1

DESIGN OF FERMENTATION
PROCESSES
Chapter 9
Designing the process
What reactor?
Stirred tank reactor, airlift, plug flow reactor..
What mode of operation?
Batch, fed-batch, continuous operation
What conditions?
Substrate concentrations, residence times, pH, T..
2
stirrer
sparger
sparger
draft
tube
medium
inlet
aeration
bed with e.g.
immobilized
cells
pump
a b c d e
aeration
Reactor types
Reactor type/
Mode of operation
Advantages Disadvantages
Stirred Tank Reactors
1. Steady state(CSTR)












2. Batchoperation







3. Fed-Batch operation




Plug Flow Reactor
1. Steady state







a. Largescale productionof
cheap products STR, especially
CSTR, is by far thebest dueto
low capital and labour costs.
b. CSTR (or Fed-Batch) needed
when production of thedesired
product is cataboliterepressed.
c. Dueto autocatalytic natureof
microbial reactions, productivity
is high.
d. Product quality is constant


a. Easily switched between
different production duties with
low retrofittingcosts.
b. Can beproperlysterilized.
Small risk of infection and
mutation (short production time)


a. Sameadvantages as CSTR
(a. and b.).
b. Theproduction timeis limited
with smaller risk of mutations.


a. Very highconversion of the
substratecan beobtained.
b. Fixedbed operation
(immobilized enzymes or cells).
Filmreactors.
c. Highconversion of gas phase
substrates (loop-reactors).

a. Infectionis arisk, e.g.
caused by ashort stop of the
continuous feed sterilization
by steam.
b. Thestrain may mutateto
a non-producing strain after
longproduction time.
c. Down-streamequipment
can be difficult to operate in
thecontinuous mode.
d. Very inflexible


a. High labour costs.
b. Much idletimefor
sterilization, outgrowth of
inoculumand cleaning.
c. Safety problems when
fillingand emptyingreactor


a. Morelabour cost than
CSTR.
b. Largevolumeto bedown
streamprocessed between
runs. Holdingtanks used.

a. Requirescells in feed and
it can only beused after
another reactor.
b. Thelargedifferencein
holdingtimebetween gas and
liquid prevents theuseof a
PFR alone.

3
General mass balance equation
Inflow
Outflow
V, c
v
f
, c
f
e e f f
t
v v V
dt
V d
c c q q
c
+ + = ) (
) (
v
e
, c
e
Volumetric transfer rate
(gaseous compounds)
Volumetric production rate
Batch
(no inflow, no outflow of liquid)
) (c q
c
=
dt
d 0
) 0 ( ; x t x x
dt
dx
= = =
0
) 0 ( ; s t s x Y
dt
ds
xs
= = =
4
Batch cultivation

max
=0.5 h
-1
, K
s
=0.1 g L
-1
0 2 4 6 8 10 12 14 16 18 20
-20
0
20
40
60
80
100
Time (h)
S
u
b
s
t
r
a
t
e

&

b
i
o
m
a
s
s

c
o
n
c
e
n
t
r
a
t
o
n
s
Monod kinetics
Dimensionless time (O)
0 1 2 3 4 5 6
D
i
m
e
n
s
i
o
n
l
e
s
s

b
i
o
m
a
s
s

c
o
n
c
e
n
t
r
a
t
i
o
n
10
-3
10
-2
10
-1
10
0
10
1
D
i
m
e
n
s
i
o
n
l
e
s
s

s
u
b
s
t
r
a
t
e

c
o
n
c
e
n
t
r
a
t
i
o
n
10
-4
10
-3
10
-2
10
-1
10
0
A straight line (for all practical purposes)
5
Continuous cultivation
with constant volume
D =
Inflow
Outflow
) ( ) ( c c c q
c
+ =
f
V
v
dt
d
Dx x
K s
s
x q
s
x
=
+
= =
max

