Advanced Bioreactor Engineering
Professor Gary Lye
Three-hour assessment (70%)
This course provides students with a detailed understanding of bioreactor design, scale-up and operation. It considers both whole cell (i.e. fermentation) and enzymatic (i.e. biotransformation) conversion processes for the synthesis of complex materials such as therapeutic proteins, antibiotics, gene therapy vectors and chiral pharmaceuticals.
Particular themes of the course include the interaction of biological catalysts and pharmaceuticals with the engineering environment within a bioreactor, the theoretical basis of process scale-up and scale-down, and the impact of rDNA techniques on bioreactor design and operation. Particular attention is paid to the instrumentation and control of bioreactors and issues underlying biosafety with respect to contained operation.
Following completion of the course, students will have an understanding of:
- how to fully specify bioreactor design characteristics and monitoring and control systems
- how bioreactor operation and scale-up impacts on cell growth and productivity
- how the kinetics of both free and immobilised biocatalysts impact on bioreactor selection and operation
- how to relate this fundamental knowledge on bioreactor engineering to industrial practice
- the impact of rDNA techniques on biocatalyst kinetics and bioprocess design
Case studies/practicals: 30h
- Stoichiometry of biocatalyic processes: mass balancing, electron balancing and degrees of reduction
- Modes of bioreactor operation: growth kinetics, batch, fed-batch and continuous operation. Productivity optimisation and cost minimisation.
- Bioreactor design: size estimation, single or multiple vessels, impeller and sparger systems. Design for containment and asceptic operation.
- Bioreactor monitoring and control: instrumentation, on-line and off-line analyses, control algorithms.
- Bioreactor sterilisation: cell death kinetics, batch and continuous systems, filter sterilisation of gasses and liquids, safe and contained operation.
- Oxygen transfer: mass transfer theories and correlations, design for oxygen transfer, bubble size, gas hold-up.
- Mixing and power consumption: power number and impeller design, mixing time and reactor heterogeneity, effect of aeration and broth rheology.
- Effects of shear: influence of shear on hydrodynamics and microorganisms and Kolmogoroff concept of turbulence.
- Issues in process scale-up: effects of heterogeneity and bases for scale-up.
- Fermentation process scale down: benefits of process scale down, regime analysis and strategies for scale down experimentation including process automation.
- Fundamentals of biological catalysis: biocatalyst production, biocatalyst form and implications of rDNA technology.
- Biocatalyst kinetics and properties: enzyme immobilisation, kinetics of free and immobilised enzymes, biocatalyst characterisation.
- Biocatalytic reactors: reactor design equations, reactor selection and operation.
- Improving bioreactor productivity: implications of two-liquid-phase biocatalysis and in-situ product removal.
- Industrial lectures: impact of microbial physiology on bioreactor performance, Present and future fermentation trends, Scale-up and scale-down of industrial fermentation processes, Rapid fermentation process development, Industrial applications of biocatalysis, Genetic techniques for biocatalyst improvement.