Image-Analysis-Based Method for 3D Crystal Morphology Measurement and Polymorph Identification Using Confocal Microscopy

A new technique for the measurement of 3D crystal morphology and identification of its polymorph using tomographic images is proposed. Confocal microscopy is used for the first time to obtain tomographic images of crystals that are coated with a suitable fluorescent dye. A convex polyhedron is fitted through a stack of tomographic images of a crystal to obtain the normal vectors of each facet and their corresponding perpendicular distances from the center of the crystal. The angular patterns are generated from the measured normal vectors and are matched with the master angular patterns of each polymorph. It is shown that the matching of the angular patterns is unique and provides a simpler way to identify polymorphs. An image-analysis program that can be integrated with conventional confocal microscopes was created to sequentially perform image processing, morphology measurement, and polymorph detection. This program was used to measure morphologies and identify polymorphs of 2D and 3D acetaminophen crystals. Detailed directions are provided to enable the application of the methodology without the need for specialpurpose software. The image-analysis program is also suitable for repeated measurements to produce morphology distributions. This technique will provide an effective platform for measuring the 3D shapes of materials of interest to many applications.