Coherent diffraction imaging of single particles and biomolecules

Theory predicts that with an ultra-short and extremely bright coherent X-ray pulse, a single diffraction pattern may be recorded from a large macromolecule, a virus, or a cell before the sample explodes and turns into a plasma. The over-sampled diffraction pattern permits phase retrieval and hence structure determination.

X-ray lasers capable to deliver ultra bright and very short X-ray pulses for such experiments have recently started operations. Free-electron lasers are the most brilliant sources of X-rays to date, exceeding the peak brilliance of conventional synchrotrons by a factor of 10 billion, and improving. In the duration of a single flash, the beam focused to a micron-sized spot has the same power density as all the sunlight hitting the Earth, focused to a millimetre square. The interaction of an intense X-ray pulse with matter is profoundly different from that of an optical pulse. A necessary goal of the programme is to explore photon-material interactions in strong X-ray fields. Our aim in biology is to step beyond conventional damage limits and develop the science and technology required to enable high-resolution imaging of biological objects. Eligible targets include single virus particles, organelles, cells, nanocrystals, engineered nanoclusters and isolated macromolecules. The challenges engage an interdisciplinary approach, drawing upon structural sciences, biology, atomic and plasma physics, optics and mathematics. The potential for breakthrough science is great with impact not only in biology or physics but wherever dynamic structural information with high spatial and temporal resolution is valuable. The overall relevance of the programme extends beyond basic science, to technologies of essential importance to a future Europe.

A three-dimensional data set can be assembled from the diffraction patterns when copies of a reproducible sample are exposed to the beam one by one. The limiting factors are the accuracy of the orientation information, and heterogeneity in the sample population, both of which will blur the reconstructed image.