High-Throughput Crystallization Screening Technique with Transmission PXRD Analysis

The ability to quickly generate and identify crystallinesolidsfor organic compounds in a parallel fashion requires a rapid, adaptablecrystallization screening strategy that delivers reliable, valuable,and consistent results. The key to the system is a standard platformsmall-scale (0.5-2 mg) crystallizer screening array that reproduciblycrystallizes compounds and facilitates the presentation of crystallizationsamples to both an automated polarized light microscope and an instrumentcapable of PXRD analysis. Data science technologies were leveragedto streamline the workflow of data visualization and processing. Thefully developed workflow successfully used both single-crystal andPXRD analyses to identify multiple polymorphs of a test compound ina single screening experiment on 200 mg of input material with commerciallyavailable crystallizers and instruments to perform a highly detailedcrystallization screening study. The methods and techniques describedherein are fully transferrable to those working in the synthetic organicchemistry field.

Automated summary

To quickly generate and identify crystalline solids for organic compounds, a rapid and adaptable crystallization screening strategy is needed. This study describes a system that utilizes a standard platform small-scale crystallizer screening array, automated polarized light microscope, and PXRD analysis instrument to deliver reliable and consistent results. Data science technologies are used to streamline data visualization and processing. The developed workflow successfully identifies multiple polymorphs of a test compound using single-crystal and PXRD analyses in a single screening experiment on 200 mg of input material.