Creating novel biochemical engineering investigative tools and fundamentals speeding the discovery of bioprocesses for manufacturing at scale of new therapies and products of industrial biotechnology
Research in this area focuses on the creation of novel technologies to speed the creation of efficient, safe and sustainable bioprocesses. Uniquely we address solutions at scales from microlitre to small pilot scale.
- Bioprocess microfluidics. Here we work at microlitre scale to carry out studies in highly defined processing environments.
- Ultra Scale-Down (USD) technologies. Here we work at millilitre scale to provide both process understanding and scale down mimics.
- Microwell automation. Here we work at millilitre scale to provide scale-down information relating to process robustness.
- Manufacturing technologies. Here we use combinations of scale down investigations and flow analyses for high throughput investigations of single-use versus conventional manufacturing options with verification at pilot scale.
The EPSRC-funded Innovative Manufacturing Research Centre for Bioprocessing (2002-2012) hosted at UCL provided the basis for the creation of ultra scale-down technologies for recovery, purification and formulation operations. These resulted in the means of working with small (millilitre) amounts of precious materials available at early discovery stage and to understand how they would interact with the bioprocess environment which might exist at full manufacturing scale. For example, the impact of high hydrodynamic stress levels in the presence of hostile (e.g. air liquid) interfaces can be critical when dealing with materials ranging from therapeutic proteins, their engineered fragments or fusions to vaccines to human cells for therapy.
Figure 1: USD filtration – understanding how my material will perform.
Industry collaborative links in particular via the EPSRC Industrial Doctoral Training Centre and via Innovate UK have facilitated the verification of this work at scale with a wide range of challenging biomaterials. This has now led to the establishment of a HEFCE enterprise programme to help speed the knowledge transfer of these and next generation ultra scale-down technologies.
UCL Biochemical Engineering is now leading the way in high throughput bioprocessing with technologies complementary to ultra scale-down expertise via the introduction of lab on a chip, and microfluidic and microscale process platforms, the extension to fermentation and cell culture and their application to the synthesis and processing of industrial biotechnology products. Studies on novel technologies are informed by characterisation of fluid flow dynamics using particle image velocimetry (PIV) and advanced imaging techniques to define scaling laws and help elucidate the impact of complex flow regimes on process performance. The department is pursuing these activities via national and international collaborations, both academic and industrial.
Figure 2: USD capillary stress- cells for therapy need to survive processing
- High throughput bioprocess design
- Bioprocess microfluidics
- Miniature bioreactors
- Bioprocess automation
- Single-use technologies
Rios-Solis L, Morris P, Grant C, Odeleye AOO, Hailes HC, Ward JM, Dalby PA, Baganz F, Lye GJ. (2015) Modelling and optimisation of the one-pot multi-enzymatic synthesis of chiral alcohols based on microscale kinetic parameter determination. Chem. Engng. Sci., 122, 360-372. doi:10.1016/j.ces.2014.09.046
Betts JPJ, Warr S, Finka G, Uden M, Town M, Janda JM, Baganz F, Lye GJ. (2014) Impact of aeration strategies on fed-batch cell culture kinetics in a single-use 24-well miniature bioreactor. Biochem. Eng. J., 82, 105-116. doi:10.1016/j.bej.2013.11.010
Chatel A, Kumpalaume P, Hoare M. (2014) Ultra scale-down characterisation of the impact of conditioning methods for harvested cell broths on clarification by continuous centrifugation - recovery of domain antibodies from rec E. coli. Biotech Bioeng, 111, 913–924. doi:10.1002/bit.25164
Halim M, Rios-Solis L, Micheletti M, Ward JM, Lye GJ. (2014) Microscale methods to rapidly evaluate bioprocess options for increasing bioconversion yields: Application to the ω-transaminase synthesis of chiral amines. Bioproc. Biosys. Engng., 37(5), 931-941. doi:10.1007/s00449-013-1065-5
Lau EC, Kong SY, McNulty S, Entwisle C, Mcilgorm A, Dalton KA, Hoare M. (2013) An ultra scale-down characterization of low shear stress primary recovery stages to enhance selectivity of fusion protein recovery from its molecular variants. Biotech Bioeng, 110, 1973-1983. doi:10.1002/bit.24865
Lawrence J, O’Sullivan B, Lye GJ, Wohlgemuth R, Szita N. (2013) Microfluidic multi-input reactor for biocatalytic synthesis using transketolase. J. Molecular Catalysis B: Enzymatic, 95, 111-117. doi:10.1016/j.molcatb.2013.05.016
Li Q, Aucamp J, Tang A, Chatel A, Hoare M. (2012) Use of focused acoustics for cell disruption to provide ultra scale-down insights of microbial homogenization and its bioprocess impact-recovery of antibody fragments from rec E. coli. Biotech Bioeng, 109, 2059–2069. doi:10.1002/bit.24484
Acosta-Martinez JP, Papantoniou I, Lawrence K, Ward S, Hoare M. (2010) Ultra scale-down analysis of the bioprocessing of whole human cells as a basis for cancer vaccines. Biotech Bioeng, 107, 953-963. doi:10.1002/bit.22888
Reid CQ, Tait A, Baldascini H, Mohindra A, Racher A, Bilsborough S, Smales CM, Hoare M. (2010) Rapid whole monoclonal antibody analysis by mass spectrometry: an ultra scale-down study of the effect of harvesting by centrifugation on the post-translational modification profile. Biotech Bioeng, 107, 85-95. doi:10.1002/bit.22790
UCL Biochemical Engineering leaders in development of new high throughput process design strategies include:
Dr Frank Baganz (fermentation)
Dr Dan Bracewell (purification)
Prof Mike Hoare (ultra scale-down)
Prof Gary Lye (single use and bioreactors)
Dr Martina Micheletti (single use and flow dynamics)
Prof Nicholas Szita (microfluidics)
Dr Yuhong Zhou (automation and design)
Key collaborators include:
Prof Graham Ball (NTU), Prof Dan Caşcaval (TUI, Iaşi), Prof Anca-Irina Galaction (UMPI,Iaşi), Prof Krist V Gernaey (DTU), Prof Friedrich Götz (Tübingen), Prof Alfonso Jaramillo,(Genopole Paris), Rainer Krull (BraunschweigTUB), Prof Oscar Kuiper (Groningen), Dr Torsten Mayr /Bernd Nidetzky (Graz TUG), Jerome Morchain (LISBP, INSA- Toulouse), Prof Alessandro Paglianti (Bologna), Prof Sven Panke (ETH Zurich), Dr Gerardo Perozziello (Catanzaro), Markus Schmidt (IDC Vienna), Adama Sesay (Kajaani/Oulu),Dr Alice Temple (Leeds), Prof Ralf Wagner (Regensburg), Prof John Woodley (DTU), Polona Znidarsi Plazl (Ljubljana UL).
Dr Tony Allman (Infors), Tibor Anderlei (Kuhner), Marko Blom (Micronit BV), Dominique Bouwes (iX-factory), Dr Richard Davies (UCB), Dr Philip Engel (Evonik), Jorge Fernandez (NanoMyP),Claudia Gärtner (Microfludic Chipshop), Per Stobbe (CerCell), Steve Ward (Cell Therapy Catapult).