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CEN 551
Instructor: Dr. Christine Kelly
Chapter 9
Bioreactors
Productivity
Flexibility
Control
Genetic stability
Operability
Economics
Regulatory
What do each
of these factors
mean?
Reactor Choices
Y
X/ S
S
0
1
max
ln
X
max
X
0
+ t
l
Recall the definition of biomass yield: Recall the definition of biomass yield:
Y
X/ S
X
S
X
max
X
0
S
0
0
X
max
X
0
S
0
Pr
X
batch
X
max
X
0
t
cycle
(1) (1)
Chemostat
For negligible k
d
, negligible extracellular product
formation and steady state, Lec. Notes 16, Eq. (10)
gave:
For negligible k
d
, negligible extracellular product
formation and steady state, Lec. Notes 16, Eq. (10)
gave:
X Y
X/ S
S
0
K
S
D
max
D
_
,
For optimum cell productivity (XD), calculate
d(XD)/dt, set equal to zero, and solve for D
opt
:
For optimum cell productivity (XD), calculate
d(XD)/dt, set equal to zero, and solve for D
opt
:
D
opt
max
1
K
S
K
S
+ S
0
_
,
(3) (3)
(2) (2)
Chemostat
Substituting Eq. (2) into Eq. (3) gives the value
of X at the maximum production rate. :
Substituting Eq. (2) into Eq. (3) gives the value
of X at the maximum production rate. :
( ) [ ]
S 0 S S 0 X/S opt
K S K K S Y ) D (at X + +
Optimum productivity is DX when D=D
opt
and X= X
(at D
opt
):
Optimum productivity is DX when D=D
opt
and X= X
(at D
opt
):
( ) ( ) [ ]
S 0 S S 0
0 S
S
max X/S
chemo opt,
X
K S K K S
S K
K
1 Y Pr + +
1
]
1
+
(4) (4)
(5) (5)
Chemostat Productivity Rate
Noting that S
0
is usually much larger than K
S
, we
have:
Noting that S
0
is usually much larger than K
S
, we
have:
Pr
X
opt, chemo
max
Y
X/ S
S
0
Comparing the rates for batch production and
production in a chemostat:
Comparing the rates for batch production and
production in a chemostat:
Pr
x
opt , chemo
Pr
x
batch
ln
X
max
X
0
max
t
l
(6) (6)
(7) (7)
Comparison
X
max
is always larger than X
0
and is typically 10-20
times larger, so the chemostat outperforms the
batch reactor. For E. coli growing on glucose,
max
is around 1/hr. Using t
lag
=5 hr and X
max
/X
0
=20,
X
max
is always larger than X
0
and is typically 10-20
times larger, so the chemostat outperforms the
batch reactor. For E. coli growing on glucose,
max
is around 1/hr. Using t
lag
=5 hr and X
max
/X
0
=20,
Pr
x
opt , chemo
Pr
x
batch
8
Even so, most industrial fermentation processes
occur in a batch reactor. Why?
Even so, most industrial fermentation processes
occur in a batch reactor. Why?
Reasons for Batch Popularity
Multistage chemostat
Fed-batch
Perfusion
Chemostat with Recycle
Can we operate a chemostat with a dilution
rate greater than maximum growth rate?
Why or why not?
What conditions would we want to operate
a chemostat with a dilution rate higher
than the maximum growth rate?
High dilution rate
No
max
<D. Higher dilution rates can be
achieved with recycle.
F
S
0
X
0
F
S
0
X
0
(1+)F
S,X
(1+)F
S,X
F
S,X
F
S,X
F
X
F
X
Chemostat with Recycle
Biomass balance on the chemostat:
( ) VX FX 1 FX FX
dt
dX
V
0
+ + +
where =volumetric recycle ratio and =the
concentration factor of the separator. At steady
state and with X
0
=0:
where =volumetric recycle ratio and =the
concentration factor of the separator. At steady
state and with X
0
=0:
( ) 0 X X
V
F
1 X
V
F
+ +
( ) [ ]D 1 1 +
Note that for >1, <D. Note that for >1, <D.
