Quiz

Materials:

CHNG 3804 & 4501

Bio-Reactor Design Oxygen
Transfer and Heat Transfer

All the lectures from week 1-week 6

All the articles and supplementary documents
given so far.

Maximum two hrs close book quiz

The questions include

True and false questions that should be corrected

if they are wrong
Short answers questions
Problems similar to the one given for tutorials.

Know how to use the calculator for linear

regression.

BioBio-Reactor Design Oxygen Transfer

and Heat Transfer
Oxygen Transfer Rate
Fundamentals
Practical Considerations
Heat Transfer
Fundamentals
Practical Considerations
Importance of Broth Rheology
Link between OTR and Heat Transfer
Design Problem

The solubility of Oxygen in water is low.

Pure water at 25C, 8ppm O2 (8mg/L)
Can vary with media components and microorganism
concentration

Need to consider mass transfer from the oxygen

in the bubbles to the dissolved oxygen in the
broth.
Generally use a lumped parameter to account
for the mass transfer coefficient and the surface
area of the bubbles

Oxygen Transfer - Theory

OTR = kl a CO2 CO2

Oxygen Transfer - Theory

Where

CO2 is the actual dissolved oxygen concentration

CO2

is the dissolved oxygen concentration in equilibrium with

the existing PO2 in the gas

kla is a lumped parameter incorporating the mass transfer

coefficient and the surface area of the bubbles

Bubble Size
Smaller bubbles give greater surface area per
volume
Smaller bubbles also have slower rise velocities
kl is relatively constant above 2-3 mm
Below 2-3mm kl decreases with bubble size
Bubbles < 1mm can cause problems
Surface tension effects start to dominate
Bubbles behave as rigid spheres

Gas HoldHold-up
Defined as

Oxygen Transfer kla determination

There are published correlations

VG
VG + VL

Generally determined on small lab fermenters

kla can be determined experimentally

The total interfacial area depends on the

total volume of gas in the system
Hold up values are difficult to predict and
range from 0.01 to 0.2
A significant fraction of the oxygen in a
fermenter is present in the held up bubbles

kla often varies during batches

Probable causes are changes in broth rheology
due to substrate depletion or microbial growth.

VG: volume of the gas, VL: Volume of the liquid

Dynamic measurement of kla

Local steady state

Assume :

_
C
C2

CO2

air off

C B >> K B
etc
dSO 2

C1

dt

t2

dSO 2
dt

High oxygen concentration

dSO 2
dt

dt

max x
YX / O 2

dSO 2

CO2
max
x
YX / O 2 K O 2 + C O 2

CO2
max x
YX / O 2 K O 2 + C O 2

Dynamic measurement of kla

During the re-oxygenation step, the system is not at
steady state. The rate of change in dissolved oxygen
concentration is equal to the rate of oxygen transfer
from gas to liquid, minus the rate of oxygen uptake
by the cell. dC
= k l a (C * C ) q 0 x
dt
Is the rate of oxygen consumption
q0 x

Before switching air off :

dC O 2

At local steady state (small t) :

dx
0
dt

air on
t1

1 dX
1 dP
dS
=
mX
dt
YX / S dt
YP / S dt

C A >> K A

_
CAL

q 0 x = k l a (C * C )

= max = k O 2 a CO 2 CO 2
dt
YX / O 2

dC
dt

= k l a (C C )
ln(

kl a =

C C1
)
C C2
t 2 t1

Dynamic measurement of kla

Switch air back on :
dCO 2
= k O 2 a CO 2 C O 2 k O 2 a CO 2 CO 2
dt
dCO 2
= k O 2 a CO 2 C O 2
dt
dCO 2
C2
t2
= k O 2 a dt
C1 C
t1
O2 C O 2
ln
k O2 a =

Dynamic measurement of kla

)
ln

CO 2 C1

CO 2 C 2

CO 2 C1

slope = kla

CO 2 C 2
t 2 t1

t 2 t1

Specific oxygen uptake rate (SOUR)

SOUR x

After switching air off :

dC O 2

dSO 2

=
= max = k O 2 a CO 2 CO 2
dt
dt
YX / O 2

ln(SOUR)
ln(x)

t
Generally find a good relationship between Cell density or growth
rate and OUR

Oxygen Limitation
Insufficient oxygen supply can
limit fermenter productivity
result in the formation of inhibitory byproducts
For example with E.coli insufficient oxygen supply
can result in the formation of acetic acid
Acetate is inhibitory to both growth and product
formation.

