Estimation of Viable Cell Density During Late Growth Phase of CHO Cell Culture Using Dielectric Spectroscopy

In mammalian cell culture processes, viable cell density (VCD) is one of the most crucial parameters in monitoring the current status of the cell growth and protein production. Among the various real-time monitoring tools for the VCD in CHO cell culture, dielectric spectroscopy is one of the most reliable tools due to its simplicity, robustness and accuracy, thus enabling efficient monitoring and control of the corresponding processes. However, one of the critical drawbacks of the dielectric spectroscopy is the frequent deteriorations of its accuracy during the late-growth phases of CHO cell culture due to the abrupt changes in the cell physiology as well as their environmental conditions. Therefore, in this study, various kinds of chemometrics tools were employed to understand the spectral dynamics of the dielectric spectroscopy over the entire period of CHO cell culture consisting of different cell growth phases. Then, using the dielectric spectra measured from several batches of the bioreactor operations, the performance of different multivariate regression models was compared to the conventional Cole-Cole equation-based approaches in estimating the VCD in CHO cell culture. The results obtained from this study illustrated the usefulness of the multivariate regression tools in compensating the spectral dynamics observed during the different cell growth phases, inherently into the given estimation models, and the robust prediction performance from the dielectric spectroscopy can be realized by using the regression model based on locally-weighted partial least squares (LWPLS), allowing the optimal and stable estimation of the VCD during CHO cell culture, regardless of the differences in the cell growth phases.