Pioneering work by scientists at the Molecular Foundry played a key role in the 2017 Nobel Prize in chemistry, awarded today, honoring the development of cryo-electron microscopy, or cryo-EM, an imaging technique that has launched the fields of structural biology and biochemistry into an exciting new era of discovery.
In the scientific background detailing the development of cryo-EM, the Nobel committee highlighted “critical developments” that made it possible to take full advantage of the Nobel laureates’ achievements.
One development was freezing samples to protect them from the damage of intense electron beams. However, to minimize damage to the sample, only a few electrons are used to image biological macromolecules, creating “noisy” images. The use of averaging is meant to deal with that “noise,” but it requires the samples to be precisely aligned. That created a serious bottleneck when managing tens to hundreds of thousands of images.
Enter the revolution enabled by direct detector technology that was developed at the National Center for Electron Microscopy (NCEM) facility at the Molecular Foundry as part of the Transmission Electron Aberration-corrected Microscope (TEAM) project. TEAM was a multi-facility development project to integrate the latest advancements in electron optics, detectors, sample stages, and computational techniques into a suite of instruments freely available to the worldwide scientific community.
The new detector was developed for the TEAM project by Berkeley Lab scientist Peter Denes who had been developing detectors based on complementary metal oxide semiconductors (CMOS) technology for applications in materials science. The work allowed for direct detection of electrons, which directly hit pixel sensors in a thin layer of silicon. The state-of-the-art approach allowed for the direct “counting” of electrons and essentially eliminated the problem of noise.
Rather than take a single picture for each sample, the direct detector camera shoots multiple frames that are then put together to create a high-resolution image. The technology has been compared to the process of recording a movie, and it effectively eliminates the problem of blur or noise when the sample moves. Because the technology was initially designed for applications in materials science, it had to be fast to catch the movement of atoms and reveal how defects spread
The Nobel committee specifically noted the advantage in speed as well as the improved signal-to-noise ratio and spatial resolution in this new generation of detectors.