In this interview, News-Medical speaks with Tony Kou from Thermo Fisher about how real-time respiratory gas analysis is improving fermentation and cell culture monitoring across biopharma development and manufacturing. They discuss the value of continuous process data for optimizing culture performance, supporting process analytical technology (PAT) strategies, and accelerating the path toward more automated bioprocessing.
Can you briefly introduce your role at Thermo Fisher Scientific and the biopharma applications you support?
I’m a Senior Applications Specialist; I mainly review customer applications and determine the best system configurations based on project requirements. I rely on my technical knowledge and customer application data to make sure the recommended solution is the right fit.
What are the biggest monitoring challenges in fermentation and cell culture today, especially as teams move from process development to manufacturing?
One of the main challenges when scaling up is understanding how different practical requirements affect the fermentation process. For example, while powdered media can be added directly at the R&D and pilot scale, manufacturing often requires the media to be dissolved into a liquid first so it can be pumped into the fermenter.
Why is off-gas analysis such a valuable window into what is happening inside a fermenter or bioreactor?
With off-gas analysis, users can monitor the process in real time and make adjustments to agitation speeds, feed rates, and other important settings as needed. This helps reduce the number of runs required to optimize yields and can quickly identify problems like dying microbes, contamination, or toxic conditions so additional time, effort, and resources aren’t wasted.
How can respiratory gas measurements help scientists better understand culture health, growth kinetics, and substrate consumption?
Tracking respiratory gases gives users a better understanding of how their culture is performing. It provides valuable insight into cell health, growth rate, and nutrient consumption, while also helping identify whether the culture has the right conditions to produce the product of interest or if issues like toxic byproducts are limiting growth.
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What do measurements such as oxygen uptake rate (OUR), carbon dioxide evolution rate (CER), and respiratory quotient (RQ) tell teams about metabolic activity and process performance?
OUR, CER, and RQ add another layer of information that other measurements can't provide. While optical density gives a rough estimate of total cell count, it can't distinguish between live versus dead cells. That's where OUR comes in. Its correlation with cell viability helps provide a much clearer picture of what's happening during the process.
Can you share an example of how real-time gas analysis can help teams make better process decisions, such as nutrient feeding, endpoint determination, or deviation response?
An R&D facility in South San Francisco usually has hundreds of experiments that are running at the same time; real-time off-gas analysis allows their scientists to quickly identify experiments that aren't worth continuing.
This frees up time to focus on the most promising conditions and allows the equipment allocated to the low-potential experiments to be turned around for the next set of experiments while the current batch is still finishing.
What advantages does continuous process mass spectrometry offer compared with relying only on offline sampling or less frequent measurements?
Monitoring off-gases with a process mass spectrometer not only saves time and reduces manual effort, but also gives users real-time information so they can adjust as needed. Because the system analyzes the off-gases instead of directly sampling the culture, the risk of contamination is virtually eliminated.
What should teams consider when implementing respiratory gas monitoring across lab-scale, pilot-scale, and production-scale workflows?
When rolling out a program across different workflows, particularly at multiple sites/geographic locations, making sure the analyzers used are both accurate and precise is key. Otherwise, comparing results equates to comparing apples and oranges.
How can real-time process monitoring support PAT strategies in biopharma development and manufacturing?
Real-time process monitoring speeds up PAT implementation by providing immediate insight into process changes. Without it, detecting shifts in critical process parameters and when to intervene often comes down to “educated guessing and checking”.
How do you see advanced analytics and real-time process data shaping the future of biopharma process optimization and control?
To me, advanced analytics and real-time process monitoring are key building blocks for full automation. Automating more of the process can reduce human error, improve efficiency, lower costs, and speed up time-to-market.
For teams just beginning to explore real-time respiratory gas analysis, what is one piece of advice you would give them?
Take advantage of the knowledge and experience within the fermentation community. I've found that people are incredibly open to sharing their experiences and lessons learned, and they're genuinely excited to see fermentation-based products succeed.
About the Speaker
Tony Kou is a Senior Applications Specialist at Thermo Fisher Scientific and a global subject matter expert in process mass spectrometry applications. With more than 13 years of experience supporting Thermo Scientific process monitoring technologies, Tony helps evaluate analytical feasibility, measurement strategies, and calibration requirements for process mass spectrometry systems. His background spans application science, business development, field service, analytical chemistry, and biotechnology-focused process monitoring. Tony holds a degree in microbiology from the University of California, Davis.
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