Direct methods for solving the phase problem were invented in the mid-1950s, got a Nobel in 1985 and have now been replaced almost completely by dual-space phase retrieval algorithms, such as charge flipping. Although crystals are still rotated in the beam of probing radiation as they were 100 years ago, this is no longer done by hand, but under complete computer control. In a nutshell: radiation sources have developed from homemade X-ray tubes to highly intense and tunable synchrotrons, X-ray free electron lasers (XFEL) and ultrafast electron diffractometers signal observation evolved from photographic film to energy-discriminating electronic detectors. This phenomenal achievement is due to several generations of pioneering crystallographers taking advantage of a variety of technical advances.
Since the Braggs determined the first crystal structures ca 100 years ago, single-crystal X-ray structure determination has become so well understood that both the acquisition and the interpretation of the diffraction data are now largely automated and make it the analytical method of choice for the characterization of the chemical composition and the three-dimensional (3D) structure of most newly synthesized chemical compounds.
