University of Oulu

T. Reinecke, P. Biechele, M. Sobocinski, H. Suhr, K. Bakes, D. Solle, H. Jantunen, T. Scheper, S. Zimmermann, Continuous noninvasive monitoring of cell growth in disposable bioreactors, Sensors and Actuators B: Chemical, Volume 251, 2017, Pages 1009-1017, ISSN 0925-4005,

Continuous noninvasive monitoring of cell growth in disposable bioreactors

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Author: Reinecke, T.1; Biechele, P.2; Sobocinski, M.3;
Organizations: 1Institute of Electrical Engineering and Measurement Technology, Dept. of Sensors and Measurement Technology, Leibniz Universität Hannover, Appelstr. 9A, 30167 Hannover, Germany
2Institute of Technical Chemistry, Leibniz Universität Hannover, Callinstr. 5, 30167 Hannover, Germany
3Microelectronics Research Unit, University of Oulu, Erkki Koiso-Kanttilan Katu 3, 90570 Oulu, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
Persistent link:
Language: English
Published: Elsevier, 2017
Publish Date: 2019-11-30


To ensure high quality output of biotechnological processes, relevant process parameters need to be monitored. As bioprocesses are increasingly executed in single use bioreactors, there is an increasing demand for new sensors applicable to these processes. In this work, we investigate different approaches for continuous non-invasive cell growth monitoring, especially for single use bioreactor applications. Therefore, the permittivity of the cell culture is used as a measure for the biomass. In a first step, a measuring procedure based on the transmission measurement of an electromagnetic wave is investigated. It appears that the penetration depth of this sensor is not sufficient for a noninvasive measurement through the polymer wall of a single use bioreactor. Therefore, alternative setups based on magnetic induction are investigated. The initial setup is very simple. It consists of a planar coil connected to an impedance analyzer. The coil is attached to the outside of the polymer foil of the single use bioreactor and an impedance spectrum is measured. To evaluate the sensor, E. coli cultivations are performed in a modified cultivation setup, which enables measurements through the polymer foil of a Sartorius BIOSTAT® CultiBag RM, and additionally allows sampling of culture medium for optical density reference measurements. The resonance peak of the coil in the impedance spectrum, is observed as measure for the optical density. Regardless of the simple sensor construction, we found a good correlation between optical density and the damping ratio of the resonance peak. However, the sensor signal shows saturation towards high optical densities. Therefore, an LTCC coil producing a higher magnetic flux density in the culture medium is investigated subsequently. This sensor shows a linear response up to high optical densities, but the sensitivity is reduced compared to the former used coil and therefore scattering of the data is increased. However, to increase the sensitivity, a linear variable differential transformer is realized. Using this setup, the influence of the primary magnetic flux is eliminated from the measuring voltage. This approach delivers the most promising results, as the sensor response is linear up to high optical densities and data scattering is low.

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Series: Sensors and actuators. B, Chemical
ISSN: 0925-4005
ISSN-E: 1873-3077
ISSN-L: 0925-4005
Volume: 251
Pages: 1009 - 1017
DOI: 10.1016/j.snb.2017.05.111
Type of Publication: A1 Journal article – refereed
Field of Science: 220 Industrial biotechnology
Copyright information: © 2017 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license