Bioprocess Recovery and Purification
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||Professor Ajoy Velayudhan|
Unseen written examination 3h (50%)
Presentation + log book (13%)
To provide training for second year biochemical engineers, via lectures, case studies and pilot plant study, in the engineering principles underlying the operations and processes for the recovery and purification of biological materials. The course focuses on how operations need to be integrated to create a whole sequence where issues of ease of operation, safety and environmental impact are considered at the selection stage.
Expert Lectures: 30h
Industry Expert Seminars: 10h
Pilot-plant study and observed student presentations: 60h
Report writing: 30h
- Three downstream processing practical reports (15% of overall mark)
- Two ultra scale-down practical reports (12.5% of overall mark)
- Downstream processing study (5% of overall mark)
- Monitoring and control study (15% of overall mark)
Stage 1 Taught course elements and case studies
- The recovery and purification of biological products from complex sources such as fermentation or cell culture represents the major challenge for the provision of safe and effective materials, for therapeutic use and for industrial applications.
- The course is designed to progress through the logic of a bioprocess sequence from basic cell removal through to high resolution purification and formulation.
- Particle recovery and purification processes are examined as the early stages in the separation of biological materials. Operations include centrifugation, filtration, membrane separation, precipitation and crystallisation. Complementary extraction operations include liquid/liquid reaction and cell disruption
- High resolution purification and finishing operations take the material to final form for use - operations studied include chromatography.
- The use of simulation to predict the performance of unit operations and of process sequences will be introduced together with graphical tools for visualising trade-offs.
- The course is concluded with a summary of how complete recovery and purification sequences may be best put together. This provides the ideal precursor to pilot plant studies and third/fourth year design projects
- Case studies in the design of selected operations will form the basis of team exercises to help with the understanding and application of the lecture notes.
Stage 2 Practical studies
Practical studies of 3-4 hours duration each allow detailed exploration of a range of purification stages including:
- Membrane separations
Students develop critical flux and transmission data for a range of membrane types (MF& UF) and seek to relate these performance metrics to established theory. By the use of different membrane geometries students also learn about the impact of shear in cross flow operation and discuss the influence of cartridge lengths and diameter on long-term membrane performance.
- Centrifugation: (2 practicals)
(a) Ultra scale-down predication of the industrial-scale centrifugal recovery of shear - sensitive biological materials
(b) Pilot scale verification of ultra scale-down predictions using continuous flow solid bowl and disc stack centrifuges.
The disruption of the cell wall to release intracellular products is a key stage in many processes – Students become familiar with bend melting and high pressure homogenisation techniques. Protein release data is modelled by classical first order kinetics. The practical augments theoretical lecture material and also considers aspects of safe operation and containment of high pressure (1000 gar) units.
This practical introduces the principles of packed bed column packing and testing of axial dispersion.
Each unit operation practical is conducted in purpose-designed facilities following defined SOPs. Skilled and trained demonstrators provide hands-on assistance alongside professional full time technical staff in the delivery of these elements. Students are required to conduct detailed investigations of the operating characteristics and performance of the major operations that comprise modern processes. Integral to these are a full understanding of underlying mass and heat transfer processes that govern operations behaviour.
Practicals are assessed via formal written reports structured in such a way as to draw out any appreciation of the underlying mechanisms of operation as well as a detailed knowledge of safety aspects.
Stage 3 Whole bioprocess pilot plant study
The whole bioprocess sequence from fermentation through recovery and purification is examined in a pilot plant exercise embraces many aspects of novel research interest within the department. This exercise builds planning and presentation skills and also provides candidates with direct hands-on experience in the safe operation and control of complex unit operations.
Students, grouped in teams of 5 or 6, will engage with the production of a wide range of products ranging from enzymes, small molecules, antibodies and virus-like particles. Some groups will also explore scale-up/down techniques.