An advanced energy-filter on a H700H cryo-electron microscope is being assessed for digital imaging and analysis of biological structures at high sensitivity. The filter is equipped with a YAG-coupled, cooled, slow-scan CCD camera, and is entirely computer-controlled. The detective quantum efficiency of the CCD is greater than 0.7 for incident fluxes from 10 electrons per pixel to 10000 electrons per pixel. The low-intensity performance is improved relative to that of a cooled photodiode array because of its much lower read-out noise. The high-intensity performance is improved because the CCD images can be accurately gain-normalized. The normalization is made possible because the small pixels of the CCD (24 microns square) are smaller than the typical spatial variation of the incoming signal. It has been demonstrated that spectra can be acquired in the normal mode that contain as many as 100 million fast electrons per channel, corresponding to statistics at the 0.01% level. This is expected to reduce detection limits for elemental analysis of biological specimens to a point that is even lower than can be achieved with a photodiode array detector. The use of the imaging filter is also being explored for the acquisition of low-dose micrographs of beam-sensitive specimens.
