Extending the methodology of X-ray crystallography to allow imaging of micrometre-sized non-crystalline specimens

The contrast and penetrating power afforded by soft X-rays when they intera ct with matter makes this form of radiation ideal for studying micrometre-s ized objects(1,2). But although soft X-rays are useful for probing detail t oo fine for visible light microscopy in specimens too thick for electron mi croscopy, the highest-resolution applications of X-ray imaging have been tr aditionally limited to crystalline samples. Here we demonstrate imaging (at similar to 75 nm resolution) of a non-crystalline sample, consisting of an array of gold dots, by measuring the soft X-ray diffraction pattern from w hich an image can be reconstructed. The crystallographic phase problem(3)-t he usually unavoidable loss of phase information in the diffraction intensi ty-is overcome by oversampling(4) the diffraction pattern, and the image is obtained using an iterative algorithm(5). Our X-ray microscopy technique r equires no high-resolution X-ray optical elements or detectors. We believe that resolutions of 10-20 nm should be achievable; this would provide an im aging resolution about 100 times lower than that attainable with convention al X-ray crystallography, but our method is applicable to structures roughl y 100 times larger. This latter feature may facilitate the imaging of small whole cells or large subcellular structures in cell biology.