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SCALE UP

FACTORS
FACTORSTO
TOBE
BECONSIDERED
CONSIDEREDIN
INSCALING
SCALINGUP
UPBIOREACTORS
BIOREACTORS
CONSTANT POWER INPUT PER UNIT VOLUME
(P/V = constant)

From the work of Rushton and his associates, for


geometrically similar, fully baffled vessels with turbulent
conditions, it may be noted that if scale up should be based
on maintaining a constant power input per unit volume
considering no gassing in the system.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

FACTORS
FACTORSTO
TOBE
BECONSIDERED
CONSIDEREDIN
INSCALING
SCALINGUP
UPBIOREACTORS
BIOREACTORS
CONSTANT POWER INPUT PER UNIT VOLUME
(P/V = constant)
NON-GASSED
SYSTEM

SCALED
UP

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

FACTORS
FACTORSTO
TOBE
BECONSIDERED
CONSIDEREDIN
INSCALING
SCALINGUP
UPBIOREACTORS
BIOREACTORS
CONSTANT POWER INPUT PER UNIT VOLUME
(P/V = constant)
GASSED
SYSTEM

SCALED
UP

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

FACTORS
FACTORSTO
TOBE
BECONSIDERED
CONSIDEREDIN
INSCALING
SCALINGUP
UPBIOREACTORS
BIOREACTORS
Constant Mass Transfer Coefficient, KLa

There has to be a relation between Kla with aeration rate and


agitation speed, and scale-up factor has to be determined. To
eliminate the effect of viscous forces, the rheology of the
media and broth for a large vessel have to be similar to
that of a bench-scale vessel.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

FACTORS
FACTORSTO
TOBE
BECONSIDERED
CONSIDEREDIN
INSCALING
SCALINGUP
UPBIOREACTORS
BIOREACTORS
Constant Mass Transfer Coefficient, KLa

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

FACTORS
FACTORSTO
TOBE
BECONSIDERED
CONSIDEREDIN
INSCALING
SCALINGUP
UPBIOREACTORS
BIOREACTORS
Constant Mixing Quality

Constant mixing quality in otherwords indicates constant


Reynolds number, NRe.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

SAMPLE
SAMPLEPROBLEM
PROBLEM
Consider the scale-up of a fermentation from a 10L to 10,000L
vessel. The small fermenter has a height-to-diameter ratio of 3.
The impeller diameter is 30% of the tank diameter. Agitator
speed is 500 rpm and three Rushton impellers are used.
Determine the dimensions of the large fermenter and agitator
speed for Constant P/V.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

SAMPLE
SAMPLEPROBLEM
PROBLEM
Assume the vessel is a cylinder, ;
H = 3Dt;
Dt = 16.2 cm
H = 48.6 cm
Di = 4.9 cm

The scale-up factor is the cube root of the ratio of tank volumes,

(10,000L /10 L)1/3 = 10 Dt = 1.62 m


H = 4.86 m
Di = 0.49 m
CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

SAMPLE
SAMPLEPROBLEM
PROBLEM
For constant P/V to apply N^3Dt^2 must be the same in both
vessels.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

SAMPLE
SAMPLEPROBLEM
PROBLEM
A value of KLa 30 per hour has been determined for a fermenter
at its maximum practical agitator rotational speed and with an
being sparged at 0.5 1 gas/liter reactor volume—min. E. coli
with a qO2 of 10 mmol/2/g dry weight are to be cultured. The
C, is 0.2 mg/l. The solubility of O2 from air in the fermentation
broth is 7.3 mg/l at 30˚C, 0.21 atm.
a) What maximum concentration of E.coli can be sustained in
this bioreactor under aerobic conditions,
b) What concentration could be maintained if pure O2 was used
to sparged the bioreactor?‘
CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

SAMPLE
SAMPLEPROBLEM
PROBLEM At steady state, dCl/dt = 0;

0.21 atm gives 7.3mg/l of solubility


 

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

FACTORS
FACTORSTO
TOBE
BECONSIDERED
CONSIDEREDIN
INSCALING
SCALINGUP
UPBIOREACTORS
BIOREACTORS
Constant Impeller Speed

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. Typical tip speeds range from 5
to 7 m/s indicating the predominant importance of this
parameter in scale up.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

FACTORS
FACTORSTO
TOBE
BECONSIDERED
CONSIDEREDIN
INSCALING
SCALINGUP
UPBIOREACTORS
BIOREACTORS
Constant Impeller Speed

The peripheral tip velocity, Vt , of the


impeller diameter Di, and the
rotational speed n (s-1) is given by:

