Pixel detectors for high-resolution cryo-electron microscopy

The application of electronic detectors to cryo-electron microscopy is discussed in this paper with special reference to hybrid silicon pixel detectors. During the past decade, phosphor-fibre optics CCD detectors have proved quite adequate for some of the biological applications. However, it has become increasingly clear that, in more demanding applications, it will be necessary to use a different approach in which the intermediate step of energy conversion to light in the phosphor is eliminated. Direct detection in hybrid silicon pixel detectors offers the potential for excellent spatial resolution, rapid readout and high quantum efficiency. In this paper we discuss this approach and also some problematic issues, viz. radiation tolerance, size of detector, etc. and suggest the minimum specifications for a detector, which would be useful for both electron diffraction and high-resolution single-particle imaging. An evaluation of Medipix1 (designed by the Medipix collaboration) for electron microscopy has been published recently. We demonstrate the usefulness of Medipix1-like detectors for a number of electron diffraction patterns from inorganic and biological specimen. Finally, there is a brief discussion of future developments beyond single-chip imaging.