Report on a project on three-dimensional imaging of the biological cell by single-particle X-ray diffraction.

Single-particle X-ray diffraction is an extension of X-ray crystallography which allows the specimen to be any small solid-state bounded object; in Shapiro et al. [Proc. Natl Acad. Sci. USA (2005), 102, 15343-15346] and Thibault et al. [Acta Cryst. (2006), A62, 248-261], the reader can find descriptions of a recent StonyBrook/Berkeley/Cornell two-dimensional imaging of a yeast cell by this technique. Our present work is aimed at extending the technique to the three-dimensional imaging of a cell. However, the usual method of doing that, namely rotating the specimen into many orientations in the X-ray beam, has not as yet given sufficiently good three-dimensional diffraction data to allow the work to go forward, the largest problem being the difficulty of preventing unwanted levels of change in the specimen through the extended exposure to a hostile environment of X-rays and, in some cases, high vacuum and/or extreme cold. The present paper discusses possible methods of dealing with this problem.