1. Chapter 5: BIOREACTOR DESIGN & SCALE-UP

2. Types of Impellers

3. Mixing
Please read the reading material given.

4. Data Required for Bioreactor Selection and Design
Microorganism species
Growth and oxygen requirements
Shear and rheology effects
Sterility
Volumetric output
Light
Foam
Final use
Cleaning and sterilizing
Heating and cooling
Materials of construction
Measurement Systems

5. Definition of Scale Up
The successful startup and operation of a commercial size unit whose design and operating procedures are in part based upon experimentation and demonstration at a smaller scale.
The purpose of scale up is the selection design conditions and operational procedures to ensure that the effect of the different variables on the process is the same in units of different size.
Also to obtain similar yield.

6. Scale up Procedure
1. Similar Reynolds number or momentum factors. 2. Constant power consumption per unit volume of liquid, Pg/V 3. Constant impeller tip velocity, NDi 4. Equal mixing and recirculation time, tm 5. Constant mass transfer coefficient, KLa

7. Design for Stirred Tank Design
Height:Diameter ratio between 2:1 to 6:1
Fitted with baffles
4 baffles (6-8 in) if the tank diameter is less than 3 m
6-8 baffles if the tank diameter larger than 3m
Width of baffles, T/10 and T/12
Diameter of vessel to baffle 10 < Dt/Db < 12
75% of the total vessel volume is filled with liquid, 25% is for gas space. If foaming takes place, there is no chance of immediate contamination.
If H=D, one agitator is enough
If H=2D or more, additional set of agitator should be added.
Proper spacing between impellers should be Di < Hi < 2Di
Installation of multiple sets of impellers improves mixing and mass transfer.

8. Design for Stirred Tank Design
Spargers should always be located near the bottom of the vessel with a distance Di/2 below the impeller.
Power input per unit volume of fermentation vessel for a normal fermenter should be greater than 100W/m3.
Impeller tip speed (πNDi) should be greater than 1.5 m/s. Antifoam cannot always be added for the foam reduction due to inhibitory effect. So the simplest devices have rakes mounted on the stirrer shaft and located on the surface of the fluid.
If heat removal is a problem, in large bioreactors greater than 100 m3, up to 12 baffles can be used, through which coolant passes.
For efficient mass transfer, a multiple orifice ring sparger with a gas outflow diameter of 3Di/4 is used.
There should be minimum number of openings so that sterility can be maintained. Small openings must be made leak-proof with an O-ring, larger openings with gaskets.

9. Constant Power per Unit Volume
P/V determines the Reynolds number value
NDi determines the maximum shear stress
When the fluid in the tank is full turbulent, the power number is constant
P  N3Di5
P/V  N3Di2
(N3Di2)1 = (N3Di2)2

10. Example 1
A bacterial fermentation was carried out in a bioreactor containing broth with average density ρ=1200 kg/m3 and viscosity 0.02 N.s/m2. The broth was agitated at 90 rpm and air was introduced through the sparger at a flow rate of 0.4 vvm. The bioreactor was equipped with 2 sets of flat blade turbine impellers and 4 baffles. The dimension of vessel, impellers and baffle width were:
Dt = 4 m
Di = 2 m
Wb = 0.4 m
H = 6.5 m
Determine (a) ungassed power, P
(b) gassed power, Pg
(c) KLa
(d) gas hold up