Biotechnology: Monitoring Bioprocesses with PTR-MS

On-line monitoring of bioprocesses

IONICON PTR-MS systems can analyze the trace gas concentrations of volatile metabolites in the off-gas of bio-pharmaceutical fermentations in real-time. This very relevant process-related information can be used for on-line process monitoring and process control.

Biotechnology: Monitoring Bioprocesses with PTR-MS

Image Credit: Ionicon Analytik Ges.m.b.H.

On-line monitoring in the biopharmaceutical industry

Biotechnological fermentation processes produce modern biopharmaceutical drugs. The relevance of observing these processes is increasing, particularly in the manufacturing industry to facilitate cost-efficient production.

Historically, off-line analysis has been generally utilized to monitor biotechnical processes, which is cost and labor intensive, offering results too late for corrective action to be taken. IONICON PTR-MS can offer highly practical process data on-line and in real-time.

Volatile organic compounds (VOCs) are generated as metabolic by-products of microbial production and growth in a bioreactor. Utilizing PTR-MS to analyze these emitted volatile metabolites in a bioreactor’s off-gas in real-time provides information about the activity of the micro-organisms that can be used for process control and quality assurance.

Up to 70 VOCs were found in E. Coli fermentations with significant variations and substantial concentrations over time. The figures display noteworthy examples of this.

Biotechnology: Monitoring Bioprocesses with PTR-MS

Image Credit: Ionicon Analytik Ges.m.b.H.

Process monitoring – PTR-MS setup

Wide-ranging research projects have been performed by IONICON in the frame of the Austrian Center for Industrial Biotechnology (ACIB), where, in collaboration with distinguished organizations in the biotech sector, the capabilities of on-line process monitoring has been investigated.

The quantitative and efficient sample transfer to the PTR-MS is highly important in this context. IONICON has designed an enhanced coupling system for biotech applications, see figure, which offers automated calibration for quality assurance, multiplexing, safety measures, and dilution of the sample gas.

The complete system, comprising of the purpose-built coupling system and the IONICON PTR-MS, proved to be highly robust. It has been up and running at various industrial test sites for many years.

IONICON offers an integrated PTR-MS bio system, designed for the biotech field, as part of its customized PTR-MS solutions.

Biotechnology: Monitoring Bioprocesses with PTR-MS

Image Credit: Ionicon Analytik Ges.m.b.H.

Approach for advanced bioprocess monitoring with PTR-MS

A wide variety of volatile metabolites can be monitored utilizing IONICON PTR-MS systems.

An example of the results from three fermentations in relation to reproducibility is displayed in the figure. This is only viable when the parameters of three cultivations are carefully kept the same. Tiny deviations, accidental or intentional, are mirrored in the measured concentrations of one or more markers.

The monitoring of bioprocesses with PTR-MS can be utilized as a technique for on-line quality assurance, even with no prior knowledge of the measured VOCs’ metabolic relationships.

This kind of direct monitoring method is an element of the Process Analytical Technology (PAT) which is suggested by the US Food and Drugs Administration (FDA) to enhance efficiency, quality, and safety in drug manufacturing procedures.

Biotechnology: Monitoring Bioprocesses with PTR-MS

Image Credit: Ionicon Analytik Ges.m.b.H.

Process control and optimization

An understanding of the underlying system enables monitored signals to be directly correlated to metabolic activity. This has been shown by Luchner at al. The deviation in distinct signals can be utilized to identify a metabolic overload of the cells. This allows for prominent developments regarding advanced process control.

Biotechnology: Monitoring Bioprocesses with PTR-MS

Image Credit: Ionicon Analytik Ges.m.b.H.

IONICON PTR-MS systems in GMP production

After successful testing of research fermentations, the IONICON PTR-technology has  made another advancement where it has been used for real-time process monitoring in an industrial, GMP (Good Manufacturing Practice) controlled fermentation process.

PTR-MS has been introduced to this highly regulated area through the ability to monitor volatile microbial metabolites non-invasively in the off-gas, with no requirement to adapt the existing process.

Biotechnology: Monitoring Bioprocesses with PTR-MS

Image Credit: Ionicon Analytik Ges.m.b.H.

About Ionicon Analytik Ges.m.b.H.

IONICON Analytik was founded 1998 as a spin-off company of the University of Innsbruck, Austria commercializing an innovative technology called Proton Transfer Reaction - Mass Spectrometry. Since then we have been improving this leading-edge technology resulting in the development of several types of ultra sensitive high resolution online mass spectrometers for monitoring and quantification of volatile organic compounds (VOCs) in sub-pptv level concentrations.

Today we are the world’s leading producer of trace gas analyzers with market-leading, real-time, single-digit pptv-level detection limits using the unique Proton Transfer Reaction – Mass Spectrometry (PTR-MS) and Selective Reagent Ionization – Mass Spectrometry (SRI-MS) technology. Our product portfolio includes quadrupole MS and time of flight MS based instruments, air monitoring solutions and custom built TOF-MS, complemented by our own range of trace calibration devices and accessories.

We developed our own "ioniTOF" time-of-flight (TOF) mass spectrometer platform that we produce in-house for our PTR-TOFMS series instruments and APi-TOF systems. We also strive to let others benefit from our customizable, affordable ioniTOF ecosystem for research and OEM applications.

Since 1998, we are serving our customers in many different application areas including atmospheric chemistry, environmental research and trace gas analysis (e.g. emissions in urban and remote areas, indoor spaces, vehicles), food and flavour science (e.g. analysis of coffee, olive oil, butter, cheese, wine, herbal extracts and aromas), industrial VOC monitoring (e.g. in waste incineration plants, chemical factories and production sites of the semiconductor industry) and illicit substances detection (Explosives, CWAs, TICs). A special focus was given to medical and biotechnological applications where real-time monitoring of industrial fermentation processes, of synthetic gas production processes in the petrochemical industry and real-time breath gas analysis in clinical settings are carried out.

We also offer analytical services and are an active contributor to numerous international scientific research and training projects.

In 2018 we proudly celebrated our 20th Anniversary with over 350 instruments sold. We manufacture our precision instruments at our company site located in Innsbruck, Austria.

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Last updated: Jul 15, 2020 at 9:04 AM


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