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# Institution of Chemical Engineers
www.ingentaselect.com=titles=09603085.htm Trans IChemE, Vol 81, Part C, December 2003

GENERALIZED MINIMUM VARIANCE CONTROL OF

GROWTH MEDIUM TEMPERATURE OF BAKERÂS
YEAST PRODUCTION
S. ERTUNÇ1 , B. AKAY1 , N. BURSALI2 , H. HAPOG LU1 and M. ALPBAZ1
1
Ankara University, Faculty of Engineering, Department of Chemical Engineering, Tandog
 an, Ankara, Turkey
2
Yenimahalle Municipality, Department of Health, Yenimahalle, Ankara, Turkey

T
he control of optimum growth medium temperature of a batch bioreactor in which
S.cerevisiae was grown under aerobic conditions has been studied. The generalized
minimum variance (GMV) algorithm was applied for on-line computer control. A
controlled autoregressive moving average model relating the bioreactor temperature and heat
input was used to show the dynamic behaviour of the system. The heat input to the bioreactor
was chosen as a manipulated variable. A pseudo-random binary sequence signal was applied to
the system and the model parameters were determined using the Bierman algorithm. More
suitable values of the GMV controller parameters were determined using a total simulation
program. These control parameters were used in experimental and theoretical work under
several disturbances.

Keywords: bioreactor; parameter estimation; modelling; generalized minimum variance.

INTRODUCTION by minimizing a cost function for a provided linear input–

In process operation, whether chemical or biochemical, the
production of high-quality product, maximum proŽ t and
safe operation are desired. All of these purposes generally
require control of the operation parameters. However,
bioprocesses require extra control because of the number
of complex reactions which take place simultaneously and
which cannot be deŽ ned with simple mathematical models;
in addition, there are no suitable state sensors.
In recent years, there has been a great deal of interest in
the application of bioprocesses in food, agriculture and
pharmaceutical industries and the solution of the problems
in these processes. As a result, modern control techniques
have been developed to control the growth medium tempera-
ture, pH, gas  ow rate and substrate feed rate (Sargantanis
et al., 1998; Dochain and Bastin, 1984).
Saccharomyces cerevisiae, known as Baker’s yeast, was
used and the production of this microorganism in the batch
culture was desired. Until now in the production of Baker’s
yeast, whether continuous, batch or fed-batch bioreactors,
different operating parameters have been controlled using
modern control techniques so that maximum yeast produc-
tion and economical proŽ t can be achieved. One of the most
popular control techniques is the self-tuning method. Genera-
lized minimum variance, pole-placement self-tuning and
generalized predictive control are known as self-tuning
control techniques.
The generalized minimum variance (GMV) controller
(Clarke and Gawhrop, 1975) was formed basically as a
modiŽ cation of the minimum variance (MV) technique of
Aström and Wittenmark (1973). This controller is obtained
output model. It is well known that MV controllers (Aström
et al., 1977) attempt to cancel explicitly the forward path
zeros, some of which may lie outside the unit circle. In MV
control it is critical that the time delay should be correctly
chosen (Hang et al., 1991). Wrong values of time delay can
destabilize the control or at least result in deviations of the
controlled variable. The GMV algorithm involves a feed-
forward element represented by the polynomial Q. The
presence of this usually avoids the problems which destabi-
lize the system. The GMV control law (Clarke and
Gawhrop, 1975) employs a one-step-ahead optimal control
strategy. The evaluated parameters are employed precisely in
the implicit GMV algorithm. However, due to the implicit
character of this algorithm it can be shown that the design
parameters of the controller cannot be varied on-line without
degrading the parameter estimates (Clarke and Gawhrop,
1975). An additional modiŽ cation to this design (Clarke and
Gawtthrop, 1979) permits the control weighting to be altered
on-line without in uencing the parameter estimates. In the
latter case, the control law is not completely implicit (Pamuk
et al., 2000).
The purpose of this study is to control the culture medium
temperature at which the concentration of the microorgan-
ism can be held at a maximum. In the Ž rst part of the work, a
mathematical model of the bioreactor was developed to
observe and calculate the transient behaviour of the
system and then a CARMA model was used to achieve
the GMV control. The related model was solved by digital
computer and was used in a total simulation program.
In the second part of the work, some theoretical work was
realized to obtain the temperature control and to track the

