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R7.2 Fermentation Scale-up

  Scale-up for the growth of microorganisms is usually based on maintaining a constant dissolved oxygen concentration in the liquid (broth), independent of reactor size. Guidelines for scaling from a pilot-plant bioreactor to a commercial plant reactor are shown in Table R7.2-2.

One key to a scale-up is to have the speed of the end (tip) of the impeller equal the velocity in both the laboratory pilot reactor and the full-scale plant reactor. If the impeller speed is too rapid, it can lyse the bacteria; if the speed is too slow, the reactor contents will not be well mixed. Typical tip speeds range from 5 to 7 m/s.

This scale-up procedure has been applied11 to the data of Rogovin et al.12 to produce 205,000 kg of Phosphomannan per year using the yeast Hansenula holstii. The pilot reactor was 2.3 m3 (600 gal) and the plant reactor was 50 m3(13,200 gal). The relative sizes of the scaling groups for this plant are shown in Table R7.2-3.

Perspective. In the limited space available for this topic we have presented this greatly simplified version of bioreactor design. Here we have tried to give an overview of some of the basic ideas and vocabulary that will serve as a springboard to a deeper study of bioreaction engineering. For example, we have considered only a single nutrient source and have not discussed the interrelated enzymatic reaction pathways that exist between all the species necessary for cell growth. Wang et al.13 and Bailey and Ollis14 discuss the finer and more intricate details associated with the use of microorganisms to produce chemicals, antibiotics, and food products. In addition to the fundamentals already known about bioreactors, many challenging research areas exist. For example, animal cells are fragile and very susceptible to being lysed (killed) by even moderately large shear stress. Consequently, scale-up and thorough mixing of cells, nutrients, and oxygen become extremely difficult problems. In addition, cells can aggregate, which poses the problems of maintaining a supply of nutrients and removal of wastes. Fundamental studies of flocculation and surface interactions of microorganisms will aid in the solution to the aggregation problem as well as explore other frontiers of bioreactors, thus providing stimulating research in this area for many years to come.
     
   

TABLE R7.2-2



 

1. Choose fermenter volume required based on desired capacity.

Algorithm for fermentor

IMAGE 07eq130.gif

2. Choose impeller diameter, Di.
3. Calculate reactor dimension (e.g., DT = tank diameter) based on geometric similarity, with the impeller diameter being the characteristic length, for example,

IMAGE 07eq130a.gif


Alternatively, we could have chosen the tank diameter, DT, in step 2 and then used Equation (A) to calculate the impeller diameter, Di.
4. Calculate impeller speed, N.

(pi.gifDiN)PLANT = (pi gifDiN)AB

Then

image 07eq130c.gif

5. Choose mass transfer correlation for kbab.
6. Calculate gas flow rate using the correlation and setting

(kbab)PLANT = (kbab)LAB


For example, from Equation (CD7-51) the mass transfer coefficient kLab depends on the following equipment parameters

image 07eq130d.gif


Then

IMAGE 07eq130e.gif



7. Calculate power requirement.
7A. An alternate (2) procedure for determining N and Q is to set either Q/ND = constant or
VS = constant and then determine N from power or mass transfer correlations. These and other techniques, such as keeping the power per unit volume a constant, are discussed in Baily and Ollis.*


* T. J. Bailey and D. Ollis, Biochemical Engineering, 2nd ed., McGraw-Hill, New York, 1987.


TABLE R7.2-3
PHOSPHOMANNAN FERMENTATION SCALEUP*
IMAGE 07eq131.gif



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