Rapid Screening of Calcium Carbonate Precipitation in the Presence of Amino Acids: Kinetics, Structure, and Composition

Soluble additives are widely used to control crystallization, leading to a definition of properties including size, morphology, polymorph, and composition. However, because of the number of potential variables in these experiments, it is typically extremely difficult to identify reaction conditions-as defined by solution compositions, temperatures, and combinations of additives-that give the desired product. This article introduces a high-throughput methodology which addresses this challenge and enables the streamlined preparation and characterization of crystalline materials. Using calcium carbonate precipitated in the presence of selected amino acids as a model system, we use well plates as microvolume crystallizers, and an accurate liquid-handling pipetting workstation for sample preparation. Following changes in the solution turbidity using a plate reader delivers information about the reaction kinetics, while semiautomated scanning electron microscopy, powder X-ray diffraction, and Raman microscopy provide structural information about the library of crystalline products. Of particular interest for the CaCO3 system is the development of fluorescence-based protocols which rapidly evaluate the amounts of the additives occluded within the crystals. Together, these methods provide a strategy for efficiently screening a broad reaction space, where this can both accelerate the ability to generate crystalline materials with target properties and develop our understanding of additive-directed crystallization.