Controlling the polymorph (crystal structure) of crystalline materials is of vital importance to both material science and the pharmaceutical industry. Many crystal polymorphs are difficult to access, however, as polymorph is determined by both kinetics and thermodynamics. Recently, it has been observed that precipitation of crystals in confinement often leads to the formation of unusual polymorphs. For example, CaCO3 forms purely as aragonite when it is precipitated in small nanopores. These observations suggest that confinement could offer a generic route to polymorph control. However, the fundamental mechanisms underlying this confinement effect are poorly understood. In this project, Dr. Yifei Xu uses in-situ transmission electron microscopy (TEM) to study how confinement effects give rise to polymorph control. CaCO3 forms the principal focus of the study, and a graphene pocket (GP) is used as the confinement system. We expect the study to not only advance our knowledge of crystal polymorphism, but also pave the way for rationally using confinement to control crystal polymorph in industry and lower down the cost of relevant products such as Ritonavir. By the end of this project, we have confirmed that GP can significantly control the polymorph of CaCO3. Using in-situ TEM in combination with other techniques, we have performed 3D high-resolution observation of the crystal nucleation processes in GP, and figured out the underlying mechanisms. Furthermore, we discovered that the GP can control the polymorph of several other crystals as well, indicating its potential for industrial applications.
