Bioprocess Monitoring

Heinzle, E., and Saner, U. (1991) Methodology for Process Control in Research and Development. In Bioprocess Monitoring and Control, Ed. Pons, M.N., Hanser, Munich, p. 223-304. 

Marose S., Lindemann C., Scheper T., Two-Dimensional Fluorescence Spectroscopy A New Tool for On-Line Bioprocess Monitoring, Biotechnol. Prog., 1998 14 63-74. 

Taking all these prerequisites into account, the use of chemical and physical sensors within household appliances is considerably restricted, and only a few applications are already on the market. In the field of bioanalytics, sensors are already used for bioprocess-monitoring and biomedical applications. In this area highly specific recognition processes can be used in sensors that only require a short lifespan, due to operating conditions etc. [64]. 

In a review paper devoted to the chemometrics discussed in previous citations, Shaw et al.28 go into details of the many applications of advanced chemometrics to bioprocess monitoring. Multivariate methods and numerous algorithms are explored in this work. 

V. Vojinovic, J.M.S. Cabral, L.R Fonseca, Real-time bioprocess monitoring. Part I In situ sensors. Sens. Actuators... 

St. Marose, C. Lindemann, R. Ulber, Th. Scheper, Optical sensor systems for bioprocess monitoring. Trends Biotech., 17(1), 30-34 (1999). 

In-Situ-Fluoresence-Probes A Useful Tool for Non-invasive Bioprocess Monitoring... 

High cell densities are not only a prerequisite for high productivity additionally an effective on-line control and modeling of the bioprocesses is necessary. For industrial applications, optical measurement methods are more attractive because they are non-invasive and more robust. The potential of the BioView sensor for on-line bioprocess monitoring and control was tested. For high-cell-density cultivation of Escherichia coli, maintaining aerobic conditions and removal of inhibitory by-products are essential. Acetic acid is known to be one of the critical metabolites. Information about changes in the cell metabolism and the time of important process operations is accessible on-line for optimization... 

Ulber, R. Frerichs, J.-G. 8c Beutel, S. Optical Sensor Systems for Bioprocess Monitoring Anal. Bioanal. Chem. 2003, 376, 342-348. 

It should be noted that developments in electronics and computer science have contributed significantly to the improvement of monitoring culture systems and process control. However, there are still some areas for further general improvement of cell culture bioprocess monitoring and control, such as the estimation of cell concentration in real time. Several basic texts may supplement this chapter Kilburn (1991), Schiigerl (1991, 2001), and Sonnleitner (2000). 

In every bioprocess, monitoring biomass concentration is fundamental, because usually the growth is required to be maximized. Substrate con-... 

Three different approaches are chiefly applied micro-, flow and heat flux calorimetry. Heat flux calorimetry is certainly the best choice for bioprocess monitoring (Fig. 17) [264]. In a dynamic calorimeter, the timely change of temperature is measured and various heat fluxes (e.g. heat dissipated by stirrer, or lost due to vaporization of water) need to be known in order to calculate the heat flux from the bioreaction ... 

Transferability of spectral data and models in NIR spectroscopy. This subject is an issue that is pertinent to the future use of NIR for bioprocess monitoring. Pre-processing to remove baseline shifts and noise in spectra from individual machines or direct standardisation by data transformation with a representative subset can be used to calibrate across instruments [61]. 

While these examples illustrate the role of flow cytometry in bioprocess monitoring, the analyses have been conducted off-line thus making their use in bioprocess control impractical. Recently, a portable flow cytometer - the Microcyte - [148] has been described, which due to its small size and lower cost (compared to conventional machines) allows flow cytometry to be used as an at-line technique [149]. Ronning showed that this instrument had a role to play in the determination of viability of starter cultures and during fermentation. The physiological status of each individual cell is likely to be an important factor in the overall productivity of the culture and is therefore a key parameter in optimising production conditions. 

Pons M-N (1991) Bioprocess monitoring and control. Hanser, Munich... 

Schiigerl K, Lindemann C, Marose S, Scheper T (1998) Two-dimensional fluorescence spectroscopy for on-line bioprocess monitoring. In Berovic (ed) Bioprocess Engineering Course. Supetar, Croatia, Natl Inst of Chem, pp 400-415... 

Protein patterns of whole cells by simple SDS-PAG-electrophoresis [68] have been used for a long time in strain identification. Such an analysis resolves something like 20 to 50 bands of protein groups in the order of their (apparent) molecular mass. Detailed analysis of a high number of cellular proteins is usually performed by two-dimensional electrophoresis (see Sect. 7.2 on stress response markers) e.g. for E. coli, this was done by Pedersen et al. [69]. As mentioned above, the two-dimensional technique is not suitable for routine bioprocess monitoring. 

---