327
328 ERTUNÇ et al.

bioreactor temperature. Heat input was chosen as a manipu- Yeast growth rate for exponential growth phase is given by
lated variable. A total simulation program was used to
dX
obtain the related CARMA model and control parameters. ˆ mX (3)
Firstly CARMA model parameters were determined by dt
using the Bierman algorithm (Biermann, 1976) and then A functional relationship between the speciŽ c growth rate
using these parameters a CARMA model was applied to (m) and an essential compound’s concentration was proposed
achieve sufŽ cient GMV control performance. Secondly by Monod (Clarke and Gawtthrop, 1979).
some control parameters were tested theoretically to deter-
mmax S
mine the best values of them; using these parameters the mˆ (4)
GMV control system was examined theoretically. In the KS ‡ S
third part of the work, the calculated optimal control and The Monod equation in its original form is not well suited
model parameters were used to realize GMV control experi- for estimation of the parameters mmax and KS. Therefore, by
mentally. Very satisfactory control results were achieved. rearranging equation (4) the following options can be
derived for data plotting and graphical parameter evaluation:
MATHEMATICAL MODEL OF THE BIOREACTOR 1 K 1 1
ˆ S ‡ (5)
In this study the following stoichiometric illustrations m mmax S mmax
were considered to occur in the batch culture. plotting equation (5) as 1=m vs 1=S is known as Lineweaver–
Burke plot.
(1) Yeast growth:
The stationary phase starts at the end of exponential phase
aC6 H12O6 ‡ bO2 ‡ c(NH4 )2 SO4 dX
ˆ0 (6)
! d(cells) ‡ eH2 O ‡ f CO2 ‡ DHC dt
The death phase follows the stationary phase and the rate of
(2) Glucose catabolism via oxidative pathway: death is described with Ž rst-order kinetics:
dX
C6 H12 O6 ‡ 6O2 ! 6CO2 ‡ 6H2 O ˆ ¡kd X (7)
dt
¡1
¡DHS ˆ 673 kcal mol substrate The parameters of these kinetic models were deŽ ned by
means of the related experimental curve and a computer data
Some assumptions were made in the mathematical model- bank. A plot of ln X vs t yields a line of slope ¡kd (Shuler
ling of the cooling jacketed batch bioreactor. These are: and Kargi, 1992). The least square method was used to
° the bioreactor was assumed to be a well-mixed one with calculate the kinetic parameters.
The rate of oxygen uptake is denoted as OUR (oxygen
temperature and cell concentration not varying with
uptake rate):
position in the bioreactor;
° the mean speciŽ c heat capacity of the system contents is mX
OUR ˆ (8)
independent of the composition and temperature changes; Y X= O2
° the inlet temperature of the cooling water was assumed to DX
be constant; YX=O2 ˆ ¡ (9)
DO2
° the decrease in volume due to increase in density was
neglected, therefore the changes of biomass concentration The global dissolved oxygen material balance in the growth
were accepted as being equal to changes occurring during medium in the presence of oxygen-consuming cells is
written as follows (Cardello and San, 1988):
the exponential growing phase;
° it was assumed that the change of viscosity had no effect d(DO) mX
ˆ kL a[(He1 CO ) ¡ DO] ¡ (10)
upon the reaction kinetics; dt YX = O 2
° the speciŽ c heat of the vessel is relatively smaller than
Exit oxygen material balance in gas phase is:
that of the reaction mixture; it is therefore omitted and µ
does not affect any discrepancies between the model and dCO RT
the experimental results. ˆ i ¡ kL a[(He1 CO ) ¡ DO]
dt epM1
¶
Material balances on yeast growth under aerobic condi- P M F(Yin ¡ CO )
tions are given below. ‡ i 1 (11)
RTVL
Model for glucose consumption
Yield factor based on CO2 is:
dS mX
ˆ¡ (1) DX
dt YX=S YX=CO2 ˆ (12)
DCO2
where YX=S yield factor is given by: Dissolved CO2 material balance in growth medium:
DX d(DCO2 ) mX
YX=S ˆ ¡ (2) ˆ ¡ (KL a)c (DCO 2 ¡ He2 CCO2 ) (13)
DS dt YX=CO2

