Automatic Control of Bioprocesses - Measurement, Monitoring, Modelling, and Control of Bioprocesses - page 59

different approaches are necessary. During the last 6 years (2006-2012), 97
contributions dealing with closed-loop control for fermentation processes have
been published (according to Science Direct, found by ''closed loop control'' AND
fermentation OR cultivation). However, only a minority of up to 30 applications
were actually applied to real bioprocesses; the majority were based on theoretical
applications using simulated processes.
For closed-loop control applications, in the majority of cases, a soft sensor is
combined with a PID controller to determine the feeding rate of substrate or the
specific growth rate. This approach can be combined with a forward loop, to
reduce the problems generated by the dynamics of the bioprocess. The reason why
soft sensors have attained this level of importance for control purposes is the lack
of direct measurements or their large additional expense for robust and reliable
online measurement systems.
Model predictive control has been successfully applied in other application
fields, and its importance will increase in bioprocess automation as well. However,
reliable and robust process models are required, as well as very powerful com-
puters to address the computational demands. The lack of theoretical bioprocess
models is compensated by hybrid systems combining theoretical models, fuzzy
logic, and/or artificial neural network methodology. These systems are supposed to
combine the advantages of each approach into a well-performing control strategy.
Some applications involve control of fermentations at their oxidative maximal
capacity such as the probing feeding approach or control based on the metabolic
state, tolerating small amounts of overflow metabolism. Again, both approaches
demonstrate the ability to control the system without direct measurements of
important process variables such as oxidative capacity or the metabolic state of
microorganisms.
Although many authors suggest a possible transfer of their presented control
application to other bioprocesses, the algorithms are mostly specialized to certain
organisms or certain cultivation condition as well as to a specific measurement
system. The effort required to adapt the algorithm and the required measurement
system to a specific application is still very large. Therefore, in the near future,
closed-loop control of the feeding rate or growth rate will remain a challenge.
Furthermore, as Max Planck said, ''A new scientific truth does not triumph by
convincing its opponents and making them see the light, but rather because its
opponents eventually die, and a new generation grows up that is familiar with it.''
References
1. Becker T, Hitzmann B, Muffler K, Pörtner R, Reardon K, Stahl F, Ulber R (2007) Future
aspects of bioprocess monitoring. In: Ulber R, Sell D (eds) Advances in biochemical
engineering/biotechnology vol 105. Springer, Berlin, pp 249-293. doi: 10.1007/10_2006_036
2. Navrátil M, Norberg A, Lembrén L, Mandenius C-F (2005) On-line multi-analyzer
monitoring of biomass, glucose and acetate for growth rate control of a vibrio cholerae
fed-batch cultivation. J Biotechnol 115(1):67-79. doi: 10.1016/j.jbiotec.2004.07.013