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

FACTORS
FACTORSTO
TOBE
BECONSIDERED
CONSIDEREDIN
INSCALING
SCALINGUP
UPBIOREACTORS
BIOREACTORS
Impeller Reynold’s Number

This criterion is used sometimes when the heat transfer rate


from the fermentation broth to the cooling coils inside the
bioreactor vessel is of paramount importance. This is especially
important for thermophilic microorganisms. The heat transfer
coefficient is a function of impeller Reynold‘s number.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
SCALE UP

FACTORS
FACTORSTO
TOBE
BECONSIDERED
CONSIDEREDIN
INSCALING
SCALINGUP
UPBIOREACTORS
BIOREACTORS
Impeller Reynold’s Number
For this scale up criterion,
the impeller Reynold‘s
number must be equal for
the small and large scale
bioreactor, constant r, m.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
OPERATION AND
CONTROL
.
OPERATION AND CONTROL

The growth of an organism in a bioreactor


has to be controlled, so the operators must
have sufficient information about the state
of the organism and the bioreactor
conditions. Monitoring a fermentation
process may need basic knowledge of the
bioprocess, and the running conditions
should be recorded.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
OPERATION AND CONTROL

There are many types of bioreactor used in


bioprocesses such as the continuous
stirred tank reactor (CSTR), plug flow
column, bubble column bioreactor, etc. The
most common form is the simple stirred
tank bioreactor.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
OPERATION AND CONTROL
In bioprocess
plant
instrumentation
and process
control, variables
are very
important.

The main
objective is to
operate a
bioreactor
without any
problems.
CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
OPERATION AND CONTROL
TEMPERATURE
Control of temperature for fermentation
vessels is required because of the narrow
range of optimal temperature.

To maintain bioreactor temperature within


the limited range, the system may require
regulation of heating and cooling by the
control system.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
OPERATION AND CONTROL
TEMPERATURE TEMPERATURE CONTROL
DEVICES
THERMOCOU
PLE cheap and simple to use, but they are rather 
low in resolution and require a cold junction

THERMIST
ORS are semiconductors, which exhibit a change 
in electrical conductivity with temperature.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
OPERATION AND CONTROL
DISSOLVED
OXYGEN The dissolved oxygen content of the
fermentation broth is also an important
fermentation parameter, affecting cell
growth and product formation.

The low solubility of oxygen makes the


measurements very difficult, a challenging
problem

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
OPERATION AND CONTROL
DISSOLVED
OXYGEN
DISSOLVED OXYGEN
TUBIN
DETERMINATIONan  inert  gas  flows  through  a  coil  of 
G
permeable  silicon  rubber  tubing,  in  which 
METHO the oxygen from the reactor flows through 
D
MASS
SPECTROMETRY
ELECTROCHEMICAL
DETECTORS
Two  types  of  detector  are  commercially  available: 
galvanic  and  polarographic  detectors.  Both  use 
membranes  to  separate  electrochemical  cell 
components from the broth. 
CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
OPERATION AND CONTROL
PH
The fermentation process is normally
carried out at a constant pH. The pH of a
culture medium will change with the
metabolic product of microorganisms, which
are developed in the fermentation media.

Measurement of pH is based on the absolute


standard of the electrochemical properties of
the standard hydrogen electrode.

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
OPERATION AND CONTROL
FOAMING
In a gas and liquid system, when gas is
introduced into a culture medium, bubbles
are formed, forming froth.

During fermentation, foaming may occur


suddenly. Some foams are easy to destroy
and can be removed by foam breaker; others
are quite stable and are relatively hard to
BIOREACTOR remove from the top of the bioreactor.
SENSORS

CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
OPERATION AND CONTROL
FOAMING FOAMING CONTROL
MECHANIC
OPERATION
AL
mechanical agitation such as a foam breaker, operates on 
the center of the shaft. They are generally blades or disks 
that are mounted on the same agitator shaft. 

CHEMICAL
Chemical  anti-foams  are  used  to  regulate  the  foam  and 
prevent  any  foaming  on  the  surface. The  chemical  anti-
foams are expensive and minimal amounts must be used. 
CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |
OPERATION AND CONTROL
BIOSENSORS A biosensor consists of two main elements.
These two elements, the biocatalyst and a
transducer, are combined as a single
detecting probe, in which the transducer
and biocatalyst are held together in a very
close contact.
measures the biochemical transformation of a
BIOCATALYST given substance, for example change in pH

detect such change and to produce an output


TRANSDUCER signal, which is related to the concentration of
the measured substance.
CHE 512: BIOCHEMICAL ENGINEERING | BIOREACTOR SELECTION, SCALE UP, OPERATION, AND CONTROL |