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 GENERALIZED MINIMUM VARIANCE CONTROL 329

Table 1. Values of the kinetic parameters

Exit CO2 material balance in gas phase:
µ (Biermann, 1976).
dCCO2 RT
ˆ i (kL a)c (DCO2 ¡ He2 CCO2 ) Parameter Value
dt epM2
¶ He1 0.03488g O2 l¡1
Pi M2 FCCO2 e 0.15
‡ (14) 4.4 kcal g cell¡1
RTVL DHc
DHs 673 kcal mol substrate¡1
The total rate of heat evolution in the bioreactor depends on YX=S 0.33 g cell g O2¡1
the heat balance and can be illustrated as a schematic Yin 0.21
YX=O2 1.3 g cell g O2¡1
representation of energy balance for microbial utilization KS 2.14 g l¡1
of substrate (see Figure 1). r 0.984 g cm¡3
The heat of combustion of the substrate is equal to the CP 0.987cal g¡1 ¯ C¡1
sum of metabolic heat (1=YH) and the heat of combustion of
the cellular material (DHC ).
DHs 1 GENERALIZED MINIMUM VARIANCE CONTROL
ˆ DHc ‡ (15)
YX=S YH
The minimum variance (MV) controller is attained by
Equation (15) can be rearranged to yield minimizing, for a provided linear input–output model, the
Y X= S tracking criterion,
YH ˆ (16)
DHs ¡ (YX=S DHc )
J (u, t) ˆ E{( yt‡k ¡ rt‡k )2 } (21)
DHs and DHc can be determined from the combustion of
substrate and microbial cell (Shuler and Kargi, 1992). For where E is the expectation and k is the supposed delay.
cells growing actively, generated reaction heat (QGR) is This criterion is minimized at time t by the choice of a
proportional to the growing rate. The generated reaction suitable control signal ut. At time t ‡ Dt a new state exists
heat can be calculated from the heat of combustion of the which will result in a new value of u. If the supposed delay
substrate and cellular material. All the kinetic parameters are is less than the real system delay, then the control signal will
given in Table 1. try to remove output noise elements before the signal can be
1 transmitted through the system delay. The consequence is an
QGR ˆ VL mX (17) unrealizable controller which can produce large feedback
YH gains which Ž nally destabilize the system. On the other
Energy balance for the jacketted bioreactor is: hand, if the supposed delay is larger than the system delay,
then the noise will not be decreased to its lowest attainable
dT 1
VL rCP ˆ qih ‡ VL mX ¡ UAT (T ¡ Tc ) (18) value since the fastest transfer rate through the system is not
dt YH being employed.
T ci ‡ T co The GMV algorithm avoids the problems of removing
Tc ˆ (19) output noise before the signal transmission by using a feed-
2
forward polynomial Q. If the supposed delay is applied
Energy balance for the cooling jacket is:
within the generalized system then the feed-forward path
dTco gives the required route by which the control signal can
Vc rc CPc ˆ mc CPc (Tci ¡ Tco ) ‡ UAT (T ¡ Tc ) (20) suitably compensate the generalized output f(t) (Figure 2).
dt
The GMV cost function provides additional penalties in
All the models were used to calculate the system perfor-
terms of the process output error and the control signal, viz.,
mance of GMV control and to see the transient behaviour of
the system. A total simulation program was also used to ft‡k ˆ Pyt‡k ‡ Qut ¡ Rrt (22)
calculate the parameters of system, CARMA type model
and control parameters. where r(t) is the set point, and P, Q and R are transfer
functions in the backward shift operator z¡1, speciŽ ed as

