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Publicado: 3 de diciembre de 2012
SELECTION, SCALE-UP AND SCALE-DOWN OF BIOREACTORS
Why is scale-up a challenge?
•
Difficult to maintain homogeneity on large scale.
- Bugs experience gradients at large scale: temperature,
O2dissolved concentration,
pH,
substrate.
- Culture has more pressure to mutate with number of divisions.
- Phage contamination can occur.
- Use of industrial-grade nutrients.
- Changes in mediumdue to length of sterilization time.
•
It is important to do optimization experiments in a similar fashion to the largescale system.
•
Reactor selection should be based on commercial scaleeconomics.
•
"Scale-down" experiments.
Reactor Selection
1. Stirred Tanks
2. Bubble Columns (sparged column)
3. Loop Reactors
a. Airlift
liquid motion induced by flow of gas.
b. Loopwith mechanical agitation.
Three-phase reactors (gas - liquid - solid) are difficult to predict with first principles
models.
1) Stirred Tanks
- Advantages over bubble column and airlift:
-Flexibility (if they have a variable speed motor).
- Can provide high kLa (high oxygen mass transfer).
For non-viscous (< 30 cP) aerobic fermentation, k L a > 600 / hr
(corresponds to an OUR of ~ 120 mM/hO2), you need a stirred tank.
Note: Archer-Daniels Midland runs stirred tank fermentors 130,000 gal in size.
- Disadvantage is operating cost.
- Operation:
Gas under pressure is sent inthrough a sparge ring just below the bottom impeller
(want very small bubbles)
Drive Motor
Placement of impellers is very
important. If the tank is empty to
start, and liquid fills it, there will bea
variation in P(w)/m (power per unit
mass) over time during the run.
Effluent Gas
Baffles
(4)
Water out
Turbine Agitator
Water in
Inlet Air
Rushton Impellers are radial flowimpellers. Marine impellers are axial flow (also
pitched blade). Most efficient configuration is to have an up-pumping impeller near the
bottom of the tank.
Baffles are also necessary for good mixing....
Why is scale-up a challenge?
•
Difficult to maintain homogeneity on large scale.
- Bugs experience gradients at large scale: temperature,
O2dissolved concentration,
pH,
substrate.
- Culture has more pressure to mutate with number of divisions.
- Phage contamination can occur.
- Use of industrial-grade nutrients.
- Changes in mediumdue to length of sterilization time.
•
It is important to do optimization experiments in a similar fashion to the largescale system.
•
Reactor selection should be based on commercial scaleeconomics.
•
"Scale-down" experiments.
Reactor Selection
1. Stirred Tanks
2. Bubble Columns (sparged column)
3. Loop Reactors
a. Airlift
liquid motion induced by flow of gas.
b. Loopwith mechanical agitation.
Three-phase reactors (gas - liquid - solid) are difficult to predict with first principles
models.
1) Stirred Tanks
- Advantages over bubble column and airlift:
-Flexibility (if they have a variable speed motor).
- Can provide high kLa (high oxygen mass transfer).
For non-viscous (< 30 cP) aerobic fermentation, k L a > 600 / hr
(corresponds to an OUR of ~ 120 mM/hO2), you need a stirred tank.
Note: Archer-Daniels Midland runs stirred tank fermentors 130,000 gal in size.
- Disadvantage is operating cost.
- Operation:
Gas under pressure is sent inthrough a sparge ring just below the bottom impeller
(want very small bubbles)
Drive Motor
Placement of impellers is very
important. If the tank is empty to
start, and liquid fills it, there will bea
variation in P(w)/m (power per unit
mass) over time during the run.
Effluent Gas
Baffles
(4)
Water out
Turbine Agitator
Water in
Inlet Air
Rushton Impellers are radial flowimpellers. Marine impellers are axial flow (also
pitched blade). Most efficient configuration is to have an up-pumping impeller near the
bottom of the tank.
Baffles are also necessary for good mixing....
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