The Application of Dielectric Spectroscopy and Biocalorimetry for the Monitoring of Biomass in Immobilized Mammalian Cell Cultures
Open Access
Abstract
The purpose of this study was to introduce dielectric spectroscopy and biocalorimetry as monitoring methods to follow immobilised Chinese Hamster Ovary (CHO) cell culture development. The theory behind both monitoring techniques is explained and perfusion cultures are performed in a Reaction Calorimeter (eRC1 from Mettler Toledo) as an application example. The findings of this work show that dielectric spectroscopy gives highly reliable information upon the viable cell density throughout the entire culture. On the other hand, the RC1 could only provide accurate data from day 5, when the cell density exceeded 4 × 106 vcells∙mL−1 (viable cell per mL) working volume (WV). The method validation showed the limit of detection (LOD) for 1.4 L cultures to be 8.86 × 106 vcells∙mL−1, a viable cell density commonly achieved in fed-batch and the early stages of a perfusion culture. This work suggests that biocalorimetry should be possible to implement at industrial scale to monitor CHO cell cultures.Keywords
Funding Information
- Science Foundation Ireland (08/IN.1/B1948)
This publication has 39 references indexed in Scilit:
- Mammalian cell protein expression for biopharmaceutical productionBiotechnology Advances, 2012
- Bioprocess engineering aspects of heterologous protein production in Pichia pastoris: A reviewBiochemical Engineering Journal, 2012
- Enhanced Production of Human Recombinant Proteins from CHO cells Grown to High Densities in Macroporous MicrocarriersMolecular Biotechnology, 2011
- Biomass measurement online: the performance of in situ measurements and software sensorsJournal of Industrial Microbiology and Biotechnology, 2008
- CHO immobilization in alginate/poly-l-lysine microcapsules: an understanding of potential and limitationsCytotechnology, 2007
- On-line Measurements and Control of Viable Cell Density in Cell Culture Manufacturing Processes using Radio-frequency ImpedanceCytotechnology, 2006
- Production of recombinant protein therapeutics in cultivated mammalian cellsNature Biotechnology, 2004
- On‐line biomass monitoring of CHO perfusion culture with scanning dielectric spectroscopyBiotechnology and Bioengineering, 2003
- The dielectric properties of biological cells at radiofrequencies: applications in biotechnologyEnzyme and Microbial Technology, 1999
- On the dielectric properties of cell suspensions at high volume fractionsJournal of Electroanalytical Chemistry, 1992