Abstract

X-ray free-electron lasers (FELs) are very large machines that produce the briefest and most intense flashes of X-rays. The X-ray beam at the world’s first hard X-ray FEL , the Linac Coherent Light Source in Stanford, is so intense that it melts a hole through 3 mm of stainless steel in under a second. Yet we apply this beam to elucidate the molecular structure of proteins and obtain images of virus particles, which are certainly more delicate than steel. In fact, these objects are completely vaporised in the beam, and we overcome the problem of this radiation damage by using the short X-ray pulses to outrun the explosion. We have shown that we obtain atomic-resolution information with pulses of 30 fs or shorter. This “diffraction before destruction” technique allows us to determine the molecular structures of proteins that cannot be grown into large enough crystals or are too radiation sensitive for conventional X-ray crystallography with synchrotron radiation. We aim to push this technique to smaller and smaller samples—all the way down to the single molecule.