Scale-Up Problems Mold

Scale up 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 movement and the rotation rotation speed. How will you represent represent pumping using N and D i? How will pumping pumping be affected affected by scaling up? 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 CO 2 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 scaleup, 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 (V L) and the agitator power per unit volume as well as the ratio for impeller diameter to tank diameter (D /D i T) are also to be maintained the same in the two options. The liquid height (H L) 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? 3

6. Scale-up of stirred tank. A 1 m reactor is to be scaled up 125-fold geometrically 3 similarly. Some operating conditions of the 1 m fermentor are shown below. Both fermentors are to be operated basically in the turbulent regime with an impeller Reynolds 4 number greater than 10 . 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. 3

Operating conditions of the 1 m reactor: air flow rate: exit oxygen partial pressure: inlet oxygen partial pressure: flooding gas flow rate: agitation rate:

Correlation for Kla: The equation should read 0.5

0.

KLa(1/hr) = A(Pg /V) Vs

3

1 m  /min 0.17 atm 0.21 atm 3 3 m  /min 120 rpm

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 3 as opposed to 0.333 in the 1 m 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 K La. 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 K La and the gas flow rate? In solving problem, neglect the hydrostatic pressure effect.