Exploiting Fluorescent Reporter Molecules for Process Analytical Technology (PAT)

Process Analytical Technology (PAT) launched by the U.S. Food and Drug Administration (FDA) aims to ensure the quality of pharmaceutical products. One important tool to obtain a deeper process understanding is the use of modern real-time process sensors and analyzers. In this context an industrially accepted optical probe for turbidity measurement (Aquasant probe) has been adapted for on-line and real-time fluorescence measurement in (bio-)reactors. By tagging product proteins with fluorescent reporter molecules (e.g. GFP) it was possible to quantify product concentrations during a fermentation process with the new probe. The on-line obtained signal showed a high correlation to the off-line signal. This new method has remarkable advantages compared to classical off-line product lab analyses and can serve as a platform-independent quantification method of products to be used in either up- or downstream processing.