Dieses Kapitel beinhaltet: Allgemeine Betrachtungen Beschreibung des kleinsten Bioreaktors Leistungseintrag in Kolbenreaktoren Sauerstofftransferraten (OTR) in Kolbenreaktoren

In this paper, the development of a laboratory experiment for teaching bioprocess control and automation is presented. In bioprocesses, chemical reactions are performed by living microorganisms, which do not only show increased metabolic needs and certain environmental susceptibilities, but also offer huge advantages like highly sophisticated capabilities for synthesizing complex protein products in a reliable, fast, cheap, and safe manner. Therefore also the plants to be used for bioreactions exhibit, compared to conventional process technology, additional demands e.g. with respect to sterility or aeration. The corresponding lecture intentionally focuses on modern geometric [and] model-based control. As the dynamics of a bioprocess depend on the characteristics of the microorganisms' metabolism as well as on some mechanical properties of the bioreactor used, a bioprocess model constitutes of two parts: a kinetic model of the microorganisms, and a reactor model. This paper, as a first in a series of three, focuses on the latter, including the experimental procedures for identification of the four most important characteristics of a bioreactor, which are power input, homogenization, and gas and heat transfer. Considerations on scale-up of the reactor system increase comprehension of the model. A short description of the control system used, a portable low-cost host-target real-time computer system completes this experiments' hardware documentation. One distinctive feature of the control system is its newly developed graphical user interface. This interface was programmed in Labview and relieves operation of the plant as it does not fall short of commercial ones in any way thus well-prepares students for a latter job. Concomitant papers will in detail describe the kinetic model and the didactic design of the instructions for the experiment.

Cell concentration is one of the key parameters to be monitored during cell cultivation processes. This is very often done off-line by sterile sampling and subsequent counting using a hemocytometer or an electronic cell counter. A direct optical measurement of cell density via an in situ microscope (ISM) eliminates the need for sampling and allows for continuous monitoring of this key parameter. Two such systems have been described in the literature, one of them has been developed at Mannheim University of Applied Sciences. This system has the advantage of not using any moving mechanical parts within or outside the fermentation vessel. Here we show two examples of advanced applications of a new version of this ISM with unprecedented resolution and frame rate: Adaptation to double glass jacket equipped bench top reactors and longer term application in a perfused 30 L steel reactor. Results in both cases show the performance of the ISM, the comparability of cell culture data obtained by ISM and traditional methods and the potential for further development of the ISM.

This second paper on the development of a biotech teaching experiment focuses on the bioprocess itself: After identification of requirements of a bioprocess to be suited for a laboratory experiment for students, the mathematical models of the chosen process are presented in detail for batch, fed-batch, and continuous mode of operation. Linearization of the nonlinear dynamics reveals the system neither to be completely controllable nor to be completely observable – with biological reasons and solutions to this problem given. For fed-batch operation, the capabilities of the Simulink simulation environment to simulate different feeding strategies are shortly depicted. With specially tailored learning materials (“from students for students”), mastering the differences between “nice” simulation data and real-world sensor signals is addressed. Some comments on the development of an adapted strain of the microorganisms to the medium as the basis for a successful fermentation execution conclude this paper.

Monitoring of microbiological processes using optical sensors and spectrometers has gained in importance over the past few years due to its advantage in enabling non-invasive on-line analysis. Near-infrared (NIR) and mid-infrared (MIR) spectrometer set-ups in combination with multivariate calibrations have already been successfully employed for the simultaneous determination of different metabolites in microbiological processes. Photometric sensors, in addition to their low price compared to spectrometer set-ups, have the advantage of being compact and are easy to calibrate and operate. In this work, the detection of ethanol and CO2 in the exhaust gas during aerobic yeast fermentation was performed by two photometric gas analyzers, and dry yeast biomass was monitored using a fiber optic backscatter set-up. The optical sensors could be easily fitted to the bioreactor and exhibited high robustness during measuring. The ethanol content of the fermentation broth was monitored on-line by measuring the ethanol concentration in the fermentation exhaust and applying a conversion factor. The vapor/liquid equilibrium and the associated conversion factor strongly depend on the process parameter temperature but not on aeration and stirring rate. Dry yeast biomass was determined in-line by a backscattering signal applying a linear calibration. An on-line balance with a recovery rate of 95–97% for carbon was achieved with the use of three optical sensors (two infrared gas analyzers and one fiber optic backscatter set-up).