Once a crystal form of a particular drug candidate is available, it is critical to determine its crystal structure, as the structural information provides a solid foundation for further computational calculations and analytics on important physicochemical properties, including stability, solubility and moisture absorption. In addition, crystal structure information is fundamental in obtaining and defending polymorph patents, which require disclosure of the accurate structural information.
We are able to obtain structural information primarily by two experimental methods: microcrystal electron diffraction, or MicroED, and the traditional single X-ray diffraction (XRD). MicroED uses electron beams with shorter wavelengths than X-rays resulting in stronger diffraction pattern. As a small number of micrometer-sized crystal grains are adequate to generate a high-resolution electron diffraction pattern for the crystal structure analysis, MicroED lowers the requirements for the crystal sample in terms of shape, size and purity. In bypassing the time-consuming single-crystal preparation process, compared to the traditional XRD method, MicroED significantly improves the efficiency of crystal structure determination. Our MicroED platform also features an automated process that integrates sample loading, particle targeting, photograph, and on-the-fly monitor of data-collection progress capabilities. We are able to complete a structure determination project within two to three weeks.