Microfluidics for high-throughput screening and optimisation of nucleation and growth kinetics of crystals

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Crystallisation is one of the key unit operations used in the Pharmaceutical, Food, Agrochemical and Particulates industries. The physical properties of a crystal including solubility, rate of dissolution, and growth and nucleation kinetics govern its potential applications, and production at an industrial scale. These parameters also strongly depend on the solvent/ solvent mixtures used, temperature and hydrodynamics. Multiple experiments need to be performed to determine the crystal properties and relevant crystallisation data, making it a slow and laborious process. This project will develop a novel and versatile next-generation high-throughput platform for rapid and precise characterization of key physical and kinetic properties of crystals. The system is also suitable for screening polymorphs by achieving accurate temperature control to identify polymorphic forms of crystals. Several approaches involving micro and milli fluidic flow systems, static arrays of droplets and small volume arrays will be explored to evaluate optimal process conditions - solvents, droplet size and temperatures. The platform will be designed such that it can be used with multiple solvents and temperatures, that solutions can be automatically dispensed and mixed, and that continuous detection can be achieved. Different analytical techniques including XRD and Raman will be integrated into the platform to measure growth and dissolution rates. Image analysis techniques will be developed for rapid analysis of the image-based crystallisation data obtained using microscopy techniques. Handling massive data is a challenge and this will be addressed by generating automated digital image analysis algorithms that can enable rapid and accurate analysis of large datasets.