Increasing OTR
Mass transfer is increased by:
Large concentration difference between phases
Large surface area (small bubbles)
Turbulent flow (high bubble velocity)

Increasing OTR

Pressure
Oxygen Enhancement
Gas Flow
Agitation

Pressure and OTR

Increasing the pressure increases the partial pressure of
the oxygen and hence the equilibrium liquid
concentration
Fermenters are built to withstand pressure for
sterilisation etc
Can generally increase the OTR by increasing fermenter
pressure to near fermenter design pressure
Effective and relatively inexpensive method to increase
OTR
Generally not economic if fermenter wall thickness
needs to be increased adds to cost and reduces heat
transfer.
Some organisms are sensitive to pressure/CO2

Oxygen Enrichment and OTR

Increases OTR due to increased partial
pressure
Useful in labs
particularly if organism is pressure
sensitive

Expensive and potentially hazardous at

large scale

Gas Flow and OTR

Increasing gas flow increases both the value of kla
and the mass transfer driving force.
Rule of thumb with small to medium fermenters is a
gas flow rate equal to the fermenters volume each
minute.
Doesnt hold for larger fermenters
Increasing gas flow increases the effect of foaming
Increased gas flow can result in flooding of the
impeller

Agitation and OTR

Increased agitation increases the OTR by
reducing the diameter of bubbles.
This results in greater power dissipation in
the fermenter.
Increasing the heat removal requirements
Many organisms are shear sensitive
Poorly understood,
Some rules based on impeller tip speed,
others on rpm

Example
What is the effect on oxygen mass transfer
to a CSTR of halving the air bubble
diameter, all other things equal?

Example (continued)
For the same volume of gas, decreasing the
bubble diameter increases the total surface
area available (because the interfacial
surface area to volume ratio increases)

a=

area
4r 2
3
3
6
=
= =
=
volume 4 r 3 r d / 2 d
3

Empirical correlations for mass

transfer
kl = f (v, d, other rheological properties)
where:
v = velocity (LT-1) of agitator, fluid, bubbles
d = diameter (L) of bubbles, agitator

Empirical correlations for mass

transfer
What is the effect on oxygen mass
transfer to a CSTR of doubling the
impellor speed, assuming negligible
effect on bubble size?

The relationship between k and v, d is not

linear!

Empirical correlations for mass

transfer

Empirical correlations for mass

transfer from power input

For high Re :
1/ 3

Sh l 1.1Sc l

Rel

0.6

kl a = 2.0 103

N1 k1a1C1 k1 Sh1D1 d1 Sh1

=
=
=
=
N 2 k 2a 2 C 2 k 2 Sh 2 D 2 d 2 Sh 2
13

0.6

Sc Re
vd
= 11 3 1 0.6 = 1 1 1 1
2 v 2d 2 2
Sc 2 Re2

0.6

v
= 1
v2

0.6

0.6

1
= 0.66
2
N 2 = 1.52 N1
=

Notes on the Previous Correlation

Obtained using with water containing ions.

Volumes from 20L to 4.4m3.
500 < P/V < 10000 (W/m3)
Accurate to 20-40% within this range
Independent of agitator type.
Has been found to over-predict mass
transfer by 100% at 25 m3.

P
V

0.7

vg

0 .2

where :
P = power input (W)
V = reactor volume (M3 )
v g = superficial gas velocity (M s -1 )

Consequences of Increasing OTR

Foaming
Air flowing through a fermenter can cause the
formation of foam
The severity of the foam is dependent on
media, microorganism and air flow rate

Increased Heat Transfer Requirements

Increasing agitation results in increased heat
dissipation, hence increased requirement for
heat removal
Aerobic metabolism

Foam
Two methods for treating
foam
Mechanical foam breaker
High speed impeller

Antifoam surfactants

Adapted from Ref. 1

Metabolisable
Non-metabolisable
May reduce mass transfer
rates

Heat Removal
Q=UAT
Heat transfer is proportional to the
temperature driving force or temperature
difference and the interfacial area
Increase heat transfer by:
decreasing temperature of the cooling fluid
increasing interfacial area in cooling jackets
increasing flowrate of cooling fluid

