EPSRC Innovative Manufacturing Research Centre (IMRC) in Bioprocessing
The multi-disciplinary Innovative Manufacturing Research Centre (IMRC) in Bioprocessing draws upon academic expertise from a wide range of UCL departments as well as from recognised experts in other institutions throughout the UK. The IMRC has a single focus:
- To change fundamentally the ways in which bioprocesses are developed for the manufacture of complex and highly specific next-generation biopharmaceuticals.
The research activities of the IMRC are designed to meet this goal as set out below. Collaborative doctoral and post-doctoral projects are currently underway in each of these and funded by a combination of BBSRC, EPSRC and Technology Strategy Board awards.
- Novel approaches to the creation of microscale mimics of key unit operations.
- Engineering studies to construct sequences of bioprocess operations on automated platforms for rapid bioprocess creation and optimisation.
- Development of intelligent experimental design algorithms to make best use of microscale approaches.
- Creation of techniques to maximise knowledge acquisition from sparse datasets.
- The use of host cell engineering to remove process bottlenecks.
- Identification and deployment of smart downstream process solutions designed to achieve significant improvements to process yield and efficiency.
IMRC studies consider the whole bioprocess division. The improvements in overall process peformance that may be realised by all engineering for example, can be mimiced using multi litre quantities of materials and then verified in the unique pilot-plant facilities at UCL.
The IMRC programme products employs a series of industrially relevant expression systems and macromolecular products to explore the challenges and to illustrate its research successes. These include expression of antibody fragments in E.coli, whole antibodies in mammalian cell lines and virus-like particles from S. cerevisiae.
A multi-disciplinary group of UCL academics with an extensive history of close collaboration work to deliver the IMRC vision. These include Professor Mike Hoare (micro-scale bioprocessing), Professor Nigel Titchener-Hooker (whole bioprocessing), Professor John Ward (cell engineering), Dr Tony Hunter (Computer Science, knowledge acquisition), Dr Dan Bracewell (smart downstream processing), Dr Yuhong Zhou (intelligent design methods), Dr Eli Keshavarz-Moore (fermentation) and Dr Frank Baganz (metabolic modelling and engineering).
A consortium of 12 companies supports the programme financially and through the promotion of industrial strains and materials. Additionally they form an industrial Steering Group to assist in the direction of the programme. A senior Management Committee provides strategic direction to the IMRC and in particular helps with outreach via the KTNs and other IMRCs. Current consortium members include: BioPharm Services (UK), Eli Lilly (UK & USA), GE Healthcare (UK & EU), GSK (UK), Health Protection Agency (UK), Lonza Biologics (UK, EU & USA), Medimmune (UK), Merck (USA), Novo Nordisk (EU), Protherics (UK), Pfizer (UK & USA) and UCB (UK).
The capacity to determine critical engineering parameters early in evolution of a bioprocess design lies at the heart of the IMRC philosophy. Increasingly we are employing the use of highly automated and miniaturised systems to investigate key aspects of bioprocess behaviour.
The IMRC sponsors regular IMRC Bioprocess Briefing at UCL which are open to all. Outreach to the community is further stimulated by Special Interest Groups (SIGs), for example on the use of microwell technologies in bioprocess discovery and optimisation. The IMRC hosts an annual meeting each September to showcase its success and the extensive collaborations both academic and industrial that it supports.
Understanding the impact of press changes is critical if advances are to be made across the unit operations within a bioprocess. Pioneering confocal microscopy studies of the impact that foulants have on the uptake of product molecules during adsorption are typical of the fundamental studies underway within the IMRC.
To find out more, download a leaflet.
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Selected IMRC publications
Boychyn, M., Yim, S.S.S., Bulmer, M., More, J., Bracewell, D.G., Hoare, M. (2004). Performance prediction of industrial centrifuges using scale-down models. Bioprocess and Biosystems Engineering, 26, 385-391.
Chan, G., Booth, A.J., Mannweiler, K., Hoare, M. (2006). Ultra scale-down studies of the effect of flow and impact conditions during E.coli cell processing. Biotechnology and Bioengineering, 95(4), 671-683. DOI: 10.1002/bit.21049
Hutchinson, N., Bingham, N., Murrell, N., Farid, S., Hoare, M. (2006). Shear stress analysis of mammalian cell suspensions for prediction of industrial centrifugation and its verification. Biotechnology and Bioengineering, 95(3), 483-491. DOI: 10.1002/bit.21029
Islam, R.S., Tisi, D., Levy, M.S., Lye, G.J. (2007). Framework for the Rapid Optimization of Soluble Protein Expression in Escherichia coli Combining Microscale Experiments and Statistical Experimental Design. Biotechnology Progress, 23(4), 785-793. DOI: 10.1021/bp070059a
Jackson, N.B., Liddell, J.M., Lye, G.J. (2006). An automated microscale technique for the quantitive and parallel analysis of microfiltration operations. Journal of Membrane Science, 276, 31-34. DOI: 10.1016/j.memsci.2005.09.028
Kong, S., Titchener-Hooker, N.J., Levy, M.S. (2006). Plasmid DNA processing for gene therapy and vaccination: studies on the membrane sterilisation filtration step. Journal of Membrane Science, 280, 824-831. DOI: 10.1016/j.memsci.2006.03.003
Pampel, L., Boushaba, R., Udell, M., Turner, M., Titchener-Hooker, N.J. (2007). The influence of major components on the direct chromatographic recovery of a protein from transgenic milk. Journal of Chromatography A, 1142(2), 137-147. DOI: 10.1016/j.chroma.2006.12.043
Wenger, M.D., DePhillips, P., Price, C.E., Bracewell, D.G. (2007). An automated microscale chromatographic purification of virus-like particles as a strategy for process development. Biotechnology and Applied Biochemistry, 47, 131-139.
