Bioreactors are key equipments in the field of biopharmaceuticals, and the real-time monitoring of their operation status is of great significance to ensure product quality and process stability. Process analytical technology (PAT), as an emerging monitoring tool, has been increasingly used in bioreactors. This paper details the technical principles and advantages of real-time PAT monitoring in bioreactors and its application research progress in actual production.

Bioreactor Reactor is an indispensable equipment in the production process of biopharmaceuticals, and its main function is to provide a suitable growth environment for microorganisms, cells, and other organisms to realize the production of target products. However, the internal environment of the bioreactor is complex, and various factors such as temperature, pH, dissolved oxygen, and substrate concentration can affect the growth and metabolism of the organisms. To ensure product quality and process stability, it is important to monitor the bioreactor operation status in real time. Process analytical technology (PAT), as a real-time monitoring means, provides strong support for process control of bioreactors.

Principles and advantages of real-time PAT monitoring technology

1. Principles of the technology

Real-time PAT monitoring techniques mainly include spectroscopy, chromatography, mass spectrometry, electrochemical analysis and other methods. These methods realize real-time monitoring of the reactor internal environment by detecting physical and chemical parameters in the bioreactor.

2. Advantages

(1) Real-time: real-time PAT monitoring technology can quickly obtain the information of the internal environment of the bioreactor and provide real-time data support for process control.

(2) Non-invasive: most of the PAT monitoring techniques do not require sampling, avoiding possible contamination and errors during sampling.

(3) Comprehensive: PAT monitoring techniques can obtain multiple parameters simultaneously, fully reflecting the internal environment of the bioreactor.

(4) Accuracy: High-precision sensors and data analysis methods make PAT monitoring results highly accurate.

Research progress on real-time PAT monitoring in bioreactors

1. Spectral analysis Techniques in bioreactors

Spectral analysis techniques include UV-visible spectroscopy, near-infrared spectroscopy, Raman spectroscopy, and so on. The application of these techniques in bioreactors is mainly focused on the monitoring of parameters such as cell density, substrate concentration, product concentration, etc.

2. Application of chromatographic analysis techniques in bioreactors

Chromatographic analysis techniques are characterized by high resolution and high sensitivity, and they are suitable for the monitoring of complex components in bioreactors. Currently, high performance liquid chromatography (HPLC) is more widely used in bioreactors.

3. Application of mass spectrometry in bioreactors

Mass spectrometry (MS) analysis technology is characterized by high selectivity and sensitivity, and it is used for on-line monitoring of the target products in bioreactors. In recent years, the application of tandem mass spectrometry in bioreactors has achieved remarkable results.

4. Application of electrochemical analytical techniques in bioreactors

Electrochemical analytical techniques have the advantages of easy operation and low cost, and they are suitable for the monitoring of pH, dissolved oxygen and other parameters in bioreactors. Currently, electrochemical sensors are increasingly used in bioreactors.

The application of real-time PAT monitoring technology in bioreactors has achieved remarkable results, which provides strong support for the biopharmaceutical production process. However, the application of PAT monitoring technology in bioreactors still faces some challenges, such as sensor stability and data analysis methods. With the continuous development of science and technology, the application of real-time PAT monitoring technology in bioreactors will be more widely used and bring more benefits to the biopharmaceutical industry.