J ˆ E{f2t‡k } (23)
P ˆ 1, Q ˆ l, Rˆ1

where l is control weighting and it is used as a control

tuning parameter. The function of the feed-forward term is
to change the system open loop zeros from B to PB ‡ QA.
This can be seen by substituting the system equation (24) in
equation (22):

C B
yt‡k ˆ e ‡ u (24)
A t‡k A t‡k
PB ‡ QA PC
ft‡k ˆ ut ‡ e ¡ Rrt (25)
Figure 1. Heat balance on microbial utilization of substrate. A A t‡k

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330 ERTUNÇ et al.

Figure 2. Diagrammatic representation of a pseudo-system.

This expression for ft‡k is effectively the addition of two MgSO4 ¢ 7H2O, 0.0017% CaCl2 ¢ 4H2O and 2% agar. The
independent terms. The Ž rst term can be deŽ ned as: cells growing on the newly prepared slants were inoculated
1 into the same liquid medium (without agar) and cultivated at
ft‡k jt ˆ [(BE ‡ QC)ut ‡ Gyt ¡ CRrt ‡ Ed] (26) 32¯ C for 24 h. Cells in the exponential growth phase were
C inoculated from the seed culture into the growth medium
and represents the best forecast of ft‡k established on data which contained 2% glucose, 0.6% yeast extract, 0.3%
up to time t. The second term is: K2HPO4, 0.335% (NH4)2SO4, 0.376% NaH2PO4, 0.052%
MgSO4 ¢ 7H2O, 0.0017% CaCl2 ¢ 4H2O and 0.2 ml antifoam A.
Eet‡k ˆ ft‡k ‡ f^ t‡k jt (27) Inoculum, 1:10, was used for the experiments. Glucose,
which is the output prediction error originating from the which was used as a carbon and energy source, and salt
noise sources et‡1 , et‡2 , . . . , et‡k . It was pointed out pre- solutions were separately sterilized in an autoclave for
viously that these latter sources cannot be removed by the 20 min at 121¯ C. The bioreactor and other ancillary equip-
control signal ut. ment were sterilized with 70% ethanol at pH 2. Air was
Clearly J is minimized by setting the predicted output supplied continuously to the bioreactor by a sparger after
equal to zero, i.e. passing it through an air rotometer and microbiological
Ž lter. Experiments were carried out at 600 rpm agitation
ft‡kjt ˆ 0 (28) rate. Cell concentration was determined turbidimetrically at
This gives the control law: 580 nm with a Shimadzu (Tokyo, Japan) model UV-160A
spectrophotometer. At every sampling time the temperature
Fut ‡ Gyt ¡ Hr t ‡ Ed ˆ 0 (29) of the growth medium was measured by a thermocouple.
where The value of the manipulated variable, which is the heat
given from the immersed heater, was computed according
F ˆ BE ‡ QC, H ˆ CR (30) to the controller algorithm settled on on-line computer
Hence: and adjusted by a triac module. A schematic of the on-line
control system and experimental system is given in Figure 3.
Hrt ¡ Gyt ¡ Ed
ut ˆ (31)
F
The steps in the implementation of the GMV algorithm may
be summarized as: RESULTS AND DISCUSSION

