Biomedical Engineering Reference
In-Depth Information
cultivation [
22
], demonstrating the transfer of the technique to another organism.
However, this method is applied to standard cell growth in 15 and 30-L reactors.
The method is not applicable after, e.g., product induction, due to the changing
heat balance while the cells change their metabolism.
Soons et al. [
23
] applied the cascade principle to precisely control the dissolved
oxygen using the oxygen in the reactor headspace (slave loop) and the dissolved
oxygen in the medium (master loop). They employ a closed-loop control based on
the DO concentration. With the simplification that the oxygen uptake rate is
proportional to the OTR, the specific growth rate of the cultivation can be held at a
constant level by controlling the DO concentration. This is shown in Eq. (
5
).
According to Fig.
3
, the closed-loop control of the dissolved oxygen is carried out
through the cascade control. The outer loop (Eq.
7
) compares the measured DO
(DO
sensor
) with the set-point. The result is handed to the inner loop (Eq.
8
), cal-
culating the controller output through the difference between headspace and
medium.
OUR
¼
OTR
¼
k
L
a O
2
;
head
DO
ð
5
Þ
OTR
dO
2
;
head
dt
¼
F
0
2
V
head
O
2
;
in
O
2
;
head
ð
6
Þ
þ
K
i
Z
t
0
ds
O
2
;
a
¼
K
p
DO
set
DO
ðÞ
sensor
DO
set
DO
ðÞ
sensor
ð
7
Þ
þ
K
i
Z
t
0
ds
O
2
;
in
¼
K
p
O
ðÞ
2
;
a
O
ðÞ
2
;
head
O
ðÞ
2
;
a
O
ðÞ
2
;
head
ð
8
Þ
The cascade is realized by using the result of the PI control action of Eq. (
7
)in
the control action of Eq. (
8
). This provides more flexible and sophisticated control
compared with if only one PI controller were to be employed, because not only the
transport of oxygen between the gas flow and the medium is considered, but also
the transport from the headspace of the reactor into the medium. Further, Soons
et al. use a Kalman filter to calculate the specific growth rate from the oxygen
consumption provided from the DO control cascade. They demonstrated the
implementation of a stable and robust closed-loop controller for specific growth
rate control. The method does not need an online model and therefore lacks a
complex implementation. They show through simulations and fed-batch experi-
ments that the controller is robust against disturbances and able to maintain the
specific growth rate of vaccine-producing Bordetella pertussis at a constant level
of l = 0.05 h
-1
.
Bodizs et al. [
24
] observed that a simple PI controller for DO does not perform
well enough in their system and therefore employed a cascade controller. Since
they implemented the controller for an established reactor, they used a set of
available multiple inputs, namely OUR, CPR, DO, and volume. The process is a
2,700-L fed-batch filamentous fungal fermentation. The control is applied to
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