Inspired by the sea and the sky, a biologist invents a new type of microscope | Science

Anyone who has ever owned a telescope has probably tried looking through the wrong end to see if it worked in reverse—that is, like a microscope. Spoiler alert: It’s not.

Now, a team of researchers inspired by the strange eyes of a sea creature has come up with a way to do it. By reversing the mirrors and lenses used in certain types of telescopes, they created a new kind of microscope that can be used to image samples floating in any kind of liquid—even the insides of transparent organs—while retaining enough light to allow high magnification. The design could help scientists achieve high enough magnification to study small structures such as the long, thin axons that connect neurons in the brain or individual proteins or RNA molecules inside cells.

“It’s good to see that even something as basic as a lens can still generate interest and there’s still room to do work that would help a lot of people,” said Kimani Touissant, an electrical engineer at Brown University. He says the design could be useful in his work, in which he uses lasers to etch patterns into gels that mimic collagen and act as scaffolds for cells.

At very high magnification, light trained on a sample can scatter around it, blurring and obscuring the image. To overcome this problem, scientists using traditional lens-based microscopes cover their sample with a thin layer of oil or water, then submerge their device’s lens in the liquid, minimizing the amount of light scattering. But this technique requires the instruments to have different lenses for different types of liquids, making it an expensive, delicate process and limiting the ways in which samples can be prepared.

Enter Fabian Voigt, a molecular biologist at Harvard University and inventor of the new design. He was reading a book on animal vision when he came across the strange case of clam eyes. Unlike most animals, whose eyes have a retina that sends images to the brain, clams have a mantle covered with hundreds of tiny blue dots, each containing a curved mirror on its back. As light passes through the lens of each eye, its internal mirror reflects the light back to the creature’s photoreceptors to create an image, which then allows the clam to respond to its environment.

An amateur astronomer since his youth, Voigt realized that the design of the clam’s eye resembled a type of telescope invented nearly 100 years ago called a Schmidt telescope. The Earth-orbiting Kepler space telescope uses a similar curved mirror design to magnify distant light from exoplanets. Voigt realized that by shrinking the mirror, using lasers for light, and filling the space between the mirror and the detector with liquid to minimize light scattering, the design could be adapted to fit inside a microscope.

So Voigt and his colleagues built a prototype based on those specifications. Light enters from above, passes through a curved plate that corrects the curvature of the mirror, then bounces off the mirror to strike a sample and magnify it. A curved mirror can magnify an image like a lens, Voigt says. This allows researchers to look at samples suspended in any kind of liquid, simplifying the process. Voigt says the design could be particularly useful for researchers studying organs or even whole organisms, such as mice or embryos, that have been made completely transparent by artificially removing their pigment.

The researchers tested their prototype by shining a laser on transparent samples, including muscles in the tail of a tadpole, a mouse brain and a whole chicken embryo. These images, reported by researchers last month in Natural Biotechnologieswere as clear as those that could be achieved with conventional optical microscopes, despite using a simpler design and allowing more flexibility in how researchers prepare samples.

The mirror’s design could prove useful for researchers seeking to trace the path of mouse axons as they travel through the brain, said Adam Glaser, an engineer at the Allen Institute for Neural Dynamics who works on brain mapping. Axons can be tens of millimeters long but only nanometers wide, making mapping the entire mouse brain a herculean task. It is also expensive to use commercially available microscopes that require multiple lenses and are difficult to operate. The new design, by contrast, may be easier to use because it requires only one mirror, and because it can image through any type of liquid, it allows researchers to be more flexible in how they prepare their brain samples.

Glaser adds that the new microscope could also help researchers looking at RNA molecules in neurons that could reveal what genes each cell expresses. “Borrowing from astronomy is a wonderfully efficient and creative way of doing science,” he says.

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