Precise fed-batch bioreactor monitoring with Bronkhorst mass flow control and fermSYS – VOC sensors

In fed-batch-based bioprocesses, the precise monitoring of working volume and biological activity is crucial. In collaboration with Bronkhorst and the Westphalian University of Applied Sciences in Recklinghausen, it has been demonstrated how the combination of non-invasive headspace pressure measurement and the fermSYS VOC sensor system makes metabolic phase transitions visible in real time without the need for sampling.

The challenge

In fed-batch processes, the liquid volume changes continuously as a result of the continuous addition of culture medium. For precise process control and mass balance, this working volume must be tracked accurately. At the same time, in practice, the metabolic activity of the organism (e.g. yeast) is often still determined via time-delayed offline sampling, which makes it difficult to respond directly and automatically to changes in metabolism.

The approach

An integrated test setup at the Westphalian University of Applied Sciences in Recklinghausen combines two complementary technologies:

1. Volume tracking via headspace differential pressure: A Bronkhorst Flexi-FLOW measures volume effects in the bioreactor by detecting minute changes in pressure.

2. Real-time metabolism via VOC sensors: The fermSENSE-CUBE VOC sensor system continuously measures the concentration of ethanol and volatile compounds in the exhaust gas as a direct indicator of biological activity.

Figure 1: Schematic diagram of the bioprocess setup for yeast, including the Bronkhorst headspace volume system and a fermSYS VOC sensor

The results

1. Precise phase identification: During yeast growth (Saccharomyces cerevisiae), the fermSYS VOC sensor system accurately indicated the transition to the diauxic phase (change in substrate metabolism).

2. Explanation of deviations: Deviations in the physical headspace volume model could be directly explained and correlated with increased biological gas production during the peak growth and diauxic phases.

3. No sampling required: Exhaust gas monitoring provides continuous signals without disrupting the reactor environment or compromising sterility.

Fig. 2: The headspace volume measured during the yeast growth bioprocess (grey, Bronkhorst MFC) compared with the measured ethanol production (orange, fermSYS VOC sensor).

Practical conclusions

Combining intelligent gas flow measurement with the fermSYS VOC exhaust gas sensor system enables a deeper understanding of the process and lays the foundation for fully automated, real-time feeding or aeration strategies at laboratory and pilot scale.

Seamless integration with fermHUB

Implementation is made even easier with our fermHUB data platform: both the VOC sensors and the Bronkhorst mass flow controller can be operated via a single software package using a plug-and-play approach. This allows you to consolidate the entire process management within a single system – from centralised data collection and direct actuator control, through the reuse of historical run data, right through to automated operation via the Golden (Fed) Batch Autopilot.

Areas of application

The combination of fermSYS VOC sensor technology (exhaust gas metabolite tracking) and precise gas flow and pressure control is particularly well suited to the following scenarios:

• Automated feed or aeration control (feedback control): Real-time dosing of substrates or feed air in fed-batch-based processes (e.g. to prevent Crabtree effects or methanol/ethanol toxicity).

• Identifying metabolic phase transitions: Contactless identification of substrate changes (e.g. diauxic growth) and metabolic effects without the need for time-delayed offline sampling.

• Monitoring of foam and gas formation: Early detection of unexpected surges in outgassing or excessive release into the headspace.

• Non-invasive bioreactor volume tracking: Continuous monitoring of the liquid volume solely via the gas phase – without the need for any additional sensors in the culture medium, which reduces the cleaning workload and eliminates the risk of fouling or scaling on sensors in the medium.

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