Additionally, the transition from off-line discrete sampling to continuous in-line measurement enables the development of automated calculation and process control strategies not possible with off-line sampling only. Notably, a continuous permittivity-derived VCD measurement can be harnessed to improve the resolution and quantity of data input into the trapezoid calculation, providing a robust IVCC calculation. 2 The accuracy and usefulness of the IVCC calculation can be dramatically improved by replacing periodic off-line sampling with a continuous measurement of viable cell concentration using in-line permittivity measurement. Large gaps between off-line samples, the inherent non-linearity of cell growth, and measurement error present in off-line sampling techniques all contribute to the limited predictive capacity that IVCC calculations based on off-line VCD can provide. The accuracy and realistic representation of the trapezoid calculation on the culture is highly dependent upon the linearity of the culture growth between samples and the frequency of measurements. Traditionally, a numerical approximation of IVCC is determined using the trapezoid approximation between two off-line VCD data points (Figure 1). Of bolus addition needed to return to a specific concentration set-point. To directly assess change of nutrient profiles in-culture and subsequently determine the concentration and volume 1 Specifically, calculated change in IVCC can be used In fed-batch processes the IVCC term becomes highly important for not only characterizing culture progression, butĭetermining process action with regards to bolus feed additions. IVCC calculated for a specific culture timeframe can be combined with product titers to assess culture productivity trends within specified timeframes of the process or can be used to estimate nutrient consumption profiles based upon cell-specific nutrient requirements for a process. IVCC quantifies the effective working time for a dynamic viable cell concentration within a given frame of time, analogous to the calculation of man-hours. The Integral (area under the curve) of Viable Cell Density (IVCD) or Concentration (IVCC) is an essential calculated metric in cell culture operations. Knowledge Base (Articles, FAQs, Downloads).
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