Industrial Microbiology Dr. Butler 2011

3. 150 Litre pilot –scale
Fig. 9.4 bioreactor

4. Genentech 12,000 L animal cell bioreactor

5. Lonza 20,000 liter bioreactor

6. Scaling up the production process

7. Lecture 9 Animal Cell Biotechnology
Scaling up the production process:
The Stirred Tank Reactor
Advantages
• homogeneous cell suspension
• controlled cell environment
• easy access to cell samples for viability/morphology
check
• easy transfer of cells to the next scale up step
Disadvantages
• oxygen supply critical for cell growth
• cells may by exposed to hydrodynamic shear forces

8. Lecture 9 Animal Cell Biotechnology
Scaling up the production process
Agitation
• 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

9. Use of chemical agents to reduce cell damage, such as
0.1% Pluronic F68:
synthetic copolymer of ethylene and propylene
oxide, reduces cell: bubble interaction by preventing
attachment of cells to bubbles

11. Axial flow impellers
The blades are pitched at an angle
Suspension directed towards the base of the Marine
tank
Hydrofoil
-Effective lifting solids from the base of the
tank
-Low shear properties
-Used for mixing shear sensitive processes:
www.np.edu.sg
mammalian cells 100-150 rpm

12. Lecture 9 Animal Cell Biotechnology
Scaling up the production process
Butler, M. 2004. Animal cell culture and technology 2nd ed. London and New York:Garland Science/BIOS Scientific Publishers. P159.