Flow-Xl: A New UK Facility for Analysis of Crystallisation in Flow Systems

Crystalline materials are everywhere. They are abundant in nature (eg bones and seashells) and in the environment (eg. rocks and ice) and are found across a diverse selection of everyday products including pharmaceuticals, batteries and food. Crystallisation can also be undesirable, such as in the formation of kidney stones or scale in a kettle. The ability to control crystallisation processes - to generate particles with specific sizes, shapes and structures, and to control where and when crystallisation occurs - therefore promises huge benefits to society. Here, we need to develop strategies to prevent crystallisation. All of these goals can only be achieved by developing a robust understanding of the mechanisms that underlie crystal nucleation and growth.

This project will create a new UK, and indeed world-first research facility - Flow-Xl - that can address this challenge. Flow-Xl will be located at the University of Leeds and will enable in situ, time-resolved characterisation of crystallisation processes in highly controlled environments. This will be achieved by coupling X-ray diffraction and Raman spectroscopy to a range of fully-integrated flow platforms. These analytical techniques will be used simultaneously to study crystallisation pathways from amorphous and poorly crystalline precursor materials, through crystalline intermediates, to the ultimate crystal products. This combined capability is not currently available anywhere else in the world.

Flow-Xl is also extremely timely, where it is only possible because top-of-the-range laboratory X-ray instruments are now so good that they can replace synchrotrons for many experiments. Parallel innovative data processing and analysis methods will be developed and provided for Flow-Xl users, building on our key breakthrough methodology. These will allow the maximum information to be obtained from Flow-Xl experiments.

The use of flow systems is also critical to our technique, and Flow-Xl will offer a number of contrasting flow platforms. The simplest of all is continuous flow, which mimics many industrial manufacturing processes. Many industrial crystallisation processes also take place in stirred vessels, and these environments will be studied by withdrawing solution from a batch reactor through a flow loop for analysis. Finally, it will be possible to study crystallisation in segmented flow, where individual droplets provide highly reproducible reaction environments that are ideally suited to fundamental studies of crystallisation mechanisms. Flow-Xl will also enable us to share our expertise in the manufacture of flow-cells for X-ray measurements with the entire UK research community.

Flow-Xl will be operated as a multi-user facility that is open to all academic and industrial researchers across the UK, and will be supported by an experienced research officer. This will allow the equipment to be fully utilised for a wide range of projects spanning industrial processes through to developing fundamental understanding. In addition to providing a cutting-edge, stand-alone research facility, Flow-Xl will also support Diamond Light Source and its users by providing an alternative or precursor to synchrotron time for many experiments. This frees-up precious beam-time for experiments that really need it, and enables researchers to conduct screening/ feasibility experiments prior to their beam-time.

The facility will support a range of existing projects including the formation of organic framework compounds, biomineralisation and bio-inspired crystallisation, fouling, materials discovery, production of single enantiomer crystals, polymorph selection and the development of artificial intelligence in modelling of crystallisation. By building a strong user community from academia and industry over the course of the project, we will ensure this powerful new facility finds application across a wide range of scientific programmes.

We will establish a unique, laboratory-based facility (Flow-Xl) for in situ X-ray diffraction and Raman study of crystallisation and materials assembly processes under flow conditions. Flow-Xl will provide researchers from academia and industry with a new capability, allowing them to analyse crystallisation and assembly processes in situ with excellent time resolution and definition of reaction conditions. While the need to characterise crystallisation mechanisms is central to virtually every study of crystallisation phenomena, it remains a significant challenge.

Contributions to the Knowledge Base
The state-of-art equipment will provide the community with a new experimental capability that will contribute to the fundamental knowledge base across a wide range of disciplines (chemistry, pharma, materials, food) through high impact papers, presentations at key international conferences, seminars and our focused user events.

Collaboration and Network Activities
The facility will offer support and access for a broad user-base interested in the discovery, development and application of crystallisation methods across the fine chemical, pharmaceutical and materials sectors. The research enabled by Flow-Xl will be exploited by collaboration with a range of critical mass research and community networks. These include the CMAC Manufacturing Hub, UK Catalysis Hub, Centre for Sustainable Chemical Technologies, Centre for Sustainable Chemistry, the Materials Innovation Factory, the Royce Institute, the Leeds Institute for Process Research and Development (iPRD), Diamond Light Source and the Directed Assembly Network. In particular, Flow-Xl will complement experimental opportunities at Diamond, and we will work in partnership with them to ensure opportunities are maximised.

User Engagement and Training
Flow-Xl will be operated with a user-focused model; our goal is to create a vibrant academic and industrial user community. Extensive support will be provided by an experienced research officer, and researcher training will include the use of flow platforms, diffraction and Raman techniques and analysis of multi-variate data. Flow-Xl will therefore offer valuable training for the next generation of chemists, physicists, engineers and materials scientists who need to control crystallisation or materials assembly for functional materials, supramolecular chemistry, crystal and particle engineering and sustainable manufacturing. Engagement via access visits, applications support and user meetings will ensure that users are able to benefit from developments in experimental approaches, to carry out new experiments and adapt flow systems to meet their research needs. This ambitious and varied project also provides an exceptional training opportunity for a postdoctoral researcher.

Economic and Societal Benefit
Flow-Xl provides excellent opportunities for economic benefit via engagement with industry. It will support existing industries and open up new opportunities for growth in areas including food, fine chemicals and pharmaceuticals by enabling characterisation and optimisation of crystallisation processes. Continuous processing is attracting increasing attention, but is hindered through a lack of in situ XRD characterisation. Flow-Xl will therefore contribute to the economy by delivering manufacturing-related research, increasing the competitiveness of advanced process manufacturing by developing new, agile, cost-effective processes and creating innovative products through new technologies. Our network of industry users includes leading pharmaceutical manufacturers AZ, Bayer, GSK, Lilly, Novartis, Pfizer, Roche, Takeda and agrichemical manufacturer Syngenta; we will grow this network over the award.

We will deliver public engagement via a dedicated website and articles, various events such as Science cafes and through the STEM Ambassador programme, using examples and demonstrators to inspire the next generation of researchers