(8) (8)
(9) (9)
(10) (10)
Substrate Mass Balance
V
dS
dt
FS
0
+ FS V
X
Y
X/ S
1 + ( )FS
F
V
S
0
+
F
V
S
X
Y
X/ S
1 + ( )
F
V
S 0
X
D
Y
X/ S
S
0
S
At steady state: At steady state:
(11) (11)
(12) (12)
(13) (13)
Steady-state Values
Substituting given by Eq. (10) into Eq. (13): Substituting given by Eq. (10) into Eq. (13):
X
Y
X/ S
S
0
S
1 1
(14) (14)
We can get the expression for the substrate
concentration by equating the expression for
from Monod kinetics to Eq. (10):
We can get the expression for the substrate
concentration by equating the expression for
from Monod kinetics to Eq. (10):
Steady-state Values
max
S
K
S
+ S
1 + 1 D
or: or:
S
K
S
D 1 + 1
max
D 1 + 1
(16) (16)
(15) (15)
So now we can get X entirely as a function of D: So now we can get X entirely as a function of D:
X
Y
X/ S
1 + 1
S
0
K
S
D 1 + 1
max
D 1 + 1
1
]
1
(17) (17)
Special Cases - Chemostat
Notation:
S
0
= initial substrate concentration of batch
V
0
= initial volume of batch
F= constant flow rate of addition stream during fed-batch
X
0
= initial concentration of batch
S
0
= initial substrate concentration of batch
V
0
= initial volume of batch
F= constant flow rate of addition stream during fed-batch
X
0
= initial concentration of batch
Since liquid is being added, the volume
is changing:
Since liquid is being added, the volume
is changing:
dV
dt
F
V V
0
+ Ft
X X
0
+Y
X/ S
S
0
S ( )
For a batch culture: For a batch culture:
or: or:
If the total amount of biomass (grams)
in the reactor is X
t
then the
concentration X is:
If the total amount of biomass (grams)
in the reactor is X
t
then the
concentration X is:
X X
t
/ V
(1) (1)
(2) (2)
(3) (3)
So the change in the biomass
concentration with time is:
So the change in the biomass
concentration with time is:
dX
dt
V
dX
t
dt
_
,
X
t
dV
dt
_
,
V
2
Using the definition of the growth rate: Using the definition of the growth rate:
...the dilution rate: ...the dilution rate:
...and the expression for dV/dt: ...and the expression for dV/dt:
1
X
t
dX
t
dt
D
F
V
dV
dt
F
we have: we have:
dX
dt
D ( )X
(4) (4)
(5) (5)
Now, consider the case when the fed-
batch is started from a culture in the
initial substrate concentration was S
0
and
nutrient feed is begun at flow rate F and
concentration S
0
. Just as nutrient feed
begins:
Now, consider the case when the fed-
batch is started from a culture in the
initial substrate concentration was S
0
and
nutrient feed is begun at flow rate F and
concentration S
0
. Just as nutrient feed
begins:
Quasi-steady State
max
D
(7) (7)
(8) (8)
(9) (9)
If the total amount of substrate in the reactor
is S
t
, then a substrate mass balance gives:
If the total amount of substrate in the reactor
is S
t
, then a substrate mass balance gives:
dS
t
dt
FS
0
X
t
Y
X/ S
which, for quasi-steady state gives: which, for quasi-steady state gives:
FS
0
X
t
Y
X/ S
Returning to Equation (4), we have, at
quasi-steady state:
Returning to Equation (4), we have, at
quasi-steady state:
dX
t
dt
X
t
V
dV
dt
_
,
XF
(10) (10)
(11) (11)
(12) (12)
Integrating, we have: Integrating, we have:
X
t
X
0
t
+ FXt
since X is constant (dX/dt=0). Therefore, the
total biomass in a fed-batch reactor operated as
assumed here increases linearly with time.
Substituting the appropriate expression for X:
since X is constant (dX/dt=0). Therefore, the
total biomass in a fed-batch reactor operated as
assumed here increases linearly with time.
Substituting the appropriate expression for X:
( ) [ ] t S S Y X F X X
0 X/S 0
t
0
t
+ +
Often, S<<S
0
and X
0
<<Y
X/S
S
0
and so: Often, S<<S
0
and X
0
<<Y
X/S
S
0
and so:
X
t
X
0
t
+ FY
X/ S
S
o
t
(13) (13)
(14) (14)
(15) (15)
If the specific productivity (g product/g cells/
hr) is constant:
If the specific productivity (g product/g cells/
hr) is constant:
Product Output
1
X
t
dP
t
dt
q
p
dP
t
dt
q
p
X
t
where P
t
is the total product concentration in the
reactor:
where P
t
is the total product concentration in the
reactor:
or: or:
Substituting: Substituting:
X
t
VX V
0
+ Ft X
(16) (16)
we have: we have:
dP
t
dt
q
p
X V
0
Ft
Integrating this expression, we
have:
Integrating this expression, we
have:
P
t
P
0
t
+ q
p
X V
0
+
Ft
2
_
,
t
or in terms of concentration: or in terms of concentration:
P P
0
V
0
V
+ q
p
X
V
0
V
+
Dt
2
_
,
t
(17) (17)
(18) (18)
(19) (19)
Repeated Fed-batch
Usually, fed-batch cultures are taken
through many feeding cycles, with
each feeding cycle followed by a
harvest cycle during which the
volume is drawn back down to V
0
and the cycle begun again.
For the case of repeated fed-batch
cultures:
For the case of repeated fed-batch
cultures:
P
w
P
0
+ q
p
X +
D
w
t
w
2
_
,
t
w
Where V
w
is the volume just before harvesting,
V
0
is the volume after harvesting, D
w
=F/V
w
and:
Where V
w
is the volume just before harvesting,
V
0
is the volume after harvesting, D
w
=F/V
w
and:
V
0
V
w
t
w
is the cycle time and is given by: t
w
is the cycle time and is given by:
t
w
V
w
V
0
F
V
w
V
w
F
1
D
w
(20) (20)
(21) (21)
(22) (22)
With this definition, we now
have:
With this definition, we now
have:
( )
2
w
p
0 w
1
2D
X q
P P +
(23) (23)
Perfusion Culture
Cell retention
Cell reuse
Genetic stability
Damkohler number
Effectiveness factor
Thiele modulus
Immobilized Bioreactors
Energy efficiency