Continuous Online Measurement of Viable Cell Density for Improved Process Insight

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Trials Prove Positive Qualities

The advantages of Incyte have been verified by numerous trials and experiments performed, not only by Hamilton, but by customers and independent researchers. A comparative off-line/on-line test with CHO cells was conducted at a university. To this end, the cell factor for each cell type was determined, thus determining the correlation between the measured permittivity and the off-line cell concentration — done by counting and dyeing the viable cells in a manual procedure. Figure 1 (see picture gallery) shows the linear correlation.

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In Figure 2 the permittivity measurement shows consistent cell density values during the growth phase and provides a good correlation with different offline methods. The CHO cells’ growth phase showed matching values in the batch process. The cell density increased after a certain period and the nutrients decreased at the same time — showing deviating and less precise values in the off-line measurement compared to Incyte.

The growth curve in figure 3 shows that each nutrient feed lead to a dilution effect. The experiment was repeated in a fed-batch-process. Every 48 hours, commencing 72 hours after the culture start, 15 percent of the volume was added with each feeding. The permittivity dropped shortly.

Researchers especially positively mention this property and the direct documentation of the results. With the increasing duration of the cultivation, the number of cell fragments and dead cells grew, without affecting Incyte. The longer the process was performed, the more the off-line and on-line values differed, as the off-line method needed more attention and the samples had to be evaluated in a timely manner in the laboratory.

Recognizing Critical Situations Immediately

The real-time measurement of viable cell density with Incyte is not only suitable for CHO cells. Incyte’s measurement results have also been proven with Baby Hamster Kidney cells (BHK), insect cells, yeast, bacteria such as E.coli, and filamentous fungi. With each application, the sensor provides analysis possibilities and information concerning critical situations, which may have been missed with the off-line method. Monitoring the viable cell density delivers important findings, since changes are immediately detected, allowing the next steps to conduct right away. With on-line viable cell density information, cultivation conditions can be optimized, increasing yield with important information regarding the cell physiology.

Portfolio for Relevant Process Parameters

Hamilton does not only offer sensors for viable cell density monitoring, but equally pH value, dissolved oxygen concentration (optical, or amperometric) and conductivity. All sensors are available as analog version with transmitter or as the highly innovative Arc technology. Arc sensors have integrated transmitters and provide a compensated, digital signal. The offer of all these parameters makes Hamilton your reliable and unique supplier.

Meet the Hamilton experts and learn more about the Incyte sensors at Achema 2018: Hall 11.1, Stand F43

* The author is Marketing Communication Manager at Hamilton Bonaduz AG, Bonaduz/Switzerland.

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