Fundamental Bioengineering

14Real-Time Measurement and Monitoring of Bioprocesses

Bernhard Sonnleitner

Summary

We need to substantially improve our understanding of production biosystems and processes in order to ensure a desired quality performance of (bio-)products. An absolute prerequisite for a better understanding is information and knowledge. This must be created and extended by timely quantitative analysis of the processes, and all this requires process analytical tools, data evaluation algorithms, and adequate models as well as clever process control. The state-of-routine monitoring items established in the bioprocess industry and some important state-of-the-art methods are described and potential pitfalls discussed. Physical and chemical variables such as temperature, pressure, weight, volume, flow rates, pH, redox potential, gas partial pressures in the liquid and molar fractions in the gas phase, infrared spectral analysis of the liquid phase, and calorimetry over an entire reactor are important aspects. Both classical and optical sensor versions are addressed. Biomass and bioactivity monitoring by turbidity, permittivity, in situ microscopy, and fluorescence is analyzed. Instrumental analytical tools and interfaces to bioprocesses are explained, such as chromatographic methods, mass spectrometry, flow and sequential injection analyses, field-flow fractionation, and flow cytometry.

14.1 Introduction

What we can measure or monitor in bioprocesses are the variables (or state variables), such ...