Large-Format Direct Detection Camera for Cryo-EM at 100 Kev

Imaging vitrified biological samples at 100 keV has been shown to provide more signal-to-noise per unit damage as compared to 200 or 300 keV 1-2 . In addition to a better image per unit damage, screening samples at lower keV offers an economical solution due to the higher accessibility of 100 keV transmission electron microscopes (TEMs). Direct detection sensors provide the highest DQE and have been a key contributor to the resolution revolution in cryo electron microscopy (cryoEM). Unfortunately to date, direct detection cameras have been primarily optimized to work at high accelerating voltages (200 - 300 kV) and low accelerating voltages (5 – 80 kV) so there remains a gap in direct detection technologies targeting 100 kV 1-2 . Through a major shift in detector design, we have for the first time realized a sensor that performs optimally at 100 kV. The performance of this sensor at 100 kV is comparable to the best performance of existing monolithic active pixel and hybrid pixel arrays working in their respective optimal energy ranges, and it simultaneously provides a large number of pixels (2304 x 3240). This new direct detection sensor optimized for imaging at 100keV is expected to have significant implications for the field of cryo-electron microscopy (cryo-EM) in the push for a low-cost cryo-EM microscope. Recent efforts in using cryo-EM at 100 keV have demonstrated the feasibility of achieving high-resolution protein structures using single particle reconstruction 1 . These studies have also noted the lack of a suitable