Flow bioprocess control

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. 

Flow-injection analysis (FIA) has gained tremendous importance for bioprocess control during the last few years [23-27], Although this is not an in situ or a real on-line analytical technique, it can be automated and operated at very high analysis cycle frequencies (quasi online). One of the most important advantages of FIA is the use of very small sample volumes. 

Hitzmann, B., Gomersall, R., Brandt, J., van Putten, A. (1995) An expert system for the supervision of a multi channel flow injection analysis system. In Recent Advances in Biosensors, Bioprocess Monitoring, and Bioprocess Control, K.R. Rogers, A. Mulchandani, W. Zhou, Eds., ACS Symposium Series, American Chemical Society, Washington, D.C. (this vol.)... 

Chapters 9-16 cover the application of optical and biosensor methods for on-line monitoring and control of bioprocesses. Topics include the use of expert systems for controlling flow injection analysis systems and hybrid process modeling for bioprocess control. 

Flow-based arrangements have been extensively investigated and widely adopted for the determination of soluble reactive phosphorous (SRP) in environmental samples. Flow-based systems for SRP have been successfully used in shipboard determinations [69,73,76,94,95], in situ analysis of streams [107], in field monitoring and control of phosphorus removal in wastewater treatment plants [71,90,100,108,109] and also in other bioprocesses control and land-based laboratory applications. 

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. 

Schmidt HL (1993) Biosensors and flow injection analysis in bioprocess control. J Biotechnol... 

Hagman and Sivertsson discussed the work performed at Pharmacia and Upjohn52 on monitoring and controlling bioprocesses. They followed the protein production-derived form Chinese hamster cells (CHO-cells) in a 500-1 reactor over a 3-month period. The diagrams of the flow cell and pumping/NIR system are displayed, and the logic behind the work outlined. External and on-line calibrations were performed. 

Thermal Mass Flowmeters The trend in the chemical process industries is toward increased usage of mass flowmeters that are independent of changes in pressure, temperature, viscosity, and density. Thermal mass meters are widely used in semiconductor manufacturing and in bioprocessing for control of low flow rates (called mass flow controllers, or MFCs). MFCs measure the heat loss from a heated element, which varies with flow rate, with an accuracy of 1 percent. Capacitance probes measure the dielectric constant of the fluid and are useful for flow measurements of slurries and other two-phase flows. 

In this study, after a brief introduction to PI we provide the bases of a technique for the preparation of polymeric micro-porous materials, known as polyHIPE polymers (PHPs) which are now used extensively in PIM, and micro-reactor technology. These polymers are prepared through the high internal phase emulsion (HIPE) polymerization route. In order to control the pore size, the flow-induced phase inversion phenomenon is applied to the emulsification technique. The metalization of these polymers and formation of nano-structured micro-porous metals for intensified catalysis are also discussed. Finally, we illustrate the applications of these materials in chemical- and bioprocess intensifications and tissue engineering while examining the existence of several size-dependent phenomena. 

The continuous generation of heat by microbial cultures can also be used as a basis for an on-line monitoring of the microbial activity and metaboUsm. If the temperature increase in the cooling water, its flow rate, and the other relevant energy exchange terms such as agitation and evaporation rates are measured systematically, the heat dissipation rate of the cellular culture can quantitatively be monitored on-line in industrial fermenters. The information contained in this signal can be used to optimize the bioprocess and for on-line process control. 

Lai, J. J., Nelson, K. E., Nash, M. A., Hoffman, A. S., Yager, P. and Stayton, P. S. (2009) Dynamic bioprocessing and microfluidic transport control with smart magnetic nanoparticles in laminar-flow devices . Lab on a Chip, 9,1997-2002. 

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