A new type of microscope inspired by James Webb sees molecules in 6D

Its resolution is 1.5 times better compared to state-of-the-art techniques
Ayesha Gulzar
Radially and azimuthally polarized multi-view reflector (raMVR)
Radially and azimuthally polarized multi-view reflector (raMVR)

Washington University in St. Louis 

Researchers developed a new technology to see very small molecules in 6D. Inspired by the James Webb Space Telescope (JWST) design, the latest technology uses mirror segments to sort and gather light on a microscopic scale and take three-dimensional images of molecules both in position and orientation.

The microscopic world

From the universe to the tiniest subatomic particle, objects in our world exist in a mind-boggling array of sizes. With microscopes, we can look directly at some of the objects and processes that are too small to be seen with the naked eye.

This has allowed us to make great leaps in our scientific understanding. However, biological molecules are so tiny that only our very best electron microscopes can give us fuzzy, grainy images. That's why precise imaging relies more heavily on computer processing to sort out orientation after an image has been captured.

"Think of creating a color picture when all you have are gray-scale camera sensors. You could try to recreate the color using a computational tool, or you can directly measure it using a color sensor, which uses various absorbing color filters on top of different pixels to detect colors," said Matthew Lew, associate professor of electrical and systems engineering at the McKelvey School of Engineering at Washington University in St. Louis.

The new microscope view molecules in 6D

Now researchers from the McKelvey School of Engineering at Washington University in St. Louis developed a new microscope called the radially and azimuthally polarized multi-view reflector (raMVR). The microscope relies on gathering as much light as possible, just like the James Webb Telescope. But instead of seeing distant objects, the new technology uses that light to distinguish distinct properties of small, fluorescent molecules bound to proteins and cell membranes.

"The setup is partially inspired by telescopes. It's a very similar setup. Instead of the familiar honeycomb shape of the JWST, we use pyramid-shaped mirrors," Zhang said, a recent Ph.D. graduate and author of the study.

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The raMVR microscope can be used for imaging the three-dimensional (3D) positions and 3D orientations of single molecules, with precisions of 10.9 nm and 2.0° over a 1.5-micron depth range. Its resolution is 1.5 times better compared to state-of-the-art techniques.

The raMVR microscope uses polarization optics called waveplates along with its pyramid-shaped mirrors to separate light into eight channels, each representing a different piece of the molecule's position and orientation.

Researchers note that the raMVR microscope is not a small technology. But smaller isn't always better.

"At the cutting edge of engineering physics, we often have to make tradeoffs to make our instruments compact. Here, we decided to take a different tack: How could we use every precious bit of light to make the most precise measurement possible? It's absolutely fun to think differently about the architecture of a microscope, and here, we think the newfound 6D imaging performance will enable new scientific discoveries in the near future," said Professor Matthew Lew.

The study is published in the journal Nature photonics.