Sterilisable, biocompatible, immersible, spectroscopic planar imaging system

Current bioreactors use offline testing to analyse the quality and status of their samples. This is a costly and wasteful process, and limits the frequency at which the bioreactor contents can be tested. It is proposed that a system could be developed using a sterilisable monolithic image transfer system to allow continuous measurement of the reactor contents, without damaging or removing cells. To do this, a dual system would be used; it would be composed of a high quality imaging system capable of spatial resolution to 10 micro m, coupled with a Raman system capable of measuring the concentration of key nutrients within the medium. The imaging system will be used to perform cell counting, in order to calculate the cell concentration within the medium. One of the key concerns for such a technique is the damage that might be caused by injecting light into the cells. Part of this body of research will therefore revolve around measuring and analysing the causes of phototoxicity and photomutagenicity in human stem cells. This will feed into the development of the prototype machine, affecting the illumination intensity and wavelength.The aim of the project would be to test the viability of a dual imaging/Raman system for use in the processing of human stem cells, to publish data regarding the efficacy of dual imaging/Raman systems, and to feed into UCL's existing bioengineering facilities. The project would also investigate the problems associated with using optical measurement systems on sensitive biological matter, such as phototoxicity and photomutagenicity, and what precautions can be taken to negate or mitigate them.The benefit expected of the proposed system would be the ability to measure nutrient concentration over scales of less than a minute, whilst simultaneously measuring the cell concentration. Due to the nature of the monolithic image transfer plate, the Raman system could potentially be extended to allow for Raman imaging that could provide sub-second images of nutrient movement around cells, opening up the potential for research into the uptake rate of various nutrients during cellular processes.In addition to the benefits brought by the system, researching phototoxicity and its effects should open up the possibility of other optical methods for use in bioreactors. This might not be limited to sensing technologies, but also intentional cell mutation using light, or the manipulation of cells using light.The project would take the form of designing and building a prototype system, before verifying and demonstrating its efficacy experimentally. Expert opinions from bioengineers within the department will be sought to find potential improvements that would make the device more useful in the development of industrial and hospital medicine.This technology would align with several EPSRC Healthcare challenges. In particular, it addresses Developing Future Therapies, as it would greatly improve the processes used in developing future therapies, by allowing online measurement of the reactor. Cell therapies are minimally invasive, and could remove the need for damaging surgeries to remove, for example, cancerous tumours, Which would align with the Frontiers of Physical Intervention challenge. It develops the tools vital to the quantitative analysis of cellular manufacturing techniques, addressing the Manufacturing priority New Industrial Systems.

The IDC 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 graduates; (ii) generation of intellectual property (IP) in support of collaborating companies or for new venture 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 wider society via involvement in public engagement activities and encouraging future generations of researchers.

With regard to training, the provision of future bioindustry leaders is the primary mission of the IDC and some 97% of previous EngD graduates have progressed to relevant bioindustry careers. These highly skilled individuals help catalyse the development and expansion of private sector innovation and biomanufacturing activity. This is of enormous importance to capitalise on emerging markets and to create new jobs and a skilled labour force to underpin the UK economy.

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 this has the potential to lead to spin-out company creation and job creation with wider UK economic benefit. IDC research has already led to creation of two UCL spin-out companies focussed on the emerging field of Synthetic Biology (Synthace) and novel nanofibre adsorbents for improved bioseparations (Puridify). Once arising IP is protected the IDC also provides a route for wider dissemination of project outputs and knowledge exchange available to all UK bioprocess-using companies. This occurs via UCL MBI Training Programme modules which have been attended by more than 1000 individuals from over 250 companies to date.

The majority of IDC projects address production of new medicines or process improvements for pharmaceutical or biopharmaceutical manufacture which directly benefit healthcare providers and patients. Examples arising from previous EngD projects have included: engineered enzymes used in the synthesis of a novel pharmaceutical; early stage bioprocess development for a new meningitis vaccine; redevelopment of the bioprocess for manufacture of the UK anthrax vaccine; and establishment of a cGMP process for manufacture of a tissue-engineered trachea (this was subsequently transplanted into a child with airway disease and the EngD researcher was featured preparing the trachea in the BBC's Great Ormond Street series). Each of these examples demonstrates IDC impact on the development of cost-effective new medicines and therapies. These will benefit society and provide new tools for the NHS to meet the changing requirements for 21st Century healthcare provision.

Finally, in terms of wider public engagement and society, the IDC has achieved substantial impact via involvement of staff and researchers in activities with schools (STEMnet, HeadStart courses), 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 IDC researchers will be increasingly involved in such outreach activities to explain how the potential economic and environmental benefits of Synthetic Biology can be delivered safely and responsibly.