Stirred Tanks
In CHNG 3801 we briefly looked at heat transfer in
stirred tanks
The cooling/heating can be accomplished by
External Jacket Heat transferred through vessel
wall
Limpet Coils Heat transferred through vessel
wall
Internal Coils - Heat transferred through coil wall

Heat Generation
Sources of heat generation in fermentations
include viscous shear in turbulent mixing
and aerobic respiration
In aerobic fermentations, the rate of heat
generation due to respiration is 460 kJ per
mole oxygen consumed
The rate of heat generation in a large
fermenter can be calculated from the heat
duty of the cooling fluid

Heat Transfer
1 1 t 1
1
1
= + + +
+
U hi k ho h fi h fo
Where
t : the wall thickness
k : the thermal conductivity of the wall
hi : the fermenter-side heat transfer coefficient
ho : the jacket-side heat transfer coefficient
hfi : the fermenter-side fouling coefficient
hfo : the jacket-side fouling coefficient

Heat Transfer Coefficients in coils

Heat transfer coefficient for flow inside internal
coils is estimated in the same way as flow
through a pipe.
A correction factor can be applied to account for
the effect of the curved pipe.
hi ( coil ) = hi ( straight pipe) 1 + 3.5

d
dc

Where d is the inside diameter of the tube and

d cis the diameter of the coil.

Empirical correlations for heat

transfer
h = f (v, d, other rheological properties)
where:
v = velocity (LT-1) of agitator, fluid
d = diameter (L) of agitator, flow channels
The relationship between h and v, d is not
linear!

Correlations for the Tank

Hewitt contains 12 correlations for nonproximity mixers,
covering different mixers, tank geometries and baffles.
Many correlations give geometric correction factors for
different tank geometries.
For the inside of the vessel the Reynolds number is
based on the diameter and speed of the mixer.
The Nusselt number is based on the diameter of the
tank.
Re =

NDi2

, Nu =

hDv
k

Where :
N is the rotational speed of the stirrer in rev/s.
D i is the diameter of the stirrer (propeller or turbine).

Fermenter Agitation
The agitation within the vessel can be
classified as proximity and nonproximity.
Fermenters are typically nonproximity
agitators low viscosity systems
Propeller
Turbine

Fermenter Correlations
hi = a

Di2 N

cp
k

f geom

Remember Reynolds number for inside of a tank

is based on the internal diameter of the impeller
Correlations are accurate +/- 20% for unaerated
fluids
hi for fermenters is typically 80-350W/m2K
Unfortunately the correlations are not for aerated
fermentation broths

D v is the diameter of the vessel.

Heat Transfer - Limitations

Refrigeration is expensive
Limiting cooling water temperature
Using coolants below freezing adds extra problems

Increasing jacket flowrate leads to larger

pressure drop
Limiting the coolant flowrate

Increasing Agitation
Shear limitations

Internal Coils
Cleaning

Heat Transfer - Limitations

Internal Coils
Cleaning

External Heat Exchangers

Problems with sterility
Pumping problems
aseptic
cavitation
damage to organisms

Links between OTR and Heat

Transfer
Increasing the OTR can lead to an
increase in heat generation.
At small scale increasing the OTR doesnt
cause heat transfer problems.
As the scale of the fermenter increases
satisfying high oxygen demand causes
difficulty in removing the associated heat.

Fluid types
Newtonian
water, gases, dilute solutions

Pseudoplastic
adhesives, cellulose acetate, greases

Dilatent
Corn flour and sugar solutions, starch

Bingham plastic
margarine, cooking oils

Casson plastic
blood

Viscosity of fermentation media

Viscosity can vary over the course of
fermentation
Saccharomyces cerevisiae Newtonian
below 10 % solids, pseudoplastic above
10 % solids
Aspergillus niger pseudoplastic
(filamentous)
Penicillium spp. Bingham plastic,
Casson plastic

Mixing
Reduces gradients:
concentration
temperature

Factors affecting viscosity

Cell concentration
Cell morphology
Osmotic pressure of medium
Concentrations of substrates and products
Shear rate

Kolmogorov scale of mixing or Scale

of Turbulence
Characteristic dimension of smallest
eddies is given by:
=

Increases mass transfer

increases turbulence
decreases bubble size

Maintains suspensions

where :
Characteristic dimension of smallest eddy
Kinematic viscosity
Local rate of turbulent energy of
dissipation per unit mass of
liquid

P
=
V

1/ 4

[ ] = L
[ ] = m 2s 1 = L2T 1
[] = W kg 1 = L2T 3
p146

Power requirements for mixing

Power requirements for mixing

N = f (Re )

102

d 2

P
N=
3d 5
where :

Re =
There is a correlation
between the N and
Re number (see next
slides).