Willoughby, N., Martin, P., Titchener-Hooker, N. J. (2004). Extreme scale-down of expanded bed adsorption: purification of an antibody fragment directly from recombinant E. coli culture. Biotechnology and Bioengineering, 87(15), 641-647. DOI: 10.1002/bit.20173
Whole Bioprocess Modelling
Bracewell, D.G., Brown, R.A., Hoare, M. (2004). Addressing a whole bioprocess in real-time using an optical biosensor-formation, recovery and purification of antibody fragments from a recombinant E. coli host. Bioprocess and Biosystems Engineering, 26, 271-282.
Siu, S.C., Boushaba, R., Liau, J., Hjorth, R., Titchener-Hooker, N.J. (2007). Confocal imaging of chromatographic fouling under flow conditions. Journal of Chemical Technology and Biotechnology, 82(10), 871-881. DOI: 10.1002/jctb.1728
Chhatre, S., Jones, C., Francis, R., Oâ€™Donovan, K., Titchener-Hooker, N.J., Newcombe, A.R., Keshavarz-Moore, E. (2006). The integrated simulation and assessment of the impacts of process change in biotherapeutic antibody production. Biotechnology Progress, 22, 1612-1620. DOI: 10.1021/bp0602000
Hoare, M.,Levy, M.S., Bracewell, D.G., Doig, S.D., Kong, S., Titchener-Hooker, N.J., Ward, J.M., Dunnill, P. (2005). Bioprocess engineering issues that would be faced in producing a DNA vaccine at up to 100m3 fermentation scale for an influenza pandemic. Biotechnology Progress, 21(6), 1577-1592. DOI: 10.1021/bp050190n
Joseph, J., Sinclair, A., Titchener-Hooker, N.J., Zhou, Y. (2006). A framework for assessing the solutions in chromatographic process design and operation for largescale manufacture. Journal of Chemical Technological Biotechnology, 81, 1009-1020.
King, J. M. P., Titchener-Hooker, N. J. and Zhou, Y. (2007) Ranking bioprocess variables using global sensitivity analysis: A case study in centrifugation. Bioprocess and Biosystems Engineering, 30, 123-134.
Salisbury, R.; Bracewell, D.; Titchener-Hooker, N.J. (2006). A methodology for the graphical determination of operating conditions of chromatographic sequences incorporating the tradeoffs between purity and yield. Journal of Chemical Technology and Biotechnology, 81(11), 1803-1813.
Salte, H., King, J., Baganz, F., Hoare, M., Titchener- Hooker, N. (2006). A methodology for centrifuge selection for the separation of high solids density cell broths by visualisation of performance using Windows of Operation. Biotechnology and Bioengineering, 95(6), 1218-1227. DOI: 10.1002/bit.21102
Biddlecombe, J.G., Craig, A.V., Zhang, H., Uddin, S., Mulot, S., Fish, B.C., Bracewell, D. G. (2007). Determining Antibody Stability: Creation of Solid-Liquid Interfacial Effects within a High Shear Environment. Biotechnology Progress, 23, 1218-1222. DOI: 10.1021/bp0701261
Mannall, G., Titchener-Hooker, N.J., Chase, H., Dalby, P. (2006). A critical assessment of the impact of mixing on dilution refolding. Biotechnology and Bioengineering, 93, 955-963. DOI: 10.1002/bit.20796
Meacle, F.J., Lander, R., Ayazi Shamlou, P., Titchener- Hooker, N.J. (2004). Impact of engineering flow conditions on plasmid DNA yield and purity in chemical cell lysis of operations. Biotechnology and Bioengineering, 87(3), 293-302. DOI: 10.1002/bit.20114
Meacle, F.J., Zhang, H., Papantoniou, I., Ward, J.M., Titchener-Hooker, N.J., Hoare, M. (2007) Degradation of supercoiled plasmid DNA within a capillary device. Biotechnology and Bioengineering, 97(5), 1148-1157. DOI: 10.1002/bit.21275
Nealon, A.J., Oâ€™Kennedy, R.D., Titchener-Hooker, N.J. and Lye, G.J. (2006). Quantification and prediction of jet macro-mixing times in static microwell plates. Chemical Engineering Science, 61, 4860-4870.
Siu, S.C., Baldascini, H., Hearle, D.C., Hoare, M., Titchener-Hooker, N.J. (2006). Effect of fouling on the capacity and breakthrough characteristics of a packed bed ion exchange chromatography column. Bioprocess and Biosystems Engineering, 28, 405-414.
Tran, R., Joseph, J.R., Bracewell, D., Zhou, Y., Titchener- Hooker, N.J. (2007). A framework for the prediction of scale-up when using compressible chromatographic packings. Biotechnology Progress, 23(2), 413-422. DOI: 10.1021/bp060303i
Zhang, H., Kong, S., Booth, A., Boushaba, R., Levy, M.S., Hoare, M. (2007) Prediction of shear damage of plasmid DNA in pump and centrifuge operations using an ultra scale-down device. Biotechnology Progress, 23(4), 858-865. DOI: 10.1021/bp070066z