Scale up Bioreactors
Lec 4
SCALE-UP OF BIOPROCESSE
• All bioprocesses begin in the research laboratory and, if successful, finish in the
production plant.
• In transferring a laboratory scale process to the production scale, many diverse
problems are likely to be encountered, which have to be overcome if scale-up is
to be satisfactorily achieved.
• Preliminary process trials are normally conducted on a shake-flask scale, the
culture volume being 100-1000 mL.
• On the production scale, the culture volume will probably be in the range
of 25,000-10,00,000 L.
• An enormous increase in volume has therefore, to be accommodated in
most scaling-up exercises.
• It would not be practical or economical to attempt to transfer results from
the laboratory to the production plant in a single step.
• Step-up is usually accomplished in discrete stages, involving several
laboratory and pilot plant scales of operation.
• The problems can arise at any or all of the stages of scale-up.
Main Problem Areas
• Apart from some minor problems like antifoam toxicity, trace metal pick-up, etc., three major
problem areas in the scale-up are:
1.
Inoculum development
Generally, fermentation products are secondary metabolites which are generated in the resting
phase of the microbial growth.
• It is a common practice to employ large volumes of inoculum on the production scale (e.g., 10%)
in order to shorten the initial growth phase of the production stage fermentation and thus to
make better use of available plant capacity.
• In order to provide these large volumes of inoculum, it is necessary to conduct seed-stage
fermentations in the production plant. The additional stage frequently causes scale-up problems
due to culture degeneration or the altered metabolic stage of the organism at the time of
inoculation.
2. Medium sterilization
• For obvious economic reasons, crude technical grade medium constituents
are employed on the production scale.
• The impurities present in the chemicals may interfere directly or indirectly
during the medium sterilization.
• Commercial scale production using microbial fermentation process
requires large quantities of medium, scope of microbial contamination is
also very high.
• Sterilization of this medium takes a long time even up to 3-6 hours with a
severe heat treatment.
• This thermal process may degrade the essential nutrients and form toxic
compounds.
• These phenomena adversely affect the nutritive quality of the medium,
thereby resulting in lower yield of the product.
3. Aeration-agitation
• Shake-flask fermentation technique used in the laboratory scale is
unsuitable for commercial scale production because of the limitation of
oxygen transfer.
• Pilot and production scale fermentations are usually conducted in sparger
aerated, fully baffled, stirred cylindrical vessels, where many different
variables such as impeller speed, impeller geometry, air flow rate, air
pressure or the complex interactions of these have an effect on the oxygen
transfer.