[] = T 1
[d] = L

10 laminar (slow) flow

Stirrer speed

0.1

Impeller diameter
P151, Doran

Power requirements for mixing

k
where k = 10 103
Re

Turbulent flow :
N = constant = 0.1 10

Example (continued)
5

P1 N13d1
Nd
=
= 1 1
P2 N 23d 2 5 N 2 d 2 5
5

Re 2 d1
d d
d
= 22 15 = 1
5
d2
Re1 d 2
d1 d 2

1
2

1
32

10

102

103

104

105

Re

p150

Example

Example

Laminar flow :

Marine propeller

What is the effect on the power

requirement for a fermenter of doubling
the impeller diameter in laminar and
turbulent conditions?
Assume a constant impeller speed.

Laminar flow :

turbulent (fast) flow

P is the power

N=

Rushton turbine
Paddle

NP

Power number

1
8

What is the effect on the power

requirement for a fermenter of doubling
the impeller speed in laminar and turbulent
conditions?
Assume a constant impeller diameter.

Turbulent flow :
5

P1 N3d1
d
=
= 1
P2 N3d 2 5
d2

1
2

Example (continued)

Power requirements for mixing

Laminar flow :

Power requirement for mixing is highly

non-linear with respect to fluid velocity
A law of diminishing return applies:

Re 2 1

= 2 13 = 1
3
2
Re1 2
12

1
2

1
4

Turbulent flow :
3

P1 N1 d 5

=
= 1
P2 N2 3d 5
2

1
2

1
8

fluid velocity
(mixing)

P1 N11 d 5
N
=
= 1 1
P2 N 22 3d 5 N 2 2 3

power

Gas sparging
Gas sparging reduces the power
requirements for mixing, due to reduction in
density of the fluid and formation of cavities
behind impeller blades.

Scale up
What is the effect on the power-to-volume
ratio of a 100-fold scale up of a fermenter
if the same degree of mixing (or
characteristic mixing time) is required?

The relationship is not well understood.

The characteristic mixing time can be

interpreted as the time required for fluid to
traverse the characteristic dimension of
the fermenter.

Scale up

Scale up

The change in characteristic dimension of

the fermenter is calculated from the
change in volume:
V L3
V1
L
= 1
V2
L2
L1
V
= 1
L2
V2

The characteristic mixing time is the

inverse of impeller speed, . Thus the
degree of mixing is preserved if is
preserved. In turbulent flow, the mixing
number is constant:
P = N 3d 5

1/ 3

1
100

P N 3d 5
=
= N 3d 2
V
d3

1/ 3

= 0.21

P1 V1 N 3d1
d
=
= 1
P2 V2 N 3d 2 2
d2

V1
V2

2/3

1
100

2/3

= 0.05

10

Scale up
A 100-fold increase in fermenter volume
requires a 20-fold increase in P/V and,
hence, a 20 100 = 2 000 fold increase in
power!
This places economic and technical limits
on scale up

NonNon-Newtonian fluids
Viscosity is a function of shear rate (it is not
constant)
Correlations for N=f(Re) must take account
of change in viscosity with shear

Characteristic times
The characteristic time for mixing (1/
) should not
be confused with the characteristic time for mass
transfer (1/kla)
Mixing time is the time required for damping
concentration gradients while mass transfer time is
the time required for diffusion across the liquid side
boundary layer
Scale up can satisfy either constant mixing time or
constant mass transfer time

References
1. Chapter 1 of Bioprocess Engineering,
Lydersen, DElia and Nelson.
2. Bioprocess Engineering Principles, Chapter
7& 8 & 9, Pauline M. Doran 2004.

Change in P/V ratios with scale up become

much worse for shear thickening fluids but
better for shear thinning fluids

Summary
Oxygen Transfer Rate
Fundamentals
Practical Considerations

Heat Transfer
Fundamentals
Practical Considerations

Importance of Broth Rheology

Link between OTR and Heat Transfer
Design Problem

11