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Bioprocessing

Continuous Online Measurement of Viable Cell Density for Improved Process Insight

| Author / Editor: Volker Kupitz / Dr. Jörg Kempf

Breaking new ground in bioprocessing: Viable cells behave like little capacitors. In an alternating electrical field their polarization and depolarization can be measured and the signal can be correlated to the bio-volume, resp. the viable cell density. Because only viable cells can be polarized, this method is insensitive to cell debris as well as to microcarriers.
Breaking new ground in bioprocessing: Viable cells behave like little capacitors. In an alternating electrical field their polarization and depolarization can be measured and the signal can be correlated to the bio-volume, resp. the viable cell density. Because only viable cells can be polarized, this method is insensitive to cell debris as well as to microcarriers. (Source: ©Paulista; ©gonin - stock.adobe.com; Hamilton [M]GötzelHorn)

Online measurement with methods such as control of pH and dissolved oxygen are common for most biological processes. In fact, many parameters can be monitored but those directly related to cell physiology are time-consuming offline measurements that only provide a reactionary window into the past. Learn how to increase yield and decrease effort with innovative sensors.

Biological processes are rapidly gaining importance in the pharmaceutical industry due to the utility of vaccines, antibodies, and other pharmaceuticals. Since the cell physiology is very sensitive, bioprocesses require regular monitoring and control for a constant environment to ensure optimal growth and high productivity. CHO cells (Chinese Hamster Ovary) serve as a common example. They are used in bio-pharma for industrial production of monoclonal antibodies (among others) that are used for therapy and diagnosis purposes. Negative effects on the cells, and consequently on the productivity, must be avoided since the costs for mammalian cell cultivation is very high.

Contamination and falsely interpreting data are some of the most detrimental mistakes in bioprocessing, while nutrient deficiency, accumulation of apoptotic cells, unintended change in the pH value, or genetics can cause significant problems as well.

In order to attain an economical production process, the most important parameters, such as the viable cell density, need to be measured.

Off-line Measurements Involve Risks

Measurements of viable cell density are commonly conducted via off-line methods, in which samples are taken from the bioreactors and analysed cumbersomely. The procedure involves several risks:

  • Sampling is a time-consuming process with high risk of batch contamination.
  • In addition, the measurements vary and qualified personnel needs to be available.

On-line determination of viable cell density is the safe and accurate way of the future — minimizing risks in this way. The method is not only linked to far lower risks but delivers more precise results, as well as real-time data, for more refined analysis and decisions. The Incyte Sensor of Hamilton Bonaduz is designed for exactly this purpose.

Increasing Yield and Decreasing Effort

The Incyte, a Viable Cell Density Sensor, was developed for mammalian cell, yeast, and bacterial fermentation applications. A decisive advantage is that microcarriers, dead cells and cell debris do not affect the measurement, as the operating principle of the viable cell density measurement is based on permittivity: viable cells act like small capacitors in an alternating electronic field. Their charge and hence their permittivity are determined with the sensor. Yield improvement, less work effort and therefore lower costs are further assets of the technology as well as the immediate detection of the cell’s physiology changes. Incyte provides precise information to determine of process changes in-time.

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