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Dr.

Saleha Shamsudin
Generally, fermenters maintain a height-to-
diameter ratio of 2-to-1 or 3-to-1. If the height-to-
diameter ratio remains constant, then the surface-
to-volume ratio decreases dramatically during
scale-up.

This change decreases the relative contribution of


surface aeration to oxygen supply and dissolved-
carbon-dioxide removal in comparison to the
contribution from sparging.
If cells have altered metabolism due to mass
transfer limitations, then data obtained in a small
fermenter may be unreliable in predictiong
culture response in a larger fermenter.

Perhaps even more importantly, it can be shown


that the physical conditions in a large fermenter
can never exactly duplicate those in a smaller
fermenter if geometric similirity is maintained.
Four cases are treated in Table 10.2:

1.Scale-up based on Constant power input


(Po/V)
2.Scale-up based on Constant liquid
circulation rate inside the vessel, (Q/V)
3.Scale-up based on Constant shear at
impeller tip (NDi)
4.Scale-up based on Constant Reynolds
number (NDi2р/μ)
Note that,
3 3 5 3 p Q
PN D VDi QNDi
i N Di
3 2
N
V V
Fixing N and Di fixes all the quantities in Table 10.2.
Since these quantities have different dependencies
on N and Di, a change of scale must result in the
changes in the physical environment that the cells
experience. When these changes alter the
distribution of chemical species in the reactor, or
they destroy or injure cells, the metabolic response
of the culture will differ from one scale to another.
In some cases cells respond to modest changes in mechanical
stress by changing physiological functions even when there is
no visible cell injury or cell lysis.

Thus, different scale up rules (constant P/V implies constant


OTR, Constant Re implies geometrically similar flow patterns,
constant N to give constant mixing times and constant tip
speed to give constant shear) can give very different results.

These scale-up problems are all related to transport


processes. In particular, the relative time scales for mixing and
reaction are important in determining the degree of
heterogeneity in a fermenter.
As we scale up, we may move from a system
where the microkinetics (the cellular reactions)
control the system response at small scale to
one where transport limitations control the
system response at large scale. When a change
in the controlling regime takes place, the results
of small-scale experiments become unreliable
with respect to predicting large scal
performance.
Traditional scale-up is highly empirical and makes
sense only if there is no change in the controlling
regime during scale-up, particularly if the system is only
reaction or only transport controlled.

Common scale-up are the maintainance of constant


power-to-volume ratios, constant Kla, constant tip
speed, a combination of mixing time and Renolds
number, and the maintanance of the constant substrate
or product level (usually dissolved-oxygen
concentration). Each of these rules has resulted in both
succesful and unsuccesful examples. Results are more
favourable with Newtonians broths than with non-
Newtonian systems.
After a batch fermentation, the system is
dismantled and approximately 75% of cell mass
is suspended in the liquid phase of 2L, while 25%
is attached to the reactor walls and internals in a
thick film (0.3cm). Work with radioactive tracers
shows that 50% of the target product
(intracellular) is associated with each cell
fraction. The productivity of this reactor is 2 g/L at
2L scale. What would be the productivity at
20000 L scale if both reactor had a height-to-
diameter ratio of 2 to1?
Consider the scale up of a fermentation from 10L to 10000L
vessel. The small fermenter has a height-to-diameter ratio of
3. the impeller diameter is 30% of the tank diameter. Agitator
speed is 500 rpm and three Rushton impellers are used.
Determine the dimensions of the large fermenter and agitator
speed for:

a. Constant P/V
b. Constant impeller tip speed
c. Constant Reynolds number