Intelligent Continuous-flow Polymer Synthesis

This project will develop novel, artificially intelligent (AI) continuous-flow (CF) platforms for the manufacture of complex polymers. The aim is to open new design opportunities for sophisticated pharmaceuticals, while ensuring commercial manufacture is cost-effective, green and safe.
Polymers are long chain molecules which interact with each other in a manner which results in a diverse range of physical properties. Polymeric materials are often extremely strong, flexible and insulating. Due to their diversity, more polymers are manufactured than any other man-made material. Without them we would not be able maintain our current quality of life.
Often overlooked are 'speciality' or 'precision' polymers, which are present in many high-tech or performance products such as electronics, pesticides, lubricants, coatings and pharmaceuticals. Block copolymers, where two distinct polymer chains are tethered together, are of particular interest; especially when each block has considerably different properties. Although these are manufactured on a much smaller scale, they are often key contributors to a products functionality. Perhaps the most complex applications are within healthcare (e.g. drug delivery), where the drive toward 'personalised medicine' will benefit from polymers which are able to respond to local conditions (e.g. temperature or pH in a tumour). These can be used for patient specific, targeted and controlled delivery of drugs. These products will never become a reality unless precise, cost-effective and reproducible methods of manufacture are developed.
Continuous-flow is an alternative method of manufacturing chemicals to traditional stirred tanks. It involves continuously pumping the reaction medium through specially designed reactors meaning only a very small amount of material is under reaction conditions at any one time. The benefits of this technique are becoming more relevant in the drive for a sustainable manufacturing. It is often regarded as the greenest, safest and most cost-effective method of chemical manufacture. It is also a multi-scale technique, which is a considerable advantage since the demand for speciality polymers is likely to fluctuate significantly. In this context, larger volumes of product can be prepared by simply running the system for longer, removing any considerations that would be required with batch scale-up.
One of the most interesting aspects is the facile incorporation of online monitoring and feedback technology. This is essentially creating artificially intelligent (AI) reactors which will be able to immediately modify conditions to achieve the desired product without human intervention. This provides additional efficiency and potential cost savings.
During this project, a suitable continuous-flow reactor will be designed, constructed and evaluated for synthesis of a water based block copolymer. Following this, additional monitoring equipment will be added which will enable remote programming. Real-time monitoring of the conditions and the polymer produced will feed into a program capable of changing the conditions to achieve a product with a composition within defined limits. The system will subsequently be used to synthesise polymers which can respond to local temperature or pH by transitioning between soluble chains and particles. These particles will be capable of encapsulating an active ingredient, and releasing it during the transition to soluble chains which occurs on encountering specific conditions (e.g. inside a tumour).

Continuous-flow (CF) polymerisation technologies have the potential to revolutionise the polymer industry by providing a safe, cheaper, reproducible and scalable means of manufacturing speciality polymers. These benefits are already evident in small molecule synthesis, with reduction in the energy, solvents, water, waste and overall carbon footprint. The smaller footprint of reactors will mean less space is required within factories while improved reliability will minimise shutdowns for cleaning or repair. Better mixing and temperature control is achievable in advanced reactor technologies thus improving product quality. CF is also considerably safer, especially when autonomously controlled. Operators will encounter less hazardous material and explosion risks are mitigated since a relatively small volume of material is polymerising at any one time. Companies such as Synthomer, Ashland, BASF and GEO would benefit in this regard.
The polymers developed in this proposal have the potential to be included into the next generation of healthcare technologies. Drug formulations with efficient targeting and appropriate release profiles could lead to significantly reduced dosages of expensive drug. They are also potential components of more advanced therapeutic technologies such as in gene delivery, artificial prosthetics, stem cell therapy and tissue engineering. The UK government will benefit from considerably reduced costs for the NHS due to more effective treatments. Better product quality and reproducibility will also be of importance during the R&D stages of drug development, especially when manufacturing formulations for clinical trials. This will initially benefit pharmaceutical companies (e.g. AstraZeneca, GSK, Novartis, Merck, Roche, Sanofi, Ely Lilly). Patients will also benefit from more effective treatments and reduced timescales between R&D and commercialisation.
As the advanced polymers become more affordable, they will have additional applications in the agrochemical, personal care, coatings, energy and automotive industries. These can be in the form of novel formulations, functional gels, lubricants, dispersants and rheology modifiers. These will help provide food security, enhance our well-being and minimise our impact on the environment. Obvious beneficiaries will be companies such as Syngenta, Bayer Crop Science, Proctor and Gamble, Unilever, Reckitt Benckiser, DSM, AkzoNobel, DuPont and Infineum. New experimental apparatus or reactors will be developed which are dedicated to CF polymer synthesis, but the technology may be transferable to other processes. These will be of interest to reactor manufacturers and distributors such as Cambridge Reactor Design, Uniqsys, Syrris, Vapourtec, Corning and Swagelock. The incorporation of online analysis and automation will result in new software algorithms and software packages which would be of interest for alternative processes. Companies such as Magritek, Bruker, Oxford Instruments, Nanalysis, ThermoFisher, Agilent, Waters and National Instruments will benefit in this regard.
The proposed research will immediately expand the capability of the iPRD, which is well-known for process chemistry R&D. The University of Leeds will directly benefit in this regard. The iPRD is part funded by the Leeds Regional Development fund so the reputation of Leeds city council will improved.
In terms of personnel, the PDRA and PhD student will become experts in polymer synthesis, continuous-flow chemistry and gain experience in programming. They will also be trained in scientific and transferable skills. Undergraduate project students will also benefit from involvement in a research project which will equip them for careers in academia or industry. Outreach activities will initiate an interest in science among the younger generation and raise the perception of polymers and of plastics in society. This should encourage responsible use and disposal of plastics.