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Bioprocess Monitoring and Control
Bioprocess monitoring and control is crucial to maintain an optimal cellular environment within bioreactors. There are several key parameters which influence culture growth and product formation. They include pH, dissolved oxygen (DO), temperature, as well as the concentrations of nutrients and byproducts. These process parameters are monitored using sensors, and control strategies are implemented, to maintain the parameters within a specified range. However, designing an effective bioprocess control strategy can be complex and involve a number of important considerations. These include decisions on the control loop design, the types of sensors, and the bioprocess control software. Here, you can find expert knowledge on the optimization of bioprocess monitoring and control strategies
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Why is bioprocess monitoring and control important?
Monitoring and controlling critical process parameters is needed to create a culture environment that ensures maximum productivity. For this to be achieved, key parameters and their setpoints should be identified and incorporated into the bioprocess design. This allows for product yield and quality to be maximized in a reproducible manner, which is important to minimize costs for raw materials, avoid failed batches, and as a result be time- and cost-efficient.
How does bioprocess monitoring and control work?
Optimal bioprocess control is achieved using feedback control loops. Here, the sensors within these loops continuously monitor the system’s response, providing automated parameter control without the need for human intervention. Get an overview on bioprocess monitoring and control in our webinar.
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What are feedback control loops? And how can these improve bioprocess monitoring and control?
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.
Which process parameters can be controlled with a feedback control loop?
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.
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How are parameters monitored in real-time?
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.
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How and why are parameters monitored offline, after taking a sample?
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 -either manually or automatically- at regular 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.
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Which parameter setpoints should I use for my process?
Unfortunately, there is no general answer to this, but the ideal setpoints will depend on the organism or cell type being cultured and your specific application.
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Which bioprocess parameters are relevant?
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
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Eppendorf solutions for streamlined bioprocess monitoring and control
The Eppendorf bioprocess systems help you optimizing your process monitoring and control strategy and be as flexible as possible. They facilitate the use of various sensor types from different vendors. The Eppendorf bioprocess control software packages facilitate development of tailored control strategies.
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With Eppendorf bioprocess systems and software* you can
- Use analog as well as digital Mettler Toledo ISM® and Hamilton ARC® sensors
- Use optical as well as electrochemical and polarographic sensors for pH and DO, respectively
- Seamlessly integrate various sensor types
- Develop scripts for tailored process control loops
- Benefit from software features for simplified sensor calibration and judgement of sensor health
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*compatible sensor types and software features may vary between the bioprocess systems
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Download protocols
Here you find practical help on the use and calibration of sensors.
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