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David Heinrich Müller
David Heinrich Müller

Public Documents 1
The Good pH probe: Non-invasive pH in-line monitoring using Good buffers and Raman sp...
David Heinrich Müller
Marieke Börger

David Heinrich Müller

and 3 more

July 21, 2023
In bioprocesses, the pH value is a critical process parameter that requires monitoring and control. For pH monitoring, potentiometric methods such as pH electrodes are state-of-the-art. Nevertheless, they are invasive and show measurement value drift. Spectroscopic pH monitoring is a non-invasive alternative to potentiometric methods avoiding this measurement value drift. In this study, we developed the Good pH probe, which is an approach for spectroscopic pH monitoring in bioprocesses with an effective working range between pH 6 and pH 8 that does not require the estimation of activity coefficients. The Good pH probe combines the Good buffer 3-( N-morpholino)propanesulfonic acid (MOPS) as pH indicator with Raman spectroscopy as spectroscopic technique, and Indirect Hard Modeling (IHM) for the spectral evaluation. During a detailed characterization, we proved that the Good pH probe is reversible, exhibits no temperature dependence between 15 and 40 °C, has low sensitivity to the ionic strength up to 1100 mM, and is applicable in more complex systems, in which other components significantly superimpose the spectral features of MOPS. Finally, the Good pH probe was successfully used for non-invasive pH in-line monitoring during an industrially relevant enzyme-catalyzed reaction with a root mean square error of prediction (RMSEP) of 0.04 pH levels.

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