(1) Apply a PRBS to the system as a forcing function and
obtain the plant output.
(2) Estimate F, G, H from equation (29), implementing the
Bierman U–D update algorithm.
(3) Employ equation (31) to evaluate the control signal.
(4) Apply the control signal.
(5) Return to step (1).
EXPERIMENTAL SYSTEM
The yeast S. cerevisiae NRRL Y-567, which was obtained
from the ARS culture collection (Northern Regional
Research Center, Peoira, IL, USA), was used in the present
study. The stock cultures were maintained on agar slants
containing 2% glucose, 0.6% yeast extract, 0.3% K2HPO4,
0.335% (NH4)2SO4, 0.376% NaH2PO4, 0.052%
The application of a GMV control system to the growth
medium temperature of the bioreactor in which S. cerevisiae
was grown in aerobic conditions was realized. Theoretical
and experimental control studies were carried out to observe
the efŽ ciency of the control system.
The following experimental procedure was performed to
determine the effectiveness of the GMV control system and
to calculate the control and system model parameters.
For this purpose, growth medium was Ž lled into the jacketed
bioreactor. When the bioreactor was heated by means of an
immersed heater, cooling water was passed throughout the
reactor cooling jacket. In this case, the bioreactor can be
considered as a heat exchanger. Thus the heat given out by
the heater was absorbed by the cooling water. If this is taken
into consideration the bioreactor can be considered to be
continuous as regards energy. When such a bioreactor is
used with deŽ ned values of heat input and cooling  ow rate,

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 GENERALIZED MINIMUM VARIANCE CONTROL 331

Figure 3. Experimental system.

the system can reach the steady-state condition shown in
Table 1. In all the identiŽ cation work, this steady-state
operating condition was utilized. The mathematical model
equations of this reactor [equations (18)–(20)] were solved
using the fourth-order Runge–Kutta integration method.
This simulation algorithm with initial steady-state condition
shown in Table 1 was used to calculate the system CARMA
model and control parameters. The design philosophy of
the GMV control system basically depends on this approxi-
mation. In addition, the heat released during the reaction
was accepted as a disturbance for this system. For control
application, heat input from the immersed heater was chosen
as a manipulated variable.
Optimal operating conditions were calculated by identify-
ing a static model for S. cerevisiae production under aerobic
conditions. A two-level factorial experimental design was
used to identify a related model. Box–Wilson’s steepest-
ascent method was applied to Ž nd the optimal operating
conditions using an identiŽ ed statistical model (Box and
Wilson, 1951). Four independent variables which have an
effect on aerobic yeast production were selected. Tempera-
ture, pH, air  ow rate and agitation rate were the indepen-
dent variables. Yeast productivity was selected as the
dependent variable. A Ž rst-order statistical model was
chosen to illustrate the dependence of the yeast productivity
on the operating parameters. Optimum pH, temperature, air
 ow rate and agitation rate were determined as 5, 32¯ C,
1 vvm and 600 rpm, respectively (Alpbaz et al., 1997). All
the optimal operating conditions are shown in Table 2.
Theoretical desired and uncontrolled experimental yeast

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332 ERTUNÇ et al.

Table 2. Steady-state and optimal operating condition for the bioreactor.

