What is Bioprocess Monitoring?

Bioprocess monitoring is the continuous or periodic measurement of critical parameters during a biological manufacturing process, such as fermentation or mammalian cell culture. These parameters may include dissolved oxygen, pH, temperature, pressure, gas flow, biomass, nutrient levels and the composition of gases leaving the bioreactor.

Effective monitoring helps manufacturers understand cellular activity, maintain optimal growth conditions, detect process deviations and achieve consistent product quality. Process Insights provides real-time gas analysis technologies that support bioprocess monitoring from laboratory development through commercial-scale production.

Why is off-gas analysis important?

Off-gas analysis measures the gases leaving a fermenter or bioreactor to provide a real-time view of cellular respiration and metabolic activity. Changes in oxygen consumption, carbon dioxide production and volatile compounds can indicate shifts in cell growth, nutrient availability, product formation or process stability.

Unlike manual sampling, off-gas analysis is continuous and non-invasive. It can help operators detect metabolic changes earlier, optimise feeding and aeration strategies, identify fermentation endpoints and improve batch consistency.

What is OUR?

Oxygen Uptake Rate, or OUR, is the rate at which cells or microorganisms consume oxygen during a bioprocess. It is commonly calculated using measurements of the oxygen entering and leaving the bioreactor, together with gas-flow data.

OUR is an important indicator of metabolic activity, biomass growth and oxygen demand. Monitoring it in real time can help identify changes in culture performance, oxygen limitations, nutrient depletion and critical process transitions.

What is CER?

Carbon Dioxide Evolution Rate, or CER, is the rate at which a biological culture produces carbon dioxide. It is calculated from the difference between the carbon dioxide concentration in the inlet gas and the concentration measured in the bioreactor’s exhaust gas.

CER provides insight into cellular respiration and substrate metabolism. When monitored alongside OUR, it helps process scientists evaluate culture health, detect metabolic changes and optimise operating conditions.

What is respiratory quotient?

Respiratory Quotient, or RQ, is the molar ratio of carbon dioxide produced to oxygen consumed:

RQ=CEROURRQ = \frac{CER}{OUR}

RQ provides insight into how cells or microorganisms are metabolising nutrients. Changes in RQ may indicate shifts in the primary metabolic pathway, substrate utilisation, nutrient availability or culture condition. Because RQ can be affected by factors such as bicarbonate buffering, acid-base reactions and measurement conditions, it should be interpreted alongside other process data.

How does PAT improve pharmaceutical manufacturing?

Process Analytical Technology, or PAT, uses real-time measurements and process understanding to monitor and control pharmaceutical manufacturing. Instead of relying only on end-product testing, PAT enables manufacturers to evaluate critical process parameters and quality attributes while production is taking place.

PAT can support faster process adjustments, reduced variability, fewer failed batches, more efficient scale-up and improved product consistency. It also supports Quality by Design and continuous manufacturing by building quality into the process rather than testing it only after production.

How does mass spectrometry improve fermentation?

Mass spectrometry improves fermentation by continuously measuring multiple components in the bioreactor’s off-gas with high speed and precision. Typical measurements include oxygen, carbon dioxide, nitrogen, argon and process-specific volatile compounds.

This data can be used to calculate OUR, CER and RQ, allowing process teams to track cellular respiration and identify changes in metabolic activity. Real-time mass spectrometry can support feed optimization, endpoint detection, contamination investigation, process scale-up and improved batch-to-batch consistency. Process Insights offers quadrupole and magnetic-sector mass spectrometry systems designed for fermentation, cell culture and biopharmaceutical manufacturing.

What gases should be monitored during fermentation?

The most important fermentation gases are usually:

• Oxygen, to measure oxygen consumption and identify oxygen limitations
• Carbon dioxide, to track respiration and metabolic activity
• Nitrogen and argon, which can support gas-flow correction and mass-balance calculations
• Water vapour, to improve measurement accuracy and understand moisture conditions
• Volatile organic compounds, which may provide information about metabolites, by-products or contamination
• Process-specific gases such as hydrogen, methane, ammonia or ethanol vapour, depending on the organism and application

The required gas profile depends on the microorganism, substrate, bioreactor design and final product.

How do you monitor mammalian cell culture?

Mammalian cell culture is monitored by combining measurements from inside the bioreactor with analysis of the exhaust gas. Standard measurements include pH, dissolved oxygen, temperature, pressure, agitation and gas-flow rates. Cell density, viability, nutrient concentrations, metabolites and product quality may also be measured online, at-line or through laboratory sampling.

Continuous off-gas mass spectrometry adds non-invasive measurements of oxygen and carbon dioxide, enabling the calculation of OUR, CER and RQ. These measurements can reveal changes in cellular respiration, nutrient utilization and metabolic state without disrupting the sterile bioreactor environment.

What analytical technologies are used in upstream bioprocessing?

Upstream bioprocessing uses a combination of sensor and analytical technologies, including:

• Mass spectrometry for multicomponent off-gas analysis
• Electrochemical and optical sensors for pH and dissolved oxygen
• Raman and near-infrared spectroscopy for nutrients, metabolites and biomass
• Capacitance probes for viable biomass measurement
• Optical density, fluorescence and UV-Vis spectroscopy
• Gas-flow, temperature, pressure and agitation sensors
• Chromatography and biochemical analysers for at-line or offline testing
• Dew-point hygrometry for moisture measurement
• Process software and chemometric models for real-time analysis and control

The appropriate combination depends on the process, scale and critical quality attributes. Process Insights specializes in real-time gas and moisture analysis technologies that help manufacturers understand biological activity, improve process control and support PAT implementation.

Real-time optical analysis is only as strong as the interface between your analyzer and the process. Our GUIDED WAVE™ Sample Interfaces from Process Insights are rugged, precision-engineered probes and flow cells act as the critical “window into the process,” delivering reliable, high-quality spectral data even in the most demanding environments.

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