Bioprocess Monitoring and Control

There are several key parameters which are typically monitored in a bioprocess, including

• Physicochemical parameters, like pH, dissolved oxygen (DO), temperature
• Nutrient concentrations, such as glucose and glutamine
• Byproduct concentrations, such as lactate and ammonia
• Information about the culture, such as biomass, viability, product concentration
• Parameters relevant for conducting the bioprocess, such as liquid level and foam formation

Find more detailed information about why and how to monitor and control some of them on our websites on DO control in bioreactors and pH control in bioreactors . See our process analytical technology website for some examples of glucose control in bioreactors.

Real-time measurements are conducted in-process, providing continuous monitoring to improve accuracy and efficiency. This can be achieved using either on-line or in-line techniques. For in-line measurements, the sensor is placed directly inside the bioreactor to measure the parameter in situ. With on-line measurements, the sample is usually diverted into a by-pass stream, where automatic measurements are taken by the sensor. Process Analytical Technology (PAT) can be implemented into bioreactor systems to provide in-line or on-line bioprocess monitoring. Despite its benefits, real-time bioprocess monitoring and control has only been optimized for a limited set of parameters, including pH, temperature and DO. This technology is less routine for other parameters including cell density, cell viability and metabolite concentrations.

Sometimes, the sensor technology for real-time monitoring is not available or is unsuitable for the bioreactor system in use. In this case, process parameters can be monitored offline. For this, samples can be taken from the bioreactor at regular intervals. This can be done either manually or automatically using an autosampler . The latter can help obtaining strong datasets by facilitating sampling 24/7 in regular, short intervals. Process parameters that are often monitored offline include cell viability, product concentration, and byproduct concentrations. Offline monitoring can still be used for process control. For example, offline nutrient concentration readings can be used to manually calculate and administer the volume of feed required to maintain optimal nutrient levels.

Yes, this is possible when using appropriate bioprocessing software solutions such as DASware^® control and BioNsight^® cloud from Eppendorf. In this example, sensor data recorded in the bioprocess control software DASware control can be transferred to our cloud solution BioNsight cloud in real time and accessed from anywhere. This allows remote monitoring of your bioprocess.

Feedback control loops are used to control process parameters at setpoint. Essentially, these involve the use of sensors that monitor process parameters, transmitting the recorded value to a bioprocess control software integrated into a bioprocess control system. Together, the bioprocess control software and system regulate actuators, which can be for example pumps, valves, or drives, to adjust the parameter back to its optimal level. Feedback control loops are preferred over non-feedback systems, as the sensors within these loops continuously monitor the control system’s response, providing automated parameter control without the need for human intervention.

In principle, any! However, a prerequisite of parameter control using feedback loops is the availability of a sensor that monitors the parameter of interest in real-time and is integrated with bioprocess control software. Sensors for temperature, pH, DO, redox, CO₂, and level are seamlessly integrated routinely, but other sensors can be integrated as well, including those to control the concentration of nutrients in the culture and those to analyze the exhaust composition.

Read more about feedback control loops for automated culture feeding in our ebook !

Find more detailed information about why and how to monitor and control pH and the dissolved oxygen concentration (DO) on our websites on pH control in bioreactors and DO control in bioreactors .

There is no general answer to this, as the ideal setpoints will depend on the organism or cell type being cultured and your specific application. For more detailed information about cell culture in bioreactors , stem cell bioprocessing , bacterial fermentation , and yeast fermentation , please refer to application examples and expert advice from our customers and our applications team.