Impact of microcarrier coverage on using permittivity for on-line monitoring high adherent Vero cell densities in perfusion bioreactors

The paper presents the interest of on-line permittivity monitoring to estimate the density of Vero cells growing on microcarriers (MCs), even when high cell densities were reached in perfusion bioreactors (4.5 × 106 cells ml−1). Cultures were performed with various MCs concentrations in a reactor equipped with a settling tube. A linear correlation between on-line permittivity and off-line volumetric cell concentration was observed provided that MCs are not fully covered by cells. High permittivities such as 250 pF cm−1 could be measured without signal saturation of the Fogale Biomass system®. The correlation was no longer linear when cell density per carrier exceeded 100% cell confluency corresponding to 150 cells MC−1 (0.15 × 106 cells cm−2). This behaviour was attributed to the decrease of cell volume when cells saturated MCs surface. It mainly happened when low MCs concentration and continuous medium renewing were used. Therefore, permittivity sensor can be considered as a reliable tool to monitor on-line adherent cell densities not exceeding total cell confluency. Moreover, it could be useful to detect when cell confluency occurs.

► High adherent cell density in perfused reactor can be followed by on-line permittivity.
► Low carrier level induces cell confluency and loss of correlation linearity.
► Measurement of cell diameter by image analysis allows total biovolume calculation.
► The decrease of cell size from the time of confluency induces lower permittivity.
► On-line permittivity detects the time of complete coverage of microcarriers.