In support of a sustainable future: How online process analytics are assisting the biofoods industry

Importance of the topic

Biobased food production—encompassing industrial enzymes, biomass-derived proteins, alternative proteins and precision fermentation—is a rapidly growing segment of biotechnology with major implications for sustainable food systems and the bioeconomy. Robust, real-time process analytics are essential to improve yield, ensure product quality, reduce cost and support scale-up from development to commercial manufacture. Gas-phase process analytics, especially mass spectrometry (MS) of fermentor off-gas, provide direct insight into cellular respiration and metabolism and therefore play a central role in process analytical technology (PAT) strategies for biofood manufacturing.

Objectives and overview of the application note

This application note explains how online process mass spectrometry can be used as an effective PAT tool in biofood production. It describes the rationale for off-gas monitoring, the benefits of magnetic sector scanning MS for multi‑fermentor environments, key derived parameters such as oxygen uptake rate (OUR), carbon dioxide evolution rate (CER) and respiratory quotient (RQ), and demonstrates performance and long‑term stability data from a Prima BT magnetic sector gas analysis MS. The focus is on practical gains for fermentation control and product quality in enzyme, biomass and precision fermentation processes.

Methods and analytical approach

• Measurement principle: Off-gas samples from fermentor headspace and sparge (inlet) lines are analyzed to quantify major air gases (O2, CO2, N2, Ar) and selected volatiles (e.g., ethanol, methanol, ammonia, H2S).
• Derived process metrics: CER and OUR are calculated from component concentrations and gas flow rates; RQ is computed as CER/OUR to indicate the predominant carbon source and metabolic state.
• PAT workflow: Identify critical quality attributes (CQAs), map the critical process parameters (CPPs) that affect those CQAs, apply continuous monitoring, and use the data to control the process (Design → Analyze → Monitor → Control).
• Case example: A fed‑batch Saccharomyces cerevisiae fermentation where cells initially consume ethanol and later switch to glucose; off‑gas MS tracked the metabolic shift with RQ stabilizing near ~1 during active glucose oxidation.

Used instrumentation

• Primary analyzer: Scanning magnetic sector mass spectrometer (Thermo Scientific Prima BT/Prima PRO family described).
• Key components and features: cold‑cathode vacuum gauge, ion source, quadrupole lens, Faraday detector, multi‑stream inlet selector for sampling many fermentors, and robust magnetic circuit providing flat‑topped spectral peaks that enable precise quantitation.
• Operational capabilities: Fast analysis cycles (~5–10 s per measurement point), compatibility with multi‑stream sampling (single MS servicing up to ~50 fermentors with a few‑minute cycle per fermentor), and long intervals between recalibration/maintenance.

Main results and discussion

• Analytical performance: A Prima BT configured to continuously analyze N2, O2, Ar and CO2 in a compressed air cylinder for seven days at a 5 s cycle demonstrated exceptional long‑term stability. Day‑to‑day mean variation for nitrogen and oxygen was ≤ ~0.005 mol% and carbon dioxide varied by ≈1 ppm day‑to‑day.
• Precision and speed: The scanning magnetic sector MS provided ppm‑level precision for CO2 and few‑parts‑per‑million precision for O2 with sub‑10‑second measurement capability—important for detecting small but process‑critical changes in gas composition during fermentation.
• Process insight: Real‑time OUR/CER/RQ monitoring detects metabolic phase transitions (lag, exponential growth, substrate switch), can identify predominant carbon sources, and supports determination of optimal harvest points or feed strategies in fed‑batch operations.
• Practical deployment: By remaining external to sterile vessels and interfacing with DCS/PLC/SCADA, gas analysis MS offers low contamination risk and straightforward integration into automated control schemes.

Benefits and practical applications

• Improved process control: Rapid detection of metabolic shifts and substrate utilization enables tighter feed control, optimized growth/product formation, and reduced batch failures.
• Quality assurance: Continuous monitoring of CPPs tied to CQAs supports consistent product attributes for enzymes, biomass proteins and precision fermentation outputs.
• Operational efficiency: Multi‑stream sampling allows a single analyzer to service many vessels, reducing capital and maintenance costs versus individual sensors per fermentor.
• Automation potential: Robust, high‑precision signals from magnetic sector MS are suitable inputs for model‑based or closed‑loop control systems to stabilize RQ or other performance metrics.

Future trends and opportunities

• Integration with digital infrastructure: Tighter coupling of high‑frequency MS data with DCS/SCADA, advanced analytics and machine learning will enable predictive control and anomaly detection at scale.
• Expanded analyte coverage: Broader volatile panels and improved sensitivity will allow concurrent monitoring of trace metabolic by‑products, enabling richer metabolic phenotyping and earlier detection of contamination or stress.
• Scalability and multi‑site deployment: High‑stability, low‑maintenance magnetic sector instruments support decentralised PAT strategies across pilot and commercial facilities.
• Regulatory and industry adoption: As sustainability and alternative protein markets expand, acceptance of gas‑phase PAT for process validation and control is likely to increase, supporting faster commercialization.
• Hybrid PAT frameworks: Combining off‑gas MS with in‑line chemometrics, soft sensors and offline analytics (e.g., HPLC, proteomics) will provide holistic process understanding.

Conclusion

Online gas analysis by scanning magnetic sector mass spectrometry is a high‑value PAT tool for biofood manufacturing. Its combination of speed, precision and long‑term stability enables actionable real‑time metrics (OUR, CER, RQ) that directly inform feed strategies, harvest timing and process control. Magnetic sector MS coupled to multi‑stream sampling offers a cost‑effective, low‑risk route to scale PAT across development and production, accelerating the sustainable deployment of enzymes, biomass proteins and precision‑fermented food ingredients.

References

1. The White House. Bold Goals for U.S. Biotechnology and Biomanufacturing: Harnessing Research and Development to Further Societal Goals. 2023.
2. The White House. Executive Order on Advancing Biotechnology and Biomanufacturing Innovation for a Sustainable, Safe, and Secure American Bioeconomy. 2022.
3. Toulhoat H. Heterogeneous Catalysis: Use of Density Functional Theory. Reference Module in Materials Engineering. Elsevier; 2016.
4. Creative Enzymes. Applications of Enzymes in the Food Industry. Industry blog/resource.
5. EUFIC. Five Trending Alternative Protein Sources to Meat in Europe. Educational article on food production and alternative proteins.