Scale­up 

1. In scaling up a bioprocess using Penicillium (a mold) the power input per unit
reactor volume is to be kept constant to ensure proper dispersion of mycelia. The
reactor is scaled up geometrically similarly from 10 liters to 1000 liters.
a. What will happen to the agitation rate in the scaling up process?
b. What happens to the impeller tip speed?
c. The “pumping” of liquid can be estimated by the area moved by the impeller
blade’s rotational movement and the rotation speed. How will you represent
pumping using N and Di? How will pumping be affected by scaling up?

2. In the small bioreactor of 10 l, air is supplied at 10 l per minute [thus at 1 vvm

(volume/volume – minute)]. The air inlet and outlet oxygen concentration is 21%
and 19% respectively. In scaling up to 1000 l, the superficial velocity is kept
constant. Assuming the oxygen demand of the culture remains constant, what
will the outlet oxygen concentration be? If the respiratory quotient is one,
compare the CO2 concentration at the outlet of the gas stream in the small scale
and large scale. You can neglect the evaporation of water and the effect of
hydrostatic pressure.

3. Metabolic heat generated during microbial growth needs to be removed by

cooling water in most fermentation processes. Discuss why heat removal can be a
problem in scaling up. Note: typically the cooling of bioreactor is accomplished
by using a water jacket on the wall and by water cooling coils inside the reactor.

4. In non-Newtonian, mycelial fermentations there is a substantial resistance to oxygen

transfer between the bulk liquid and the mycelial clumps. Furthermore, the impeller tip
speed (T = ÐNDi where T = impeller tip speed, N = impeller rotational speed and Di =
impeller diameter) has been shown to be directly proportional to the liquid to clump mass
transfer coefficient. This finding appears to offer an excellent method for process scale-
up, process translation, or fermentor design. You have been asked to consider the
following two cases (A and B) with respect to scale-up of large fermentor operations.

a) You have the option of designing the large scale fermentor in one of two ways. The
total liquid volumes (VL) and the agitator power per unit volume as well as the ratio for
impeller diameter to tank diameter (Di/DT) are also to be maintained the same in the two
options. The liquid height (HL) as is

HL = 2 nDi

where HL = liquid height

n = number of agitators
Di = impeller
You may design a tall fermentor with 3 agitators (n = 3) or a shorter fermentor with 2
(n=2) agitators. If you are to maximize the mass transfer to the clump which approach
will you take? How do the two options differ?

b) A large size fermentor of a given volume and its motor already exist. You are to
consider the two cases of different diameters of the impeller. However, for simplicity the
number of agitators on the shaft for both cases can be considered to be equal.

If your objective is again to maximize mass transfer from liquid to clump using the
constraints stated, show whether you should design for smaller or larger impeller sizes
and how they differ.

For simplicity, you may assume the following:

1) The impeller Reynolds Number is in turbulent regime and the fluid behaves
essentially Newtonian at this condition.

2) Neglect the aeration effect on power drawn by the impeller.

5. The mean mixing time in a bioreactor has been estimated to be inversely proportional
to the agitation rate when the bioreactor is scaled up geometrically similarly. If the power
input per unit volume is to be kept constant, what will happen to the mean mixing time
when scaling up?

6. Scale-up of stirred tank. A 1 m3 reactor is to be scaled up 125-fold geometrically

similarly. Some operating conditions of the 1 m3 fermentor are shown below. Both
fermentors are to be operated basically in the turbulent regime with an impeller Reynolds
number greater than 104. The power number can be assumed to be a constant value of
6.5. In both cases the gassed power can be assumed to be 0.6 of ungassed power. The
gassed power input per unit liquid volume will be maintained constant in the scaling up.

Operating conditions of the 1 m3 reactor:

air flow rate: 1 m3/min

exit oxygen partial pressure: 0.17 atm
inlet oxygen partial pressure: 0.21 atm
flooding gas flow rate: 3 m3/min
agitation rate: 120 rpm

Correlation for Kla: The equation should read

KLa(1/hr) = A(Pg/V)0.5Vs0.
The flooding superficial velocity is the same in both reactors. However, in the large
reactor the gas flow rate will be in the range of 0.5 to 0.7 of flooding gas velocity
as opposed to 0.333 in the 1 m3 fermentor. It is desired that the dissolved oxygen
concentration in the large tank be maintained at the same level as the small tank at
0.03 atm of PO2 (or 0.03 mM).

a) What is the agitation rate in the large fermentor?

b) Design the large fermentor with the same value of KLa. What you have to do to gas
flow rate What is the oxygen transfer rate?

c) How do you achieve the same oxygen transfer rate? What are the KLa and the gas
flow rate?

In solving problem, neglect the hydrostatic pressure effect.