In bioprocesses, living cells are used to produce biological materials of interest. Perhaps the most well‐known product produced in bioprocesses is penicillin. Implementing process analytical technologies (PAT) in bioprocesses in terms of quantitative measurements using vibrational spectroscopy is important, but also challenging. In comparison to chemical processes in general, bioprocesses can be described as very complex, where numerous constituents play a vital role within the cells as well as outside the cells. Although bioprocess engineering relies on utilising the natural or genetically modified behaviour of the cultivated organism or organisms, what is optimal for the well‐being of the organism is not necessarily optimal for the production of the compound of interest. Therefore, the organisms’ environment needs to be monitored and controlled. In bioreactors, this is a fairly straightforward task when it comes to parameters such as pressure, temperature, dissolved oxygen and pH. However, this is not the case when it comes to the important chemical composition of the organisms’ environment, or for that matter, the intracellular constituents. For monitoring the chemical environment, vibrational spectroscopy is a very versatile and thereby very interesting method.
Quantitative measurements in bioprocesses using mid or near infrared spectroscopy typically require multivariate calibration methods and a significant amount of calibration data on which to base the model. Collecting calibration data is, in turn, usually a very tedious process. However, even when a sufficient amount of calibration data is available and a multivariate method is used, there is no guarantee that the obtained accuracy is sufficient for the intended measurement application. Therefore, two challenges for implementing quantitative measurements in bioprocesses can be easily identified: (1) How can the time spent on collecting calibration data be reduced, and (2) What mathematical methods can be used to increase the accuracy of the calibration model? These questions are also addressed in this thesis. This is done by evaluating the impact of the methodology used in applications of quantitative measurements on Pichia pastoris, Streptomyces peucetius, and anaerobic digestion processes. In general, the methodologies used produced promising results.
|Publication status||Published - 2018|
|MoE publication type||G5 Doctoral dissertation (article)|