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Sensors 2015, 15(9), 22128-22150; doi:10.3390/s150922128

Universal Capacitance Model for Real-Time Biomass in Cell Culture

1
Institute of Chemical Engineering, Division of Biochemical Engineering, Vienna University of Technology, Gumpendorfer Strasse 1A 166-4, 1060 Vienna, Austria
2
Boehringer Ingelheim Pharma GmbH & Co. KG Department Bioprocess Development, 88400 Biberach, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Alexander Star
Received: 17 April 2015 / Revised: 18 July 2015 / Accepted: 25 August 2015 / Published: 2 September 2015
(This article belongs to the Special Issue Sensors for Bioprocess Monitoring and Control)
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Abstract

Capacitance probes have the potential to revolutionize bioprocess control due to their safe and robust use and ability to detect even the smallest capacitors in the form of biological cells. Several techniques have evolved to model biomass statistically, however, there are problems with model transfer between cell lines and process conditions. Errors of transferred models in the declining phase of the culture range for linear models around +100% or worse, causing unnecessary delays with test runs during bioprocess development. The goal of this work was to develop one single universal model which can be adapted by considering a potentially mechanistic factor to estimate biomass in yet untested clones and scales. The novelty of this work is a methodology to select sensitive frequencies to build a statistical model which can be shared among fermentations with an error between 9% and 38% (mean error around 20%) for the whole process, including the declining phase. A simple linear factor was found to be responsible for the transferability of biomass models between cell lines, indicating a link to their phenotype or physiology. View Full-Text
Keywords: CHO cell culture; capacitance; fed batch; PLS; statistical model CHO cell culture; capacitance; fed batch; PLS; statistical model
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Konakovsky, V.; Yagtu, A.C.; Clemens, C.; Müller, M.M.; Berger, M.; Schlatter, S.; Herwig, C. Universal Capacitance Model for Real-Time Biomass in Cell Culture. Sensors 2015, 15, 22128-22150.

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