Cryo-electron microscope to bring life sciences and materials sciences together

The FEI Titan/Krios transmission electron microscope, cryo-EM, can image structures down to the atomic level and can provide spectrographs of compounds and elements. Credit: Patrick Mansell

A new cryo-electron microscope, cryo-EM, that is also a spectrometer will bring life science methods together with materials science practices together to improve both fields and share methods across disciplines.

"The FEI Titan/Krios transmission electron microscope (TEM) operates at about -320 degrees Fahrenheit using liquid nitrogen. It is built to order and has a novel configuration that is the first of its type in the world," said Nigel Deighton, director of research instrumentation, Huck Institutes of the Life Sciences, Penn State. "It was built, not just for the usual user, which is a life scientist, but it enables spectroscopy as well."

Spectrographs look at the interaction of electromagnetic energy — infra-red, optical, ultraviolet or X-ray — with compounds and elements in materials. Cryo-EM looks at frozen samples and can see structures down to the atomic level. This method can produce 3-D images of biological molecules like DNA, proteins and viruses.

Right: The FEI Titan/Krios transmission electron microscope, cryo-EM, is both a microscope and a spectrometer. Life scientists and materials scientists are looking forward to sharing techniques and methods. Credit: Patrick Mansell

"We are proud to be making this significant investment to further the convergence of the physical and life sciences at Penn State," said Neil Sharkey, vice president for research. "Part of what pushes our research to the forefront is the ability for teams to collaborate and integrate knowledge and techniques across disciplines, continually learning from each other in both formal team settings and casual discussions. Our state-of-the-art instrumentation facilities in the Millennium Science Complex are themselves designed to support this dynamic kind of teamwork. The new Krios TEM adds to these capabilities and opens a whole a whole new realm of investigational possibilities."

Biologists, materials scientists and other researchers around Penn State and from outside the University will be able to use this new addition to the trove of common equipment available at Penn State.

"I want to understand viruses better and I study virus entry into the cell," said Susan Hafenstein, director of the cryo-EM facility, and associate professor of biochemistry and molecular biology and associate professor of medicine. "If we could stop entry, we can defeat them."

Hafenstein studies picornaviruses which have RNA genes so that every time they multiply they have mutations. This makes it hard to create vaccines and treatments because standard approaches are aiming at moving targets. If researchers can find parts of the virus that will not tolerate mutations, vaccines could target that part and be successful in preventing the diseases caused by these viruses.

"It is unusual to put a spectrometer on a life science microscope, but they have been used in materials science for a long time and enhance microscopic imaging with chemical information," said Bernd C. Kabius, senior scientist in the Materials Research Institute. "Using the instrument in scanning mode also can give element-specific contrast, separating lighter from heavier elements. There are a whole suite of materials science tools and methods we can use on tissue samples. There are also life science tools helpful for materials science, such as minimizing radiation damage."

While life scientists are looking forward to using this new microscope's spectrographic abilities, materials scientists are looking forward to exploring potential uses of the cryomicroscope in their work.

"The trend in materials science in the last one to two decades has been toward soft matter, nanoparticles and functionalizing bio-molecules for microelectronic applications," said Kabius. "These novel materials are as difficult to image as biological objects, which is why we now need the tools, which have been developed for the life sciences. Fifty years ago materials science was all hard materials, metals and ceramics. That has changed and is still changing. Now the emphasis is on soft materials like polymers and combinations of semiconductors with complex molecules for technological applications. Understanding catalytic reactions requires knowledge of the dynamic processes at surfaces in liquid environments, which are impossible to access with conventional methods. Cryo-EM can help by 'freezing' in intermediate states of these chemical reactions."

While materials science has a tool chest for hard materials, the life sciences already have a tool chest for soft and liquid materials.

Kabius suggests that these softer materials can be used for microelectronics applications and TV screens that roll up and travel. Other types of materials that could benefit from the microscope include catalysts and materials interfaces.

Regardless of the substance to be scanned, the samples need preparation. They are prepared in thin sections and go into the microscope frozen. The microscope has a feeder device to automate sample insertion.

To use the FEI Titan/Krios microscope, visit https://www.huck.psu.edu/content/instrumentation-facilities/cryo-electron-microscopy.

Microscopist Carol Bator examines samples from the FEI Titan/Krios transmission electron microscope at Penn State's Huck Institutes of the Life Sciences. Credit: Patrick Mansell

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