Systementwicklung für die impedanzspektroskopische Erfassung der Zellzahl und -viabilität in 2D- und 3D-Kulturvon Grit Blume
In this work methods and tools for non-destructive online measurement of cell growth and cell viability in different cultivation systems were developed. For this purpose impedance sensors on polymer foils were developed using microsystems technology. The use of microsystems technology makes it possible to adapt the foils to different geometry and applications. The aim is the production of foils and foldable foil laminates that enable the generation of 2D and 3D growth surfaces for cell culture. The polymer production processes were modified so that non-cytotoxic foils (respecting DIN EN ISO 10993-5:2010) could be produced. Different analytical techniques were used to identify key parameters for the production of non-cytotoxic foils. Protocols for the manufacturing of non-cytotoxic SU-8 100 foils, polyimide foils, laminates of these two and polymer sensor foils were established. Methods for online measurement of cell growth and cell viability were developed. The different growth phases were identified by impedance spectroscopy and the beta dispersion (as measure for cell viability) was recorded. Criteria for determination of cell growth and viability were established. Different perfusion bioreactors that can be equipped with the foil sensors were designed, manufactured and evaluated. A scaffold design based on the developed polymer processes was proposed. This scaffold, equipped with sensors, can be integrated in the manufactured 3D perfusion reactor. Hence methods and tools for non-destructive online measurement of cell growth and cell viability in different cultivation systems were developed.