On-line infrared spectroscopy for bioprocess monitoring

Abstract

One of the major aims of bioprocess engineering is the real-time monitoring of important process variables. This is the basis of precise process control and is essential for high productivity as well as the exact documentation of the overall production process. Infrared spectroscopy is a powerful analytical technique to analyze a wide variety of organic compounds. Thus, infrared sensors are ideal instruments for bioprocess monitoring. The sensors are non-invasive, have no time delay due to sensor response times, and have no influence on the bioprocess itself. No sampling is necessary, and several components can be analyzed simultaneously. In general, the direct monitoring of substrates, products, metabolites, as well as the biomass itself is possible. In this review article, insights are provided into the different applications of infrared spectroscopy for bioprocess monitoring and the complex data interpretation. Different analytical techniques are presented as well as example applications in different areas.

Optimization of Insect Cell Based Protein Production Processes - Online Monitoring, Expression Systems, Scale Up

“…However, there is still a strong demand for monitoring various other parameters of interest e.g. medium components, product concentration as well as cell density and viability, which allow a deeper understanding and insight into manufacturing processes [39]. Despite the increasing demand for a high and consistent product quality in the biopharmaceutical industry and the high potential for process improvement, available in situ monitoring techniques have been rarely established for insect cell culture processes.…”

“…Gaining information about these parameters usually requires sampling from the bioreactor for offline analysis. However, major drawbacks of this approach are the time delay between sampling and analysis as well as the risk of contaminations [39]. In order to avoid these concerns, an in situ monitoring system can be applied to facilitate real time measurement directly in the bioreactor or in a bypass [41].…”

“…Spectroscopic methods such as the near infrared (NIR) spectroscopy and mid Compared to the NIR signal, the MIR signal provides more defined peaks in the absorption spectra which facilitates a better assignment of molecules [39].…”

“…Further potential analytes are proteins with their N-H bonds as well as O-H bonds of alcohols and C-H bonds of aliphates and aromates [39]. The possibility of utilizing IR spectroscopy for in situ applications in bioprocess monitoring was facilitated by the development of attenuated total reflectance (ATR) probes.…”

Application of Quality by Design Paradigm to the Manufacture of Protein Therapeutics

“…Several analytical methods that have the ability of tracking single components in bioreactors are currently being explored. Some of the most promising technologies are based on infrared spectroscopy, and have been reviewed recently by Landgrebe et al [104]. Successful implementation of these techniques may lead to absolute online monitoring and process control.…”