Selection, Scale-up,

Operation and Control of

Bioreactors

ChE 3BK3
October 22, 2004
Chapter 10, Shuler & Kargi
Midterm
z Worth 25% of the final mark
z Held in class (MDCL 1010), Friday, October 29th,
9:30-10:20am
z Covers Chapters 1,2,3,6,7,9 (lectures 1-16)
z Open textbook, open notes
z Format: 3 questions, total of 40 marks
• Budget 1 minute per mark (so you should finish a 15
mark question in 15 minutes)
• Questions are problems similar to those you have seen
on the assignments
• Know the algorithm used to solve problems on each of
the topics we have covered to date
Outline
z Scale up
z Sample calculations
Scale Up
z Recall that fermenters growing microbial
cultures typically have a height-to-diameter
ratio of 2-3:1; 1:1 for animal cell culture
• However, if the H:D ratio remains constant, then the
surface-to-volume ratio decrease dramatically during
scale-up
• This decreases the relative contribution of surface
aeration vs sparging to oxygen supply
• For traditional bacterial fermentations, surface
aeration is unimportant, but for shear-sensitive
cultures, it can be critical because of restrictions on
sparging and stirring
Scale Up
z A more important consideration in bacterial
and fungal fermentations is wall growth
• If cells adhere to surfaces, it can be difficult to predict
performance in a large fermenter from data at the
small scale
z Even more critical is the fact that the physical
conditions in a large fermenter can never
exactly duplicate those in a smaller fermenter
if geometric similarity is maintained
• Depending on the sensitivity of a given organism
to changes in its environment, this can result in
dramatic differences in physiology, metabolism
and performance on scale-up
Scale Up
z Scale up rules can be used to establish which
parameters will be varied and how
z Rules:
• Constant power input (P0/V)
• Implies constant oxygen transfer rate (OTR)
• Constant impeller rotation number (N)
• Gives constant mixing times
• Constant speeds at the impeller tip (N·Di)
• Gives constant shear
• Constant Reynold’s number (Re)
• Gives geometrically similar flow patterns
Interdependence of Scale-Up
Parameters
Scale Up
z In practice, scale up is highly empirical,
meaning that the operating parameters for the
larger scale are often determined
experimentally (i.e. trial and error)
z Common to design for a constant kLa value, or
constant substrate (e.g. DO) or product level
on scale-up
• For example, if DO is a constant, then the setpoint
value for DO is maintained at the larger scale, and
other parameters (agitation speed, aeration rate, gas
mixture) are varied to ensure the setpoint is achieved
Scale Up Problems
z Predictable
• Mixing times
• Oxygen transfer
• Heat transfer
• Power input
• Aeration rates
z Difficult to predict
• Product quality (e.g. protein degradation)
• Foaming
• By-product formation
Economic Considerations on
Scale Up
z Relative cost of changes at various stages of
scale up:
• Pre-design phase 1
• Design phase 10
• Construction phase 100
• Plant in operation 1000
z Reactor types (CSTRs, bubble columns, loop
bioreactors)
z Changes in medium composition (serum-free)
Practical Operating Boundaries for
Aerated, Agitated Fermenters
Example 10.2
Example 10.2 - Solution
Example 10.3
Example 10.3 - Solution
Example 10.3 - Solution