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- Title
A novel real-time method to estimate volumetric mass biodensity based on the combination of dielectric spectroscopy and soft-sensors.
- Authors
Ehgartner, Daniela; Sagmeister, Patrick; Herwig, Christoph; Wechselberger, Patrick
- Abstract
BACKGROUND The PAT initiative encourages designing, analyzing, and controlling manufacturing through timely measurements. Dielectric measurements and first principle soft-sensors emerged as valuable real-time bioprocess analytical PAT tools to improve process understanding and control capabilities. RESULTS The estimation of a novel physiological variable, bio-density is presented, using a combination of two PAT sensors, dielectric spectroscopy and a soft-sensor based on first principle elemental balances. Within this contribution, calibrations for the estimation of biomass dry weight using dielectric measurements were found to change in the transition from batch- to fed-batch and within the induction phase for two recombinant E. coli bioprocesses. This was explained by a change in cell size, as indicated by flow cytometric measurements, light microscopy and changes in the beta dispersion dielectric spectrum. Biomass dry weight was accurately determined using a first principle soft-sensor. The combination of both signals allowed the real-time estimation of a new physiological variable, interpreted as bio-density. Applying this concept, batch/fed-batch and induction phase physiological changes were successfully observed in real time. Furthermore, a correlation with the specific product titer was observed. CONCLUSION This contribution enhances the application spectrum of dielectric measurements and soft-sensors for the detection of physiological changes and recombinant product estimation, aiming at more efficient design, monitoring and control of bioprocesses as demanded by the process analytical technology ( PAT) initiative. © 2014 Society of Chemical Industry
- Subjects
DIELECTRIC measurements; PRINCIPAL components analysis; CELL morphology; BROADBAND dielectric spectroscopy; BIOTECHNOLOGICAL process monitoring; ESCHERICHIA coli
- Publication
Journal of Chemical Technology & Biotechnology, 2015, Vol 90, Issue 2, p262
- ISSN
0268-2575
- Publication type
Article
- DOI
10.1002/jctb.4469