Innovative microscope at Montana State lets scientists explore molecules in 3-D, ultra-high resolution

Thanks to an innovative piece of technology, researchers at Montana State University are now able to conduct scientific exploration at a whole new level — a very, very small one.

Last month, MSU powered up the second ultra-high resolution cryogenic transfer electron microscope, or cryo-TEM, in the northern Rocky Mountain region. The microscope, which was built in the Czech Republic before being partially disassembled and shipped to Bozeman, has the capability to create high-resolution and three-dimensional images on a cellular level with more clarity than any other tool.

It is the only TEM at any university in Montana, Idaho, Wyoming or the Dakotas. The only other such microscope in the region is at the National Institutes of Health’s Rocky Mountain Laboratories in Hamilton.

“This microscope is capable of really high-resolution imaging, down to a tenth of a nanometer, which we call an angstrom,” said Martin Lawrence, a professor in Department of Chemistry and Biochemistry in MSU’s College of Letters and Science and the facility director of MSU’s Cryo-Electron Microscopy Laboratory, also called the Cryo-EM Lab. An angstrom is a unit of measurement so small it is chiefly used for wavelengths of light.

“This addition to our array of research infrastructure offers new and exciting opportunities into a variety of fields here at MSU,” said Jason Carter, vice president for research, economic development and graduate education. “It will serve as a resource for scientists both across the MSU community and in the wider world of academia.”

The microscope is so sensitive, said Lawrence, that its lenses are suspended on air cushions to avoid even the tiniest vibrations, which can distort the resulting images.

“At those kinds of resolutions, if you have even a little bit of shaking it’s going to blur the image, just like if you’re trying to hold a camera steady,” Lawrence said. “If you have changes in temperature, you’ll have very minor contractions or expansions that will shift things. Acoustic waves and even foot traffic can cause vibrations that can be a problem.”

That’s why MSU undertook a full remodel of the Cryo-EM Lab to accommodate the new microscope, which included an expansion of the space to fit the 8-foot cube-shaped chamber that houses it, which contains a shaft that reaches from floor to ceiling. The project totaled $3.8 million including the cost of the microscope, paid for with funding from the National Science Foundation, Murdock Charitable Trust and MSU’s Office of Research, Economic Development and Graduate Education.

From the time the microscope arrived in January, it took nearly eight weeks reassemble it. Along with the microscope, the Cryo-EM lab now has an entire room dedicated to the computers that take the images captured by the TEM — as many as 100,000, up to 50 per second — and stitch them into a 3-D model of something normally invisible to the naked eye.

Its uses are incredibly broad, according to Lawrence. It lets scientists see with unprecedented clarity individual proteins within cells and examine structures previously illustrated by grainy, black and white images. The TEM is particularly useful in virology, allowing researchers to get a clear enough view to identify exactly how viruses infect their hosts.

One recent project used TEM technology to explore viruses that inhabit Yellowstone National Park’s hot springs. For years, researchers had known such viruses existed and that they infected the single-celled organisms that live in thermal features. But because scientists didn’t have a clear image of what the viruses looked like, it couldn’t be said for certain exactly how they latched onto their hosts.

Thanks to the TEMs at other institutions, researchers now know the Yellowstone viruses’ cellular structures looks relatively similar to the now-recognizable SARS-CoV-2 virus, with tiny spikes that allow it to attach to its host organism. By taking thousands of images, each at a slightly different angle, and averaging them, TEM technology allows scientists to unlock new insights about some of the world’s smallest organisms.

Now, all that exploration can be done in-house at MSU, Lawrence said. Plus, when combined with the subzero technology MSU’s Cryo-EM Lab is known for, the microscope will allow materials scientists, biologists, virologists and other researchers to examine organic materials in a more natural state.

That’s because electron microscopes like TEM produce images by shooting a beam of electrons directly at a sample. This can quickly destroy organic matter like plants, making it much more difficult to see their natural makeup on a molecular level.

But the Cryo-EM Lab has a tool called a plunge freezer that uses liquid propane or ethane to freeze samples so quickly that their molecules don’t have time to reorganize into the crystal structures generally associated with freezing. Instead, their molecules trapped exactly as they were when they plunged into the freezer in a glassy form called vitreous ice.

In addition to facilitating projects across nearly a dozen departments and centers at MSU, Lawrence said the TEM will serve as a resource to scientists across the region. Researchers from other universities have already begun sending samples to put the technology to use.

“It will hugely benefit this campus and I’m glad we’ll be able to make it available to other people,” he said.