MS Thesis Defense : Vida Rahmatnejad

Application of cells for manufacturing purposes dates back to ancient times when yeast was used to brew beer and leaven bread. However, cells were not utilized for producing medication until 1943 when Penicillium was produced as a medication using a microorganism called Penicillium chrysogenum. In recent decades biopharmaceuticals have been an effective method for treating life-threatening diseases such as HIV/AIDS as well as different types of cancer. To improve the productivity and efficiency of the manufacturing process of biopharmaceuticals, growth control of recombinant cells such as Eschericia coli is considered an essential factor. The results from several studies highlight the fact that to achieve the optimal conditions for product formation, it is crucial to control parameters such as pH, DCO₂, DO, and glucose. Information obtained from monitoring the bioprocesses could play a major role in developing appropriate control systems. The importance of process monitoring has led to developing new techniques to measure a variety of elements such as ions, substrates, and products. However, sensors are yet considered as primitive because of not being capable of monitoring the cell culture processes using reliable and precise models. Disposable small-scale cell culture vessels are widely used in studies conducted at early stages of bioprocess development as well as in academia. However, due to the lack of appropriate sensors, these vessels are not equipped with monitoring systems which makes these processes less repeatable and reliable as they are not studied from analytical point of view. FDA (Food and Drug Administration) seeks compliance in biopharmaceutical industry as well as operational control applying modern process control tools and techniques through process analytical technologies (PAT) initiative. This initiative is an indication of the fact that monitoring systems play crucial role in providing more reliable information from bioprocesses and improving the products.

This work is an effort to improve the small-scale cell culture studies by developing a prototype equipped with non-invasive continuous monitoring system for DCO₂ (featuring a sampler mounted outside the vessel) and glucose. Improvements were implemented on the original design of the CO₂ sensor and the sensor was integrated with the T-flask. The promising results from the noninvasive monitoring of DCO₂ in cell cultures in the T-flask are presented. Furthermore, future studies regarding noninvasive monitoring system for glucose as well as the application of the pH, DCO₂, DO and glucose sensors as a monitoring system of the cell proliferation, differentiation and metabolic activity of cells are discussed.