Lecture 91b scaling up

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Industrial Microbiology Dr. Butler 2011

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Lecture 91b scaling up

  1. 1. 150 Litre pilot –scaleFig. 9.4 bioreactor
  2. 2. Genentech 12,000 L animal cell bioreactor
  3. 3. Lonza 20,000 liter bioreactor
  4. 4. Scaling up the production process
  5. 5. Lecture 9 Animal Cell Biotechnology Scaling up the production process: The Stirred Tank ReactorAdvantages• homogeneous cell suspension• controlled cell environment• easy access to cell samples for viability/morphology check• easy transfer of cells to the next scale up stepDisadvantages• oxygen supply critical for cell growth• cells may by exposed to hydrodynamic shear forces
  6. 6. Lecture 9 Animal Cell Biotechnology Scaling up the production processAgitation• stirring at 100-150 rpm for cells in suspension, 40 rpm for micro-carriers• must be careful not to damage animal cells when stirring (shear force)• small size bioreactors (up to 1 L) – magnetic stir bar• larger bioreactors – motor driven impellors• to ensure adequate mixing at low stirring rates, animal cell culture reactors have round bottoms → bacterial – flat bottomed, higher stirring rates
  7. 7. Use of chemical agents to reduce cell damage, such as 0.1% Pluronic F68:synthetic copolymer of ethylene and propyleneoxide, reduces cell: bubble interaction by preventingattachment of cells to bubbles
  8. 8. Axial flow impellersThe blades are pitched at an angleSuspension directed towards the base of the Marinetank Hydrofoil-Effective lifting solids from the base of thetank-Low shear properties-Used for mixing shear sensitive processes: www.np.edu.sg mammalian cells 100-150 rpm
  9. 9. Lecture 9 Animal Cell Biotechnology Scaling up the production processButler, M. 2004. Animal cell culture and technology 2nd ed. London and New York:Garland Science/BIOS Scientific Publishers. P159.

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