In-line Measurement of Viable Cell Density in a Photobioreactor
- Industry: Biopharma Production
- Application field: Control of Filamentous Moss Culture
- Hamilton products: Incyte and ArcView Controller
Innovative Bioprocesses for Therapeutic Protein Production
In all production processes (traditional mammalian and more innovative moss-based), growth rate and production rate are key evaluation parameters of culture performance. Many factors, such as light and nutrition, can influence the performance of the moss culture. Therefore, a fast and reliable measurement of viable cell density is necessary for process optimization and, at a later stage, to guarantee stable and robust production. Off-line measurements are too time-consuming and do not accurately reflect the moss cell density in the bioreactor. Moss cultures grow in filaments, causing aggregation. Without distinct individual cells, an accurate correlation between the off-line measurement and in-situ signal may be difficult to accomplish. Real-time monitoring offers the option for constant control strategies, as enforced by Process Analytical Technology (PAT) from the US Food & Drug Administration (FDA).
The in-line cell density (permittivity) signals were compared with the off-line cell dry weight in g/L. Permittivity was also compared to other process parameters, such as concentration of important nutrients, pH, and light intensity for process optimization.
Benefits of Incyte
- Accurate in-line growth determination in moss cultures over longer process time
- Reliable measurement of filamentous moss cultures' growth
- Easy installation and usage
In-line VCD Monitoring Performances
The values of in-line viable cell density and off-line total cell density obtained for the bioreactor set-up are shown in Figure 2. The in-line monitoring of Incyte shows a good comparability to the off-line method. Deviations are assumed to be due to the total biomass determination in the off-line measurement in contrast to the viable cell determination in the in-line measurement. Further runs should be performed for a determination of the measurement methods. The signal showed high stability all along the bioprocess. Integration into the process control system is planned for automated regulation of harvesting and continuous processing. These results show that permittivity sensors can successfully be used for real-time monitoring of filamentous moss viable cell density.
Figure 2: In-line permittivity versus off-line cell density. The green line represents the Incyte in-line measurement. The orange dots represent the total cell count with the reference off-line method.