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Principles of Biochemical
Engineering
ENCH 535 Winter 2016
Bioreactor Scale Up
Scale up of bioreactors
Reactor dimension
3/30/2016
Submerged
cultures
Stirred tank
Airlift
Immobilized
cultures
Bubble
columns
Reactor types
Packed bed
Fluidized
beds
Airlift
Stirred tank
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Reactor types
Figures source:
Bubble-Column
http://en.wikipedia.org/wiki/File:Bubble_column.svg
http://www.algaeindustrymagazine.com/algae-scale-up-bioreactors-from-biovantage-resources-inc/
Reactor types
Air-lift
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ORP, pH
probes
Recirculation
pump
Water-jacketed
glass reactor
carrier
Glass
beads
wastewater
3/30/2016
Scale-up issues
A scale-up problem is something that we do not see in the
small-scale experiment and are surprised and disappointed
to find in the large scale process
Heat transfer
Mass transfer (oxygen)
Power input
Foaming
Sterility
Product quality
By-product formation
3/30/2016
Scale-Up Parameters
Geometry
Height to Diameter Ratio is held constant
Called aspect ratio
Scale-Up Parameters
Agitation-based parameters
Mixing time
Power input per Volume (P/V)
Tip Speed
Gassing-based parameters
Vessel Volumes per Minute (VVM)
Superficial Gas Velocity (Vs)
NOTE: Cannot keep all parameters constant during scale
up because they scale by different values
3/30/2016
Parameter
Definition
Scale-Up Factor
Importance
N2=N1(D1/D2)1/4
Mixing time
Amount of power
transferred to a volume of
cell culture through the
agitator shaft and impellers
P/V N3/D2
P- power supplied
V- Volume of Bioreactor
N- Agitation Speed
D- Impeller Diameter
N2=N1(D1/D2)
Tip speed
Superficial gas
velocity (Vs)
Vessel Volume
per minute (vvm)
Vs = Qgas/Av
Vs- superficial gas velocity
Qgas- gas volumetric flow rate
Av- inside cross-sectional area of
vessel
Volume of Gas Flow/ ( time x
Reactor volume)
Symbol Small
scale (80L)
P0 /V
Energy input
P0
1.0
125
3125
25
0.2
Energy input/volume
P0/V
1.0
1.0
25
0.2
0.0016
Impeller rotation
1.0
0.34
1.0
0.2
0.04
Impeller diameter
Di
1.0
5.0
5.0
5.0
5.0
1.0
42.5
125
25
5.0
Pump rate of
impeller/volume
Q/V
1.0
0.34
1.0
0.2
0.04
N Di
1.0
1.7
5.0
1.0
0.2
Reynolds number
NDi2/
1.0
8.5
25.0
5.0
1.0
Table source:
3/30/2016
Scale-up Strategies
Rules of thumb:
Rigorous simulation:
Not always possible
Experimental data needed for validation
3/30/2016
CFD
Definition: Numerical solution (computer simulation) of differential equations
describing fluid flow, heat, mass, and momentum transfer, chemical reactions.
Advantages
Disadvantages
Heat Transfer
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Mixing
Mixing is the achievement of uniformity
Purpose:
Blending: substrate, pH control
Suspending: solid particles, immobilized cells
Dispersing: two liquid phases, aeration
Marine propeller
Lightnin A310
10
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11
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Foaming
Foam is a natural byproduct mostly protein
bubbles but some lipids
Foam will block and wet filters causing pressure
back-up and contamination
Foam must be controlled by chemical dispersing
agents (antifoams) or mechanically broken
Maintaining 75% volume capacity of reactor
allows for foam to be retained within the vessel
Sterility
Sterilization in place (SIP)
cleaning of reactor and bed
without dismantling reactor or
feed tubes
Pressurized steam is used for inplace sterilization of probes,
valves and seals
All crooks, crevices and surfaces
are potential contaminants and
must be sterilized
Sterilization must be verified and
validated
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