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Sensors 2018, 18(3), 900; https://doi.org/10.3390/s18030900

Dielectric Spectroscopy and Optical Density Measurement for the Online Monitoring and Control of Recombinant Protein Production in Stably Transformed Drosophila melanogaster S2 Cells

1
Institute of Bioprocess Engineering and Pharmaceutical Technology, University of Applied Sciences Mittelhessen, Wiesenstrasse 14, 35390 Giessen, Germany
2
Mathematical Institute, Justus-Liebig University of Giessen, Arndtstrasse 2, 35392 Giessen, Germany
3
Department of Chemical Engineering, Kansas State University, 1005 Durland Hall, Manhattan, KS 66506, USA
4
Faculty of Biology and Chemistry, Justus Liebig University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany
5
Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Bioresources Project Group, Winchesterstrasse 2, 35394 Giessen, Germany
*
Author to whom correspondence should be addressed.
Received: 23 February 2018 / Revised: 14 March 2018 / Accepted: 15 March 2018 / Published: 18 March 2018
(This article belongs to the Special Issue Sensors for Cell Analysis)
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Abstract

The production of recombinant proteins in bioreactors requires real-time process monitoring and control to increase process efficiency and to meet the requirements for a comprehensive audit trail. The combination of optical near-infrared turbidity sensors and dielectric spectroscopy provides diverse system information because different measurement principles are exploited. We used this combination of techniques to monitor and control the growth and protein production of stably transformed Drosophila melanogaster S2 cells expressing antimicrobial proteins. The in situ monitoring system was suitable in batch, fed-batch and perfusion modes, and was particularly useful for the online determination of cell concentration, specific growth rate (µ) and cell viability. These data were used to pinpoint the optimal timing of the key transitional events (induction and harvest) during batch and fed-batch cultivation, achieving a total protein yield of ~25 mg at the 1-L scale. During cultivation in perfusion mode, the OD880 signal was used to control the bleed line in order to maintain a constant cell concentration of 5 × 107 cells/mL, thus establishing a turbidostat/permittistat culture. With this setup, a five-fold increase in productivity was achieved and 130 mg of protein was recovered after 2 days of induced perfusion. Our results demonstrate that both sensors are suitable for advanced monitoring and integration into online control strategies. View Full-Text
Keywords: dielectric spectroscopy; impedance spectroscopy; optical density measurements; process monitoring; process control; fermentation; recombinant protein production; Drosophila S2 dielectric spectroscopy; impedance spectroscopy; optical density measurements; process monitoring; process control; fermentation; recombinant protein production; Drosophila S2
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Zitzmann, J.; Weidner, T.; Eichner, G.; Salzig, D.; Czermak, P. Dielectric Spectroscopy and Optical Density Measurement for the Online Monitoring and Control of Recombinant Protein Production in Stably Transformed Drosophila melanogaster S2 Cells. Sensors 2018, 18, 900.

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