Biomass sensors for biopharmaceutical manufacturing

1. Zhang, A et al, 2015; Advanced process monitoring and feedback control to enhance cell culture process production and robustness, Biotechnology and Bioengineering

Explores and establishes a capacitance based automated feed strategy for complex nutrients.

Proves that a capacitance based feed strategy is better than a fixed volume feed strategy. When process variations are introduced, the capacitance based strategy outperformed the fixed volume feed strategy and was comparable to the ‘golden’ batch where no process variations were introduced.

This is primarily because Aber capacitance measurements are in real time and the strategy adjusts feed amount automatically, based on the growth of cells.

2. Fernandes, J. et al., 2018; Development of capacitance tools: At-line method for assessing biomass of mammalian cell culture and fixed cell calibration standard, Biotech

Presents a capacitance based control strategy independent of any offline reference method.

This is achieved by establishing a 4-tier capacitance measurement strategy
– Probe A in vessel – controlling the process
– Probe B in vessel – monitoring probe A’s performance
– Probe C – At line used for troubleshooting deviation
– Historical capacitance data

Presents a robust troubleshooting example in 15000 L manufacturing scale based on this strategy – where inline and historical capacitance deviation prompted an investigation, which resulted in the finding of an accidental omission of a critical raw material in the medium.

3. Moore, B. et al., 2019; Case study: The characterization and implementation of dielectric spectroscopy (biocapacitance) for process control in a commercial GMP CHO manufacturing process, Biotech Prog

Proves that Aber capacitance can be used across different scales, from 5L to 15,000L (R² = 0.990).

Explores a strategy where feeding with Aber capacitance every 4 h instead of 24h resulted in an increased titer of 21%, prevention of glutamate depletion in culture and improved cell growth.

Presents the predictive capacitance based feed strategy for glucose, which outperformed a fixed volume feed based strategy and performed comparably with Raman. Aber capacitance requires less resource investment and is easier to use than Raman.

4. Ma, F. et al., 2019; Real-time monitoring and control of CHO cell apoptosis by in situ multifrequency scanning dielectric spectroscopy, Process Biochem

Applied frequency scanning using the Aber probe to detect apoptosis sooner in culture.

Furthermore, capacitance based probes were used in a strategy to reverse apoptosis in culture due to earlier sensitivity to cell death. This was not possible with the offline trypan blue measurement.