Freeze Frame

Powerful (and rare) electron microscopes keep Penn State researchers on the cutting edge.

Arctica microscope at Millennium Science Complex, photo by Nick Sloff '92 A&A

The Cryo Electron Microscopy Facility, established in 2017, takes full advantage of the construction of the Millennium Science Complex’s basement labs, which are structurally independent from the rest of the building. This creates stability that allows the lab’s state- of-the-art electron microscopes to produce atomic resolution. The combination of the technology and the isolated rooms allows researchers to explore proteins, viruses, or materials in a different way.

“Basically, you’re looking at something without your glasses, and when it’s installed in this building, suddenly you can see details," says Susan Hafenstein. “It’s like you just put your contacts in.”

Titan Krios microscope at Millennium Science Complex, photo by Nick Sloff '92 A&A
COMING INTO FOCUS: The Arctic (top) and Titan Krios (above) microscopes use high-speed cameras to image molecules of frozen samples down to the atomic level. Photo by Nick Sloff '92 A&A.

Hafenstein, director of the Center for Structural Biology, Huck Chair of Structural Virology and professor of biochemistry and molecular biology, leads the lab and works with faculty across campus. The lab’s first and largest microscope, the Titan Krios, suspends samples—up to 12 at a time—in liquid and then freezes them with liquid nitrogen to preserve the natural shape of the particles and arrest them mid movement.

There were roughly 100 cryo EM microscopes installed in universities in the United States over the last decade following the development of a direct electron detector, which provided higher resolution and image quality. What makes the Krios, an $8.5 million instrument that is one of only three of its kind in North America, different is its ability to perform a spectroscopy on a sample while it is being imaged, which allows researchers to see the structure of a particle and identify the chemical elements in it at the same time.

The Arctica microscope, purchased a few years later, also has full cryo EM capability. “At the time, [the Arctica] was considered a companion microscope for the Krios,” Hafenstein says. “But in using it, we found out that it’s much better than a companion; we collect data on it all the time now, too. People working on smaller particles—proteins, RNAs, smaller things—get better contrast with a microscope that has less accelerating voltage.”

The third microscope, the Talos C, has the ability to load samples in a single cell that allows particles to withstand even the vacuum of the microscope. 

Penn State researchers use the microscopes to see the nanoparticles they’ve developed for drug delivery directly interact with the cells, or study immune responses to certain viruses without having to focus on a specific antibody, instead looking at the response as a whole. “To make the technology available to all Penn State researchers was something of a passion of mine,” Hafenstein says.