Fig. 9.4

150 Litre pilot –scalebioreactor

Genentech 12,000 L animal cell bioreactor

Lonza 20,000 liter bioreactor

Scaling up the production process

Lecture 9 Animal Cell BiotechnologyScaling 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

Lecture 9 Animal Cell BiotechnologyScaling 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

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

Axial flow impellers

www.np.edu.sg

The blades are pitched at an angle

Suspension directed towards the base of the tank

-Effective lifting solids from the base of the tank

-Low shear properties

-Used for mixing shear sensitive processes:

mammalian cells 100-150 rpm

Marine

Hydrofoil

Lecture 9 Animal Cell BiotechnologyScaling up the production process

Butler, M. 2004. Animal cell culture and technology 2nd ed. London and New York:Garland Science/BIOS Scientific Publishers. P159.