Real-Space Crystal Structure Analysis by Low-Dose Focal-Series TEM Imaging of Organic Materials with Near-Atomic Resolution.

Structural analysis of beam-sensitive materials by transmission electron microscopy (TEM) represents a significant challenge, as high-resolution TEM (HRTEM) requires high electron doses that limit its applicability to stable inorganic materials. Beam-sensitive materials, e.g., organic crystals, must be imaged under low dose conditions, leading to problematic contrast interpretation and loss of fine structural details. Here, HRTEM imaging of organic crystalline materials with near-atomic resolution of up to 1.6 Å is described, which enables real-space studies of crystal structures, as well as observation of co-existing polymorphs, crystal defects, and atoms. This is made possible by a low-dose focal-series reconstruction methodology, which provides HRTEM images where contrast reflects true object structure and can be performed on contemporary cryo-EM instruments available to many research institutions. Copper phthalocyanine (CuPc), a perchlorinated analogue of CuPc, and indigo crystalline films are imaged. In the case of indigo crystals, co-existing polymorphs and individual atoms (carbonyl oxygen) can be observed. In the case of CuPc, several polymorphs are observed, including a new one, for which the crystal structure is found based on direct in-focus imaging, accomplishing real-space crystal structure elucidation. Such direct analysis can be transformative for structure studies of organic materials.