Bioreactor monitoring

As already discnssed, intrinsic LIF bioreactor monitoring is the most common application within biopharmaceutical manufacturing. Other extrinsic PAT LIF methods are also possible for biopharmacenticals snch as varions flnorescence immunoassays facilitated by flow injection analysis " or other real-time approaches. As PAT begins to emerge within biopharmaceuticals the wider used of sensitive and precise in-line intrinsic and extrinsic approaches such as optodes and at-line extrinsic methods is likely to occnr. ... 

In this review, it is described how the electronic noses are applied to on-line bioreactor monitoring for meeting the requirement of non-invasive real-time measurement and facilitating rapid and safe data generation from microbial and cell cultivations. 

Particularly when applied to bioreactor monitoring the electronic noses require high quality sensors with long and stable operation, efficient signal processing and evaluation methods, and practical interfacing with the bioreactor. The currently used sensor types and evaluation methods are summarized below. 

During bioreactor monitoring regular recalibration or checking of performance is necessary. 

Keywords discrete estimation, nonlinear estimation, bioreactor monitoring. 

The measurement of analyte concentration is a critical part of successful bioreactor monitoring. Although strategies exist for measuring the majority of relevant analytes, industrial online bioreactor control is carried out primarily by measurement and control of temperature, pH, d02, CO2, and, in some cases, cell density. This is because the available technology cannot be easily and inexpensively adapted to measure the analyte in an aseptic manner and measurement is not often achieved in real time so that online control is challenging. Biosensors for a variety of applications for... 

He, M., Lorr, D., and Wang, N. S., Near-infrared spectroscopy for online bioreactor monitoring, presented at the 1993 AIChE National Meeting,... 

Mandenius CF (1999) Electronic noses for bioreactor monitoring. Advances in Biochemical Engineering/Biotechnology 66 65-82. 

JuHen C, Whitford W. Bioreactor monitoring, modeling, and simulation. Bioprocess International 2007 2007 10-17. 

Calorimetry has been successfully applied to bioreactor monitoring and to bioprocess control. Because heat production rate is associated with the growth of most of the organisms, direct calorimetry is based on the quantification of the heat flow rate that has to be removed from the reactor to keep the system at a constant temperature. Under the condition of well controlled environment, the measurement of the heat flow rate removed is not only a qualitative indicator but a quantitative measure of the biological activity. 

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