1. Design of a Fermenter Abira Khan

2. Basic Functions of A Fermenter  To provide a controlled environment for the growth of microorganisms or animal cells, to obtain a desired product  A research team led by Chaim Weizmann in Great Britain during the First World War (1914-1918) developed a process for the production of acetone by a deep liquid fermentation using Clostridium acetobutylicum which led to the eventual use of the first truly large-scale aseptic fermentation vessels (Hastings, 1978)

3. Criteria for Fermenter Design  The vessel should be capable of being operated aseptically for a number of days and should be reliable in long- term operation and meet the requirements of containment regulations.  Adequate aeration and agitation should be provided to meet the metabolic requirements of the micro-organism. However, the mixing should not cause damage to the organism.  Power consumption should be as low as possible.  A system of temperature control should be provided.  A system of pH control should be provided.  Sampling facilities should be provided.  Evaporation losses from the fermenter should not be excessive.  The vessel should be designed to require the minimal use of labour in operation, harvesting, cleaning and maintenance.  Ideally the vessel should be suitable for a range of processes, but this may be restricted because of containment regulations.  The vessel should be constructed to ensure smooth internal surfaces, using welds instead of flange joints whenever possible.  The vessel should be of similar geometry to both smaller and larger vessels in the pilot plant or plant to facilitate scale-up.  The cheapest materials which enable satisfactory results to be achieved should be used.  There should be adequate service provisions for individual plant

5. Aseptic Operation and Containment  Different assessment procedures are used depending on whether or not the organism contains foreign DNA (genetically engineered)  Once the hazards are assessed, an organism can be classified into a hazard group for which there is an appropriate level of containment  Non-genetically engineered organisms may be placed into a hazard group (1 to 4) using criteria to assess. risk such as those given by Collins (1992): 1. The known pathogenicity of the micro-organism. 2. The virulence or level of pathogenicity of the micro-organism are the diseases it causes mild or serious? 3. The number of organisms required to initiate an infection. 4. The routes of infection. 5. The known incidence of infection in the community and the existence locally of vectors and potential reserves. 6. The amounts or volumes of organisms used in the fermentation process. 7. The techniques or processes used. 8. Ease of prophylaxis and treatment

7. Fermenter Design

8. Fermenter Body  Glass/Stainless steel  Two basic types: 1. A glass vessel with a round or flat bottom and a top flanged carrying plate 2. A glass cylinder with stainless-steel top and bottom plates  The corrosion resistance of stainless steel is thought to depend on the existence of a thin hydrous oxide film on the surface of the metal  The inclusion of nickel in high percent chromium steels enhances their resistance and improves their engineering properties  The presence of molybdenum improves the resistance of stainless steels to solutions of halogen salts and pitting by chloride ions in brine or sea water  Corrosion resistance can also be improved by tungsten, silicone and other elements

9. Temperature Control  Microbial activity, Stirring  Heating/Cooling Jackets

10. Aeration and Agitation  Primary purpose of aeration is to provide microorganisms in submerged culture with sufficient oxygen for metabolic requirements, while agitation should ensure that a uniform suspension of microbial cells is achieved in a homogeneous nutrient medium.  The of aeration-agitation system used in a particular fermenter depends on the characteristics of the fermentation process under consideration  The structural components of the fermenter involved in aeration and agitation are: 1. The agitator (impeller) 2. Stirrer glands and bearings 3. Baffles 4. The aeration system (sparger)

11. Achievement and Maintenance of Aseptic Conditions  Sterilization of the fermenter.  Sterilization of the air supply and the exhaust gas.  Aeration and agitation.  The addition of inoculum, nutrients and other supplements.  Sampling.  Foam control.  Monitoring and control of various parameters.

12. Other Fermentation Vessels  Waldhof-type fermenter  Tower fermenter  Air-lift fermenters-Inner/outer loop  Acetators and cavitators  Cylindro-conical vessels  Bubble column fermenter  Deep jet fermenter  Cyclone column  Packed tower  Rotating-disc fermenters

13. Animal Cell Culture  2 modes of growth: 1. Anchorage dependent cells. These cells require a solid support for their replication. They produce cellular protrusions (pseudopodia) which allow them to adhere to positively charged surfaces and often grow as monolayers. 2. Anchorage independent cells. These cells do not require a support and can grow as a suspension in submerged culture. Established and transformed cell lines are normally in this category

14. Animal Cell Culture  Stirred fermenters  Air-lift fermenters  Encapsulation  Hollow fibre chambers  Packed glass bead reactors  Perfusion/spin cultures

15. Valves  Valves attached to fermenters and ancillary equipment are used for controlling the flow of liquids and gases in a variety of ways.  The valves may be: 1. Simple ON/OFF valves which are either fully open or fully closed. 2. Valves which provide coarse control of flow rates. 3. Valves which may be adjusted very precisely so that flow rates may be accurately controlled. 4. Safety valves which are constructed in such a way that liquids or gases will flow in only one direction.

16. Valves  Check valves  Pressure-control valves- pressure-reduction valves, pressure-retaining valves  Safety valves  Steam traps

17. Reference  Principles of Fermentation Technology- Stanbury- 2nd edition, Chapter 7