Breaking the 1-μm Barrier with the Electron Diffractometer XtaLAB Synergy-ED

3D electron diffraction enables crystal structure determination from crystals that are smaller than approximately 1 μm, a size at which conventional single-crystal X-ray diffraction often becomes impractical. Because electrons interact much more strongly with matter than X-rays, nanometer-scale crystals can produce diffraction patterns suitable for structural analysis. This significantly expands the range of materials that can be characterized, including compounds that cannot be grown into larger crystals.

A dedicated electron diffractometer is optimized specifically for diffraction rather than high-resolution imaging. Its electron optics minimize adjustments when switching between imaging and diffraction modes, while integrated software automates instrument control, data collection, processing, and structure solution. This reduces the amount of specialized electron microscopy expertise required and allows crystallographers to perform measurements using a workflow similar to conventional single-crystal X-ray diffraction.

Sample preparation is straightforward and typically requires less than 1 mg of material. Fine crystals are dispersed onto an electron microscopy grid, and larger crystals can be gently crushed to reduce their thickness. For poorly crystalline materials, dissolving the sample and recrystallizing it directly on the grid may improve crystal quality. The most important consideration is crystal thickness, which should generally remain below 1 μm and may need to be substantially thinner for heavier inorganic materials.

Yes. The technique has been successfully applied to organic compounds, organometallic complexes, and inorganic materials. Results from more than one hundred analyzed structures demonstrate that it is broadly applicable across diverse chemistries and crystal systems, making it useful in pharmaceutical, chemical, and materials research.

Electron diffraction data are more strongly affected by multiple scattering because electrons interact much more strongly with matter than X-rays. Conventional refinement methods often assume kinematic scattering, which does not fully account for these effects, resulting in higher refinement residuals. Even so, the resulting structural models are generally accurate enough for reliable crystal structure determination, and ongoing improvements in refinement methods are expected to further improve data quality.

Individual microcrystals within a heterogeneous sample can be analyzed separately, allowing minor crystalline components to be identified even when they are present in very small quantities. This makes electron diffraction valuable for investigating degradation products, contaminants, or unexpected phases that may not be apparent using bulk analytical techniques. Only a small amount of material is required for analysis.

Electron diffraction can distinguish different crystalline polymorphs by determining their unique crystal structures and unit cell parameters. Because measurements require only nanocrystals and very small sample quantities, polymorph screening can be performed rapidly, even when only limited material is available. This capability is particularly valuable in pharmaceutical development and advanced materials research, where crystal form can significantly influence material properties and performance.