Towards biofilm reactors for flow biocatalysis: investigating the productivity of biofilms for commodity chemical production in a microfluidic scale-d

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Title: Towards biofilm reactors for flow biocatalysis: investigating the productivity of biofilms for commodity chemical production in a microfluidic scale-down modelSupervisors and affiliationsProfessor Nicolas Szita, University College London Professor Gary Lye, University College LondonCollaborating academics at UCL Dept Biochemical Engineering Professor John Ward, Dr Marco Marques, Dr Duygu Dikicioglu,Collaborating academics outside UCLProf Nigel Scrutton, University of ManchesterContextThe field of continuous flow synthesis has grown significantly over the last two decades. Whilst the application of continuous flow focussed more on chemical synthesis initially, recently the use of whole cells and enzymes for biocatalytic synthesis has become popular. The use continuous flow for biocatalytic synthesis is termed 'Flow Biocatalysis'. Continuous flow allows the biocatalytic process to be performed in a heterogeneous catalysis regime. More importantly, flow biocatalysis reactors offer improved mass and heat transfer, automation (reducing process variations), in-line purification and pressurised operation. And the flow systems can be integrated with process analytical technology (PAT). Flow Biocatalysis therefore enables the establishment of new process windows for the synthesis of pharmaceuticals, value-added chemicals, and materials.Aims and ObjectivesIn this PhD project, we will evaluate and further explore the use of biofilms specifically for their application in flow biocatalysis (whole-cell biocatalysis) and flow biocatalysis reactors for commodity chemicals production.The first hypothesis to test is thus whether a microfluidic culture device can be employed for forming and maintaining biofilms in the device. Evaluating how well the biofilm and the bacterial culture can be retained in (or limited to) the culture chamber area will be of particular interest (given the continuous, perfusion mode of the device).The second hypothesis is that conditions can be found where the cells in a biofilm outperform non-biofilm growing cells. Related to that, as a sub-hypothesis, that biofilm-based systems outperform enzyme-based systems. Metrics for comparison include productivity of citramalate per cell mass (enzyme protein mass), yield of citramalate on substrate, and space time yield where possible (reactor configuration), for different dilution rates, i.e. different levels of hydrodynamic shear stresses.Research MethodologyConditions to investigate will include single biofilm growing bacteria vs co-culture, concentration of carbon source (potentially different types), cell growth substrate, hydrodynamic shear stress (in high shear environments, biofilms may be flatter or form long strands), and physico-chemical conditions, such as hydrodynamic shear stress and dissolved oxygen levels. By analysing the productivity per cell, we will determine optimal conditions for the biofilms.The knowledge gained from this research is expected to provide design criteria for flow biocatalysis reactors, such as the structural/scaffold support to maintain optimal metabolite producing conditions at different scales. Of interest could be biofilm-immobilisation structures, such as surface-immobilised biofilms, monoliths to scaffold biofilms, and porous/hydrogel-like beads which may foster particular spatial arrangements for the biofilm.Alignment to EPSRC's strategies and research areasThe project aligns with Future Manufacturing Technologies