single-crystal X-ray diffraction

Instead of grinding the sample up, single-crystal diffraction uses one small but well-formed crystal, roughly a tenth to a third of a millimetre across, glued to a thin fibre and mounted so it can be turned in the X-ray beam. As the crystal rotates, each family of atomic planes flashes out a sharp spot the instant it swings into the exact Bragg angle. Collect over many angles and you build a full three-dimensional constellation of spots — a direct photograph of the crystal's reciprocal lattice.

The power comes from that third dimension. Because the spots are separated in space rather than collapsed onto one axis, you can measure the intensity of thousands of individual reflections, each cleanly labelled by its own three integers (hkl). Each intensity gives the squared amplitude of the structure factor for that reflection. From this rich data set you recover (after solving the phase problem) the electron-density map, and from the map the exact positions of every atom, with bond lengths and angles to a few thousandths of an angstrom.

Single-crystal XRD is the gold standard for determining a crystal structure in full atomic detail, and it is how most small-molecule and protein structures are solved. The honest bottleneck is right there in the name: you need a single crystal of adequate size and quality, and coaxing one to grow can be the hardest part of the whole project. Some substances — many powders, coatings, and poorly crystallising materials — never yield a good single crystal, which is exactly when you fall back on powder methods or total-scattering (pair-distribution-function) analysis.