control parameters. For this purpose several calculations
Two-level factorial Optimal and were performed to Ž nd the most suitable control para-
experimental steady-state meters, which were time delay and control weighting, l.
design operating The selection criteria for the values of control parameters
Parameter condition condition (l) was based on less oscillation and reaching the set point
Cooling water input 20¯ C 20¯ C in minimum time. After several trials, time delay and
temperature control weighting were found to be 0.5 min and 0.001 by
Cooling water  ow rate 46 ml min¡1 31.5 ml min¡1 observing GMV control performance to track the reactor
Steady-state heat value 60 W 60 W
Steady-state bioreactor 27–32¯ C 32¯ C temperature. These control parameters were used in the rest
temperature of the control work. The effect of the l values on the
Air  ow rate 0.5–1 vol vol¡1per min 1 vol vol¡1per min control system performance as a speciŽ c example is given
Agitation rate 300–600 rpm 600 rpm in Figure 5. The experimental and theoretical GMV control
Operating volume 1600 ml 1600 ml
Reaction time 8h 8h
system was achieved as follows.
pH 3–5 5 When the bioreactor, containing only the growth medium,
was at the optimal steady-state condition with deŽ nite values
of heating and cooling  ow rates, the reaction was started
by introducing the microorganism seed culture into the
bioreactor. Related control and uncontrolled temperature
concentration proŽ les carried out under optimum conditions
proŽ les obtained from experimental studies are shown in
are given in Figure 4. Temperature control is very effective
Figure 6. The agreement between the theoretical and experi-
to keep the yeast concentration at the desired value. Very
mental control results was satisfactory. The temperature in
little  uctuation at the desired temperature value results in a
the no-control case increased up to 34¯ C. In control cases
big difference in the yeast concentration. This can be seen
the temperature remained at ¹32¯ C. In the experimental
clearly in Figure 4.
control case, the result was more osillatory than in the
The application of GMV control system was realized to
theoretical case because of the existence of unmodelled
keep the bioreactor temperature at optimal value. The
CARMA model based on the relation between the bioreactor
temperature and heat input to the bioreactor was used. The
parameters of the CARMA model were calculated using a
simulation program having energy balances with an initial
steady-state condition. When the reactor Ž lled with the growth
media, in the steady-state condition, a PRBS signal was given
to disturb the system around the steady-state condition. From
the time response of the bioreactor temperature, the identiŽ ed
CARMA model of the bioreactor is given below:

yt ˆ 0:015ut¡1 ¡ 0:008ut¡2 ¡ 0:005ut¡3

¡ 0:501yt¡1 ¡ 0:487yt¡2 (32)

For all GMV control work, this identiŽ ed CARMA

model was used. A GMV control system based on this
model was applied to keep the reactor temperature at the
optimal value. A total simulation program having mass and
energy balance equations (10)–(21) was used to design the Figure 5. The effect of the l values on the GMV control performance.

Figure 4. Desired theoretical and experimental uncontrolled yeast concen- Figure 6. Theoretical and experimental results for the bioreactor tempera-
tration proŽ les carried out under optimum conditions. ture when GMV control is applied (l ˆ 0.000135).

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 GENERALIZED MINIMUM VARIANCE CONTROL 333

Figure 7. Yeast concentration proŽ le for GMV control. Figure 9. Yeast concentration proŽ le for GMV control under a positive step
change given to the cooling  ow rate at time 0 minute (m1 ˆ 46 ml=min,
m2 ˆ 60 ml=min).

disturbances. In addition, the time variation of the manipu-

lated variable is given in the same Ž gure. The bioreactor
temperature follows the set point without oscillation and
offset is not observed. The time variation of yeast concen-
tration is given in Figure 7. The desired product concentra-
tion is obtained with the GMV control system.
Other experimental and theoretical studies have been
carried out for additional disturbance and reaction heat
rejection. For this purpose, positive and negative step
changes were given to the cooling  ow rate. When the
bioreaction was taking place in the reactor at the beginning
of the reaction, a step change was suddenly given to the
cooling  ow rate. With this effect, the bioreactor tempera-
ture changed with time very quickly and then the GMV Figure 10. Theoretical and experimental results for the bioreactor tempera-
control system tried to tract the bioreactor temperature at ture using GMV control under a negative step change given to the cooling
the optimal value. A typical result for a positive step  ow rate at time 0 minute (m1 ˆ 46 ml=min, m2 ˆ 31.5 ml=min).
change given at 0 min is shown in Figure 8. The time
variation of yeast concentration is also given in Figure 9.
In this condition, the theoretical and experimental GMV
control system was very successful in keeping the bio- ing  ow rate. Time variation of the bioreactor temperature
reactor temperature at the desired set point. Then the Ž nal is given in Figure 10. Yeast concentration is shown in
yeast concentration was very close to the optimal desired Figure 11. Some theoretical and experimental results were
value. A similar control work was repeated for a negative obtained.
step change is introduced at 0 min given to the cool-

