Development of a Flexible Flow System for the Synthesis of Macro and Nanocrystals

Crystal properties such as size, purity, structure, and habit have a considerable impact on a crystals physiochemical properties and subsequent performance in specific applications harnessing the ability to rapidly synthesise bespoke crystals is extremely important in several chemical industries. Continuous cooling crystallisation emerge as an environmentally conscious alternative to traditional batch crystallisation capable of facilitating rapid in-situ process analytical techniques (PATs). Continuous crystallisation has limitations this project will look to address these areas through detailed process & computational optimisation, with the intention of finding the non-dominated solution between conflicting sustainability and crystal property performance objectives.This project will have a significant impact on the Sustainable Development Goals, 9 (Industry, Innovation and Infrastructure),12(Responsible Consumption and Production),13(Climate Action) by improving on the sustainability aspect of pre-existing crystallisers through reduced costs, material utilization and energy usage with enhanced waste minimisation. This research contributes to several UK Net Zero Research & Innovation Challenges-'Developing digital solutions and unlocking resource and energy efficiency' through the use of multi-variable, multi-objective Bayesian algorithms in flow crystallisation. This will completely negate human induced errors, increase safety and screening throughput but would also see a huge leap in mechanistic understanding of the nucleation and growth in crystallisation. Vanillin (macroscale) and Caesium Lead Halide Perovskites (nanoscale) have been selected as widely referenced model examples of cooling crystallisation, which will be delivered through tri-segmented flow and an iteration of the kinetically regulated automated input crystalliser (KRAIC). Process Optimisation will begin with evaluating the reagents that define tri-segmented flow to determine the compromise between sustainability, product yield and segmentation regularity. The physical arrangement of utility and process streams will be evaluated to investigate the impact on product yield while also looking for opportunities to recycle and remove streams to aid with process waste minimisation. Core hardware items will be optimised systematically using rapid techniques such as Additive Manufacturing (AM), improving on sustainability aspects based on material choice and process efficiency while increasing product yield. Probes will be implemented to monitor process variables In-situ along with PATs such as UV-Vis spectroscopy which will be implemented at macroscale to provide rapid compositional information, & coupled with Photoluminescence Spectroscopy provides information on particle concentration, shape, and size at nanoscale. Supplementary compositional information and detailed structural information will be uncovered using single crystal (SC-XRD) & powder (PXRD) x-ray diffraction techniques. Performed using ex-situ equipment at the University of Nottingham & in-situ equipment at national facilities such as Flow-Xl at the University of Leeds, and Diamond Light Source. Computational optimisation begins with extracting data from in-situ PATs & converting it into a format that is suitable for manipulation by python-based machine learning algorithms. The multi-variable algorithms will be responsible for receiving user defined inputs and in-situ process data, & formulating an informed output that will manipulate process inputs to reach what will initially be a single objective (morphology), before progressing to finding the group of non-dominated solutions (pareto front) between multiple conflicting objectives. Both platforms have been created with the intention of being applied to flow crystallisation outside of my chosen models assessing whether my macro & nanoscale systems are applicable to the synthesis of other crystals of similar scale will justify the system as flexible

This CDT will deliver impact aligned to the following agendas:

People
A2P will provide over 60 PhD graduates with the skill sets required to deliver innovative sustainable products and processes into the UK chemicals manufacturing industry. A2P will inspire and develop leaders who will:
- understand the needs of industrial end-users;
- embed sustainability across a range of sectors; and
- catalyse the transition to a more productive and resilient UK economy.

Economy
A2P will promote a step change towards a circular economy that embraces resilience and efficiency in terms of atoms and energy. The benefits of adopting more sustainable design principles and smarter production are clear. For example, the global production of active pharmaceutical ingredients (APIs) has been estimated at 65,000-100,000 tonnes per annum. The scale of associated waste is > 10 million tonnes per annum with a disposal cost of more than £15 billion. Consequently, even a modest efficiency increase by applying new, more sustainable chemical processes would deliver substantial economic savings and environmental wins. A2P will seek and deliver systematic gains across all sectors of the chemicals manufacturing industry. Our goals of providing cross-scale training in chemical sciences with economic and life- cycle awareness will drive uptake of sustainable best practice in UK industry, leading to improved economic competitiveness.

Knowledge
This CDT will deliver significant new knowledge in the development of more sustainable processes and products. It will integrate the philosophy of sustainability with catalysis, synthetic methodology, process engineering, and scale-up. Critical concepts such as energy/resource efficiency, life cycle analysis, recycling, and sustainability metrics will become seamlessly joined to what is considered a 'normal' approach to new molecular products. This knowledge and experience will be shared through publications, conferences and other engagement activities. A2P partners will provide efficient routes to market ensuring the efficient translation and transferal of new technologies is realised, ensuring impact is achieved.

Society
The chemistry-using industries manufacture a rich portfolio of products that are critical in maintaining a high quality of life in the UK. A2P will provide highly trained people and new knowledge to develop smarter, better products, whilst increasing the efficiency and sustainability of chemicals manufacture.
To amplify the impacts of our CDT, effective public engagement and technology transfer will become crucially important. As a general comment, 'sustainability' styled research is often regarded in a positive light by society, however, the science that underpins its effective implementation is often poorly appreciated. The University of Nottingham has developed an effective communication portfolio (with dedicated outreach staff) to tackle this issue. In addition to more traditional routes of scientific communication and dissemination, A2P will develop a portfolio of engagement and outreach activities including blogs, webpages, public outreach events, and contribution of material to our award-winning YouTube channel, www.periodicvideos.com.

A2P will build on our successful Sustainable Chemicals and Processes Industry Forum (SCIF), which will provide entry to networks with a wide range of chemical science end-users (spanning multinationals through to speciality SMEs), policy makers and regulators. We will share new scientific developments and best practice with leaders in these areas, to help realise the full impact of our CDT. Annual showcase events will provide a forum where knowledge may be disseminated to partners, we will broaden these events to include participants from thematically linked CDTs from across the UK, we will build on our track record of delivering hi-impact inter-CDT events with complementary centres hosted by the Universities of Bath and Bristol.