Chemostat
Substrate concentration?
D
DK
s D
s K
s
s
s

= =
+
max
max

f s
f
s K
s
D
+
s
max

Monod kinetics
Prerequisite:
If the last equation is not fulfilled, wash-out occurs
6
Chemostat

max
=0.5 h
-1
, K
s
=0.1 g L
-1
wash-out
0 0.1 0.2 0.3 0.4 0.5 0.6
0
20
40
60
80
100
120
Monod kinetics
D (1/h)
C
o
n
c
e
n
t
r
a
t
i
o
n


(
g
/
L
)
Biomass
Substrate
The equations canbe putin dimensionless
form
s K
s
s
m
+
=

S a
S
m
+
=

f
s
s
S =
f
s
s
K
a =
Since 1 0 s s S we get
1
1
+
s
a
m

7
What dilution rate gives the maximum
productivity?
x q Dx ty productivi = =
0 0.1 0.2 0.3 0.4 0.5 0.6
-10
0
10
20
30
40
50
Chemostat Monod kinetics
D (1/h)
P
r
o
d
u
c
t
i
v
i
t
y

(
g
/
L

h
)
Optimum
Optimum conditions
0
) (
=
dD
Dx d
0
) (
0
) (
max
=
|
|
.
|

\
|

+
=
ds
s s Y
s K
s
d
ds
Dx d
f SX
s

But somewhat simpler to derive is..

0 2
2
= +
f s s
s K s K s f s s s
opt
s K K K s + + =
2
0
) 1 (
max
=
|
.
|

\
|

+
dS
S
S a
S
d Y
SX

0 2
2
= + a aS S a a a S
opt
+ + =
2
Or alternatively using S and a, we get:
8
Chemostat with substrate inhibition
s K
K
s
s
s
i
m
+ +
=
2

A typical kinetic expression is

in this case
In dimensionless form
a S bS
S
m
+ +
=
2

f
s
s
K
a =
i
f
K
s
b =
where
b
a
S
opt
= It is easily shown that has a maximum for
Chemostatw substrateinhibition
1 S
/
m
1 S
/
m
Optimum for s <s
f
Optimum for s >s
f
Multiple steady-states possible
9
Fed-batch
x
dt
dV
V
x
dt
dx
dt
Vx d
x V
1 ) (
= =
Inflow
Often x
f
=0
NOTE! Volume changes
with time
x
V dt
dx
) (
v
=
Note: Chain rule
Plug flow reactor (PFR)
The PFR requires that the inflow contains biomass (or that
biomass is retained)
The PFR is therefore used primarily for immobilized
systems, but may also be used as a final reactor in a
reactor system
10
PFR- Mass balances
0 ) ( = + + dV q ds s s
S
v v
S
q
dV
ds
= v
v, s
f
dV
}

=
S
S
x
x
S
S
f
q
dx
s
V
0
v
) 1 (
S f
x s s =
The reactor volume is thus obtained from integrating 1/q
s
Capacity comparisons
The capacity of a given reactor can be said to be given
by the residence time, t, required to obtain a specified
degree of conversion of the substrate.
For a reactant, s, we obtain from mass balances:
Tank reactor Plug flow reactor
0 ) ( = + V s q s s
out s out f
v v
) (s q
s s
V
s
out f

=
v
0 ) ( ) ( = + + dV s q ds s s
s
v v
0 ) ( = + dV s q ds
s
v
}

=
f
out
s
s s
s q
ds V
) ( v
t
v
= =
D
V 1
11
For a first order reaction,
we qualitatively get
s
-q
s
s
s
q
1
s
f s
out
PFR
s
s
q
1
s
f s
out
Tank
i.e. for a first order
reaction, the PFR is to be
prefered (since the
colored area is smaller)
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
0
1
2
3
4
5
6
7
8
9
10
xs
1
/
q
s
CSTR
PFR
) 1 (
) 1 (
max
S f s
S f S f
S
x s K
x s x s
q
+

=

Monod kinetics
max
=0.5 h
-1
, K
s
=1 g/l and sf =10 g/l.
WithMonodkinetics, the picturechanges..
12
Cell recirculation
centrifuge
v, s
f
x
e
, s, p v
x
R
, s,
p
vR
v(R+1)
x, s, p
Same volumetric flow rate into and out of system
Higher flow rate after
the mixing point