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

Lead Research Organisation: University of Leeds
Department Name: Chemical and Process Engineering

Abstract

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.

Planned Impact

The CDT in Molecules to Product has the potential to make a real impact as a consequence of the transformative nature of the underpinning 'design and supply' paradigm. Through the exploitation of the generated scientific knowledge, a new approach to the product development lifecycle will be developed. This know-how will impact significantly on productivity, consistency and performance within the speciality chemicals, home and personal care (HPC), fast moving consumer goods (FMCG), food and beverage, and pharma/biopharma sectors.
UK manufacturing is facing a major challenge from competitor countries such as China that are not constrained by fixed manufacturing assets, consequently they can make products more efficiently and at significantly lower operational costs. For example, the biggest competition for some well recognised 'high-end' brands is from 'own-brand' products (simple formulations that are significantly cheaper). For UK companies to compete in the global market, there is a real need to differentiate themselves from the low-cost competition, hence the need for uncopiable or IP protected, enhanced product performance, higher productivity and greater consistency. The CDT is well placed to contribute to addressing this shift in focus though its research activities, with the PGR students serving as ambassadors for this change. The CDT will thus contribute to the sustainability of UK manufacturing and economic prosperity.
The route to ensuring industry will benefit from the 'paradigm' is through the PGR students who will be highly employable as a result of their unique skills-set. This is a result of the CDT research and training programme addressing a major gap identified by industry during the co-creation of the CDT. Resulting absorptive capacity is thus significant. In addition to their core skills, the PGR students will learn new ones enabling them to work across disciplinary boundaries with a detailed understanding of the chemicals-continuum. Importantly, they will also be trained in innovation and enterprise enabling them to challenge the current status quo of 'development and manufacture' and become future leaders.
The outputs of the research projects will be collated into a structured database. This will significantly increase the impact and reach of the research, as well as ensuring the CDT outputs have a long-term transformative effect. Through this route, the industrial partners will benefit from the knowledge generated from across the totality of the product development lifecycle. The database will additionally provide the foundations from which 'benchmark processes' are tackled demonstrating the benefits of the new approach to transitioning from molecules to product.
The impact of the CDT training will be significantly wider than the CDT itself. By offering modules as Continuing Professional Development courses to industry, current employees in chemical-related sectors will have the opportunity to up-skill in new and emerging areas. The modules will also be made available to other CDTs, will serve as part of company graduate programmes and contribute to further learning opportunities for those seeking professional accreditation as Chartered Chemical Engineers.
The CDT, through public engagement activities, will serve as a platform to raise awareness of the scientific and technical challenges that underpin many of the items they rely on in daily life. For example, fast moving consumer goods including laundry products, toiletries, greener herbicides, over-the-counter drugs and processed foods. Activities will include public debates and local and national STEM events. All events will have two-way engagement to encourage the general public to think what the research could mean for them. Additionally these activities will provide the opportunity to dispel the myths around STEM in terms of career opportunities and to promote it as an activity to be embraced by all thereby contributing to the ED&I agenda.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S022473/1 31/03/2019 29/09/2027
2746418 Studentship EP/S022473/1 30/09/2022 29/04/2027 Ashmita Kadam