title: Universal Capacitance Model for Real-Time Biomass in Cell Culture.
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.
authors.affiliation: Institute of Chemical Engineering, Division of Biochemical Engineering, Vienna University of Technology, Gumpendorfer Strasse 1A 166-4, 1060 Vienna, Austria. vkonakovtuwien@gmail.com.
authors.forename: Viktor
authors.initials: V
authors.lastname: Konakovsky
authors.affiliation: Institute of Chemical Engineering, Division of Biochemical Engineering, Vienna University of Technology, Gumpendorfer Strasse 1A 166-4, 1060 Vienna, Austria. civan.yagtu.tuwien@gmail.com.
authors.forename: Ali Civan
authors.initials: AC
authors.lastname: Yagtu
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG Department Bioprocess Development, 88400 Biberach, Germany. christoph.clemens@boehringer-ingelheim.com.
authors.forename: Christoph
authors.initials: C
authors.lastname: Clemens
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG Department Bioprocess Development, 88400 Biberach, Germany. markus_michael.mueller@boehringer-ingelheim.com.
authors.forename: Markus Michael
authors.initials: MM
authors.lastname: Müller
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG Department Bioprocess Development, 88400 Biberach, Germany. martina.berger@boehringer-ingelheim.com.
authors.forename: Martina
authors.initials: M
authors.lastname: Berger
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG Department Bioprocess Development, 88400 Biberach, Germany. stefan.schlatter@boehringer-ingelheim.com.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schlatter
authors.affiliation: Institute of Chemical Engineering, Division of Biochemical Engineering, Vienna University of Technology, Gumpendorfer Strasse 1A 166-4, 1060 Vienna, Austria. christoph.herwig@tuwien.ac.at.
authors.forename: Christoph
authors.initials: C
authors.lastname: Herwig
mesh_terms: D000818:Animals; D018533:Biomass; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D025802:Electric Capacitance; D008954:Models, Biological; D015233:Models, Statistical
keywords: CHO cell culture; PLS; capacitance; fed batch; statistical model