it travels through the lens, creating a picture that the scallop may then use to react to its surroundings.

Voigt, an avid astronomer since he was a youth, noticed that the scallop's eye design resembled a type of telescope called the Schmidt telescope that was developed approximately 100 years ago. This curved mirror technology is used by the Earth-orbiting Kepler Space Telescope to amplify distant light from exoplanets. In order to make the design fit within a microscope, Voigt decided to reduce the size of the mirror, switch to laser lighting, and fill the gap between the mirror and the detector with liquid to reduce light scattering.

Following those specifications, Voigt and his colleagues created a prototype. Light enters the apparatus from the top, travels through a curved plate that compensates for the curvature of the mirror, and then bounces off a mirror before hitting a sample and magnifying it. According to Voigt, the curved mirror may enlarge the picture similarly to a lens. It streamlines the procedure by enabling researchers to examine materials suspended in any form of liquid. The design, according to Voigt, may be especially helpful to scientists who examine organs or even entire creatures like mice or eggs that have had their color removed intentionally.

The scientists used translucent samples, such as the muscles in a tadpole's tail, a mouse brain, and a whole chicken embryo, to test their prototype by shining a laser on them. These pictures, although employing a simpler design and allowing for greater flexibility in how researchers prepare materials, the researchers reported last month in Nature Biotechnology, were just as clear as those that could be obtained with traditional optical microscopes.

According to Adam Glaser, an engineer at the Allen Center for Neural Dynamics working on brain mapping, the mirror design might be helpful to researchers attempting to track the route of a mouse's axons as they wind around the brain. Axons can be dozens of millimeters long but just a few nanometers wide, making it difficult to map the whole mouse brain. Using commercially available microscopes is also expensive and difficult to use since they need a lot of lenses. The new design, however, could be simpler to use because it only needs one mirror and gives researchers greater flexibility in how they prepare their brain samples thanks to its ability to scan through any sort of liquid.

Glaser continues by saying that the new microscope may also be useful to researchers looking at RNA molecules inside neurons, which may indicate which genes are expressed by each cell. He claims that drawing inspiration from astronomy is a fantastically effective and original approach to conduct science.