Forgotten facility transformed into microscopy center

The Advanced Electron Microscopy facility houses four powerful electron microscopes that can image everything from tissues to atoms.

The Advanced Electron Microscopy (AEM) facility is a shared resource of the BSD, managed by the Office of Shared Research Facilities (OSRF). First developed by Ernst Ruska in the 1930’s, the principles of electron microscopy (EM) are very similar to light microscopy (LM), but instead of using photons and glass lenses, electrons are accelerated through a vacuum and electromagnetic lenses focus them onto biological samples, allowing researchers to collect images of proteins, cells, and tissues.

Even though EM historically has been foundational in both cell biology and structural biology, it took many decades of developments for Ruska’s original vison to be completely realized. In 2017, the Nobel prize in Chemistry was awarded for the development of cryo-EM, which involves flash-freezing solutions before imaging (this technology was recently used in the world-wide effort to determine the COVID virus’s spike protein). This kick-started the “Resolution Revolution” with increasingly powerful microscopes, which UChicago quickly joined as well.

In 2017, the University already had an EM facility dedicated to cryo-preservation and 3D tomography in the sub-basement of the Gordon Center for Integrative Science, but the facility needed additional space to accommodate a new 12-foot tall cryo-EM called the Titan Krios. The EM facility team went on a search for space across campus, discovering a new research home while unearthing an interesting bit of history in the Franklin McLean Institute (FMI).

The FMI building was originally built in 1953 and was known as Argonne Cancer Research Hospital until 1973. It was one of the first institutions equipped to use radiation sources for studying of cancer, and housed the university’s original cyclotron, a type of particle accelerator that produces radioactive isotopes that can be used for imaging procedures, installed in 1968.

After the cyclotron and other equipment in the Cancer Research Hospital was decommissioned in the 1990s, the space was converted to offices, and it would have stayed that way if not for the need to find a home for the Titan Krios. In 2018, construction of the new AEM facility started by fully gutting the space and partially removing a 3-foot-thick concrete, lead, and iron wall that had been shielding for a linear accelerator. The newly created space not only had room for the Titan Krios, but also three other EMs, an operator’s room, two offices, and a mezzanine level with supporting equipment necessary for all the scopes.

The facility now houses four EMs:

  1. The Titan Krios, suited for cryo-EM studies operating at around -300°F (-196°C) and used to view the structure of individual proteins and 3-dimensional cellular volumes at angstrom resolutions;
  2. The Aquilos, which also operates at cryo temperatures but has two beams: an electron beam for imaging, and an ion-beam (fires Gallium atoms to ablate and thin the sample) which can be used to cut windows into cells to be imaged on the Titan Krios, revealing proteins in their native cellular context;
  3. The Volumescope, which allows researchers to investigate the complex 3-dimensional organization (cellular connectomics) of cells and tissues at nanometer resolution;
  4. The Glacios, a cryo-EM installed in 2022 that can be used for high-speed sample screening­ to identify samples ready for data collection on the Krios. The Glacios will also be used for cryo-micro electron diffraction (mirco-ED), which can determine the structure of chemical compounds at atomic resolution.

These four new EMs give researchers the ability to take any given biological problem and analyze it “Google Earth”-style, zooming in from a large volume of tissue to visualize intracellular compartments and ultimately getting the structures of specific macromolecular components of the cells at Angstrom resolutions. This information can lead to a better understanding of complex cell functions, provide clues explaining cellular mechanisms, insights into cellular aberrations, and drug discoveries that can guide researchers to novel treatments and cures for diseases.

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