PTR-MS offers interesting opportunities for monitoring of biotechnological processes. The monitoring of volatile metabolites in the off-gas of bioprocesses, promises a direct access to highly relevant process information. The development of such an application to an industrial level involves the coordinated efforts in several areas.
Academic research on lab-scale fermenters, accompanied by biostatistics, and an in-depth understanding of the underlying metabolic processes is necessary to establish volatile marker compounds for bioprocess monitoring. The development of optimized analyzers, customized interfaces to the fermenter and a level of automation for industrial use, are challenges to be overcome by device developers, such as IONICON. The access to industrial-scale fermentations and input on the requirements, such as GMP (Good Manufacturing Practice) processes, necessitates a close collaboration with partners in the biopharmaceutical industry.
IONICON, and its former subsidiary IONIMED, have been a partner in the Austrian Center for Industrial Biotechnology (ACIB) and its predecessor ACBT for several years in area 5 bioprocess-monitoring. The ACIB is a non-profit research organization and conducts top-level research in Graz, Vienna and Tyrol making use of the tools and concepts of nature for industrial production.
Monitoring of production processes in the biotech industry at present relies predominantly on off-line analysis techniques, which are time- and cost-intensive and deliver results often too late for corrective actions. The goal is to provide a tool to improve this procedure by enabling on-line process monitoring. This type of direct monitoring technique is the part of process analytical technology (PAT) initiative currently being recommended by the US Food and Drugs Administration (FDA) to improve quality, safety and efficiency in drug manufacturing processes. Using PTR-MS we can measure volatile organic compounds (VOCs) non-invasively in the off-gas air of a fermenter. These VOCs are metabolic products of microbiological activity during a fermentation process and are directly linked to the activity of the microorganisms.
In ACIB we collaborated closely with academic as well as industry partners. At the University of Natural Resources and Life Sciences, Vienna (BOKU), PTR-MS systems were used for monitoring lab-scale fermentations employing mainly E.-Coli, as well as other cells. A specialized inlet system was developed and tested, which has been optimized for analyzing trace compounds in the off-gas of multiple fermenters in parallel. This system was then employed to monitor large bioprocess reactors in collaboration with our industrial partners, Sandoz and Boehringer Ingelheim RCV.
- Gutmann, R., et al., Advanced bioprocess monitoring by implementation of Proton Transfer Reaction - Mass Spectrometry (PTR-MS) for measurement of volatile components in the bioreactor, Poster Pittcon 2012. LINK
- Luchner, M. et al., Implementation of proton transfer reaction-mass spectrometry (PTR-MS) for advanced bioprocess monitoring, Biotechnology and Bioengineering Volume 109, Issue 12, pages 3059–3069, December 2012. LINK
- Singer, W. et al., Applications of PTR-MS in Medicine and Biotechnology, American Laboratory, 2011. LINK
|Name||ACIB (predecessor ACBT)|
|Acronym||Austrian Center for Industrial Biotechnology|
|Type of funding||Austrian, COMET Program|
|Duration (IONICON part)||2010 – 2013 (ACBT: 2006-2010)|