Understanding the impact of shear stresses on different cell lines in the Allegro STR system

The first part of the project will aim to quantify maximum and average Reynolds stresses in the Allegro system at different operating conditions. This can be achieved by (i) designing an accurate scale down device able to reproduce the geometry, environment and flow dynamics characteristics of the large scale reactor and/or (ii) adapting the Allegro reactor in order to be optically accessible by experimental flow dynamics techniques and thus directly measuring stresses in the system. A second step will involve the selection of three representative cell lines and the use of existing or new USD tools to better understand cell response to the range of stresses previously measured in the Allegro STR. Analytical information will be collected at different stages of the cell culture step (metabolic profiles, cell counting, particle size distribution, Scanning Electron Microscopy among others) to quantify the extent of cell damage. The combination of the experimental results obtained in the two stages will provide a thorough and complete insight of the interaction between the bioreactor geometry, the operating conditions and the resulting stresses, in addition to the challenges faced at large scale and potential bottlenecks.

The experimental work could be combined with a modelling approach to provide better understanding of the relationship between gas flow rate/gas distribution patterns, which are experimentally challenging to measure, and cell damage under different operating conditions. This part of the project will result in predictive correlations, able to inform future scale-down model design and support the validation of scaling correlations and identification of optimal operating conditions at the large scale.

The CDT has a proven track record of delivering impact from its research and training activities and this will continue in the new Centre. The main types of impact relate to: (i) provision of highly skilled EngD and sPhD graduates; (ii) generation of intellectual property (IP) in support of collaborating companies or for spin-out company creation; (iii) knowledge exchange to the wider bioprocess-using industries; (iv) benefits to patients in terms of new and more cost effective medicines, and (v) benefits to the wider society via involvement in public engagement activities and impacts on policy.

With regard to training, provision of future bioindustry leaders is the primary output of the CDT and some 96% of previous EngD graduates have progressed to relevant bioindustry careers. These highly skilled individuals help catalyse private sector innovation and biomanufacturing activity. This is of enormous importance to capitalise on emerging markets, such as Advanced Therapy Medicinal Products (ATMPs), and to create new jobs and a skilled labour force to underpin economic growth. The CDT will deliver new, flexible on-line training modules on complex biological products manufacture that will be made available to the wider bioprocessing community. It will also provide researchers with opportunities for international company placements and cross-cohort training between UCL and SSPC via a new annual Summer School and Conference.

In terms of IP generation, each industry-collaborative EngD project will have direct impact on the industry sponsor in terms of new technology generation and improvements to existing processes or procedures. Where substantial IP is generated in EngD or sPhD programmes, this has the potential to lead to spin-out company creation and job creation with wider economic benefit. CDT research has already led to creation of a number of successful spin-out companies and licensing agreements. Once arising IP is protected the existing UCL and NIBRT post-experience training programmes provide opportunities for wider industrial dissemination and impact of CDT research and training materials.

CDT projects will address production of new ATMPs or improvements to the manufacture of the next generation of complex biological products that will directly benefit healthcare providers and patients. Examples arising from previous EngD projects have included engineered enzymes for greener pharmaceutical synthesis, novel bioprocess operations to reduce biopharmaceutical manufacturing costs and the translation of early stem cell therapies into clinical trials. In each case the individual researchers have been important champions of knowledge exchange to their collaborating companies.

Finally, in terms of wider public engagement and society, the CDT has achieved substantial impact via involvement of staff and researchers in activities with schools (e.g. STEMnet), presentations at science fairs (Big Bang, Cheltenham), delivery of high profile public lectures (Wellcome Trust, Royal Institution) as well as TV and radio presentations. The next generation of CDT researchers will receive new training on the principles of Responsible Innovation (RI) that will be embedded in their research and help inform their public engagement activities and impact on policy.