Figure 8. Theoretical and experimental results for the bioreactor tempera- Figure 11. Yeast concentration proŽ le for GMV control work under a
ture using GMV control under a positive step change given to the cooling negative step change given to the cooling  ow rate at time 0 minute
 ow rate at time 0 minute (m1 ˆ 46 ml=min, m2 ˆ 60 ml=min). (m1 ˆ 46 ml=min, m2 ˆ 31.5 ml=min).

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334 ERTUNÇ et al.

CONCLUSION t time, h
T bioreactor operating temperature, ¯ C
In all control work, the identiŽ cation method used in this Tc mean temperature of cooling water, ¯ C
research is very successful and applicable to design the Tci inlet temperature of cooling water, ¯ C
Tco outlet temperature of cooling water, ¯ C
GMV control system. GMV control system based on the U overall heat transfer coefŽ cient, J m¡2 s¡1 ¯ C¡1
standard CARMA model is very successful in forcing u(t), ut input variable at time t
the bioreactor temperature to follow the optimum set point Vc volume of cooling water, cm3
with little oscillation and without offset. VL volume of growth medium, cm3
In all the control work, the desired conversion was Yin inlet air oxygen mole fraction
y(t), yt output variable at time t
obtained satisfactorily. The desired yeast concentration X microorganism (yeast) concentration, g cell l¡1
was shown in Figure 4. Very small deviations from optimal YX=S substrate yield coefŽ cient, g cell g substrate¡1
set point of 32¯ C during temperature control cause consider- YX=O2 oxygen yield coefŽ cient, g cell g O2¡1
able difference in the desired yeast concentration. In the 1=YH metabolic heat evolved per gram of cell mass produced,
J g cell¡1
previously published work (Karagoz et al., 2000), the same z, z¡1 forward and backward shift operators
control strategy was applied to a polystyrene polymerization
reactor to keep the reactor temperature on a predetermined Greek symbols
trajectory. It can be seen that this control strategy is e fraction of the reactor that is occupied by a gas phase
applicable to various batch processes with different orders m speciŽ c growth rate, h¡1
and dead-times. mmax maximum growth rate, h¡1
r growth medium density, g cm¡3
Various control strategies were applied to the same rc cooling water density, g cm¡3
bioreactor for growth medium temperature of baker’s yeast DHs heat of combustion of the substrate, j mol substrate¡1
production in previously published work (Bursali et al., DHc heat of combustion of cells, j g cell¡1
2001; Akay et al., 2002; Bursali et al., 2001). The speciŽ c l control weighting
growth rate m (h¡1) was found to be 0.57, 0.5, 0.23 for ft‡kjt best forecast of f t‡k established on data up to time t
ft‡k pseudo-output
nonlinear adaptive PID control, linear adaptive PID control
and uncontrolled cases, respectively. In the present work, the
highest speciŽ c growth rate was obtained as 0.74 for GMV REFERENCES
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 GENERALIZED MINIMUM VARIANCE CONTROL 335

Shuler, M.L. and Kargi, F., 1992, Bioprocess Engineering Basic Concepts ADDRESS
(Prentice Hall, Englewood Cliffs, NJ).
Correspondence concerning this paper should be addressed to Professor
M. Alpbaz, Ankara University, Faculty of Engineering, Department of
Chemical Engineering, Tandog an, Ankara 06100, Turkey.
E-mail: alpbaz@eng.ankara.edu.tr

ACKNOWLEDGEMENTS The manuscript was received 11 January 2002 and accepted for
The authors gratefully acknowledge Ankara University Research Fund publication after revision 11 July 2003.
and Biotechnology Institute for providing Ž nancial support.

Trans IChemE, Vol 81, Part C, December 2003