Use of Infrared Spectroscopy for the On-Line Multicomponent Analysis and Control of Bioprocesses

Abstract

Current strategies for the control of bioprocesses are based on the use of material balances to indirectly estimate the status of the culture. Until recently, direct measurements of substrate and product concentrations, other than that of gaseous components, has been hampered by the lack of sensors suitable for use in a sterile environment. However, infrared spectroscopy has been shown to be useful in the quantitation of β-lactam production in the Penicillium fermentation, pyruvate utilization in the E. coli process, and simultaneous glucose uptake and ethanol formation in the Saccharomyces cerevisiae process. This technique potentially offers the unique advantage of allowing for resolution of multiple components in the reaction mixture. Its general utility as a “bioreactor sensor” will be determined by the sensitivity and stability of the instrumental analysis, the speed and accuracy of the mathematical techniques for resolution of the spectra, and the implementation of a satisfactory sampling system. This paper will address these problems and their resolution for the on-line analysis with and use of the IR spectrophotometer in the closed-loop control of the Saccharomyces cerevisiae process.