BENGG004: Advanced Bioreactor Engineering
Aims
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.
Learning Outcomes
Following completion of the course, students will have an understanding of:
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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
Learning Hours
Lectures: 35h
Case studies/practicals: 30h
Assessment
Three-hour assessment (70%), Coursework (30%)
Syllabus
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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.
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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.