Purpose-built electron cryo-microscope running at 100 keV promises to reduce the cost and complexity for biological structure studies
Though electron cryo-microscopy (cryo-EM) has proved itself an invaluable technique to obtain detailed atomic structures of biological materials, technological advancements have steadily propelled its costs upwards. Current state-of-the-art microscopes now cost several million pounds, precluding many researchers and institutes from using the beneficial approach and ultimately slowing down progress towards molecular discoveries. To combat this, Chris Russo’s group and Richard Henderson, both in the LMB’s Structural Studies Division, have worked with a team across the LMB and other collaborators to build a new microscope at a fraction of the size and costs of current suppliers.
The spiralling costs of electron microscopes are largely down to the systematic rise in electron energies to combat issues such as poor electron detector efficiency, low source brightness, ice contamination, and more. However, previous research from Chris’ group has illustrated that 100 thousand electron volts (keV) is actually the optimum energy for imaging – three times lower than the current most popular energy of 300 keV.
Spearheaded by Greg McMullan, and assisted by the LMB’s Scientific Computing Facility, Electronics and Mechanical Workshops, and Shaoxia Chen and Giuseppe Cannone from the LMB’s Electron Microscope Facility, the team built a new electron microscope, eschewing some of the recent microscope additions which drive up cost. The new microscope features several bespoke features designed to optimise structure determination at a lower energy, including a new 100 keV field emission gun, a low aberration objective lens with cryobox, and a new high-speed, high-efficiency electron detector.
To prove its capabilities, a team of researchers including Ph.D. students Katerina Naydenova, Josh Dickerson and Daniel Mihaylov and postdocs Mathew Peet and Hugh Wilson, used the new microscope to determine eleven atomic structures. The macromolecular specimens chosen were a diverse selection, with varying sizes and symmetries, and a range of subunit numbers from one to sixty. Notably, each were solved with a fraction of the data normally required, with each structure being obtained after a single day of data collection.
This new electron microscope promises to significantly increase the accessibility of cryo-EM. Not only does the microscope cost up to ten times less than current high-end models – whilst delivering the same results for single particle cryo-EM – the additional costs of establishing a microscopy room are also reduced tenfold and running costs are just 5% of current levels. Ultimately, this will encourage faster scientific progress, allowing research laboratories around the world to access quick, simple and reliable cryo-EM – a key technique for many scientific studies, including the process of developing new drugs.
This breakthrough builds on the LMB’s long history at the forefront of cryo-EM development; from using electron microscopy to determine the structure of 2-D crystals of the membrane protein bacteriorhodopsin in the 1970s, to the adoption and development of cryo-EM in the 1980s and 1990s, and the more recent achievement of atomic resolutions and the development of new computer software to better process the data generated by the technique.
This work was funded by UKRI MRC, UKRI BBSRC, UKRI Innovate UK, the Wellcome Trust, UKRI EPSRC, Astex Pharmaceuticals Sustaining Innovation postdoctoral fellowship and a Herchel Smith fellowship.
Structure determination by cryoEM at 100 keV. McMullan, G., Naydenova, K., Mihaylov, D., Yamashita, K., Peet, MJ., Wilson, H., Dickerson, JL., Chen, S., Cannone, G., Lee, Y., Hutchings, KA., Gittins, O., Sobhy, MA., Wells, T., El-Gomati, MM., Dalby, J., Meffert, M., Schulze-Briese, C., Henderson, R., Russo, CJ. PNAS
Chris’ group page
Richard’s group page
Scientific collaboration to focus on search for new, improved detectors for low energy cryo-EM
Looking at Molecules: The electron cryo-microscopy revolution at the MRC LMB
100keV vacuum sealed field emission gun for high resolution electron microscopy. El-Gomati, MM., Wells, T., Zha, X., Sykes, R., Russo, CJ., Henderson, R., McMullan, G. Journal of Vacuum Science & Technology B (2021)
Cheaper microscope could bring protein mapping technique to the masses, Science News
Microscope reduced in size and running cost, UKRI News
A low-cost electron microscope maps proteins at speed, Nature News