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Soft sensor based on 2D-fluorescence and process data enabling real-time estimation of biomass in Escherichia coli cultivations.


ABSTRACT: In bioprocesses, specific process responses such as the biomass cannot typically be measured directly on-line, since analytical sampling is associated with unavoidable time delays. Accessing those responses in real-time is essential for Quality by Design and process analytical technology concepts. Soft sensors overcome these limitations by indirectly measuring the variables of interest using a previously derived model and actual process data in real time. In this study, a biomass soft sensor based on 2D-fluorescence data and process data, was developed for a comprehensive study with a 20-L experimental design, for Escherichia coli fed-batch cultivations. A multivariate adaptive regression splines algorithm was applied to 2D-fluorescence spectra and process data, to estimate the biomass concentration at any time during the process. Prediction errors of 4.9% (0.99 g/L) for validation and 3.8% (0.69 g/L) for new data (external validation), were obtained. Using principal component and parallel factor analyses on the 2D-fluorescence data, two potential chemical compounds were identified and directly linked to cell metabolism. The same wavelength pairs were also important predictors for the regression-model performance. Overall, the proposed soft sensor is a valuable tool for monitoring the process performance on-line, enabling Quality by Design.

SUBMITTER: Bayer B 

PROVIDER: S-EPMC6999058 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Soft sensor based on 2D-fluorescence and process data enabling real-time estimation of biomass in <i>Escherichia coli</i> cultivations.

Bayer Benjamin B   von Stosch Moritz M   Melcher Michael M   Duerkop Mark M   Striedner Gerald G  

Engineering in life sciences 20191111 1-2


In bioprocesses, specific process responses such as the biomass cannot typically be measured directly on-line, since analytical sampling is associated with unavoidable time delays. Accessing those responses in real-time is essential for Quality by Design and process analytical technology concepts. Soft sensors overcome these limitations by indirectly measuring the variables of interest using a previously derived model and actual process data in real time. In this study, a biomass soft sensor bas  ...[more]

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