An assessment of the resolution limitation due to radiation-damage in X-ray diffraction microscopy

X-ray diffraction microscopy (XDM) is a new form of X-ray imaging that is being practiced at several third-generation synchrotron-radiation X-ray facilities. Nine years have elapsed since the technique was first introduced and it has made rapid progress in demonstrating high-resolution three-dimensional imaging and promises few-nanometer resolution with much larger samples than can be imaged in the transmission electron microscope. Both life- and materials-science applications of XDM are intended, and it is expected that the principal limitation to resolution will be radiation damage for life science and the coherent power of available X-ray sources for material science. In this paper we address the question of the role of radiation damage. We use a statistical analysis based on the so-called dose fractionation theorem of Hegerl and Hoppe to calculate the dose needed to make an image of a single life-science sample by XDM with a given resolution. We find that the needed dose scales with the inverse fourth power of the resolution and present experimental evidence to support this finding. To determine the maximum tolerable dose we have assembled a number of data taken from the literature plus some measurements of our own which cover ranges of resolution that are not well covered otherwise. The conclusion of this study is that, based on the natural contrast between protein and water and Rose-criterion image quality, one should be able to image a frozen-hydrated biological sample using XDM at a resolution of about 10 nm. (C) 2008 Elsevier B.V. All rights reserved.