Bioprocess Monitoring and Control

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.

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 -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.

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.