Insights into monitoring changes in the viable cell density and cell physiology using scanning, multi-frequency dielectric spectroscopy

Carvell, John; Graham, Lisa; Downey, Brandon

doi:10.1186/1753-6561-7-s6-p4

Cited by 2 publications

(4 citation statements)

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“…Offline measurements of VCD are presented alongside to illustrate accuracy of prediction. The VCD values estimated by both two Cole‐Cole equation based approaches were in good agreement with the off‐line measurements during the exponential growth phase, which is in line with the previous studies . However, after the CHO cells reached the stationary phase, both approaches failed to provide a reliable prediction of VCD.…”

Section: Resultssupporting

confidence: 89%

“…(A)). Similarly, in the full Cole‐Cole approach, the calculated values of the VCD and cell radius in Equations could not be matched to the true values of the off‐line measurements during the late‐growth phases, primarily for the same reasons . Therefore, a theoretical Cole‐Cole equation based approach cannot adequately accommodate the complex dynamics associated with the different cell growth phases.…”

Section: Resultsmentioning

confidence: 99%

“…The VCD values estimated by both two Cole-Cole equation based approaches were in good agreement with the off-line measurements during the exponential growth phase, which is in line with the previous studies. 32,39,56 However, after the CHO cells reached the stationary phase, both approaches failed to provide a reliable prediction of VCD. Cells in culture generally experience drastic changes in their physiological and metabolic states during the late-growth phase as media is spent and waste product accumulate; this seems to, cause subsequent changes in the spectral dynamics.…”

Section: Estimation Of Vcd Using Cole-cole Equationmentioning

confidence: 99%

“…Similarly, in the full Cole-Cole approach, the calculated values of the VCD and cell radius in Equations (2)-(4) could wileyonlinelibrary.com/jctb (11) not be matched to the true values of the off-line measurements during the late-growth phases, primarily for the same reasons. 39,56 Therefore, a theoretical Cole-Cole equation based approach cannot adequately accommodate the complex dynamics associated with the different cell growth phases. One possible remedy might be to periodically measure some of the parameters included in Equations (2)-(4) of the course of the culture, for example cell radius.…”

Section: Estimation Of Vcd Using Cole-cole Equationmentioning

confidence: 99%

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Dielectric spectroscopy‐based estimation ofVCDinCHOcell culture

Lee

Carvell

Brorson

et al. 2014

J of Chemical Tech & Biotech

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BACKGROUND In mammalian cell culture processes, viable cell density (VCD) is one of the most crucial parameters for monitoring of the current status of cell growth and protein production. Among the various real‐time monitoring tools available for VCD in Chinese hamster ovary (CHO) cell culture, dielectric spectroscopy is one of the more reliable due to its simplicity, robustness and accuracy. These attributes enable efficient monitoring and control of the corresponding processes. However, one of the major drawbacks of dielectric spectroscopy is frequent deterioration of accuracy during the late‐growth phase of CHO cell culture. This can be caused by abrupt changes in the cell physiology, as well as environmental conditions. RESULTS In this study, various kinds of chemometric tools were employed to understand the spectral dynamics of dielectric spectroscopy during extended CHO cell culture, including different cell growth phases. Then, the performance of different multivariate regression models were compared with conventional Cole‐Cole equation‐based approaches. The models were compared in their ability to estimate VCD in CHO cell culture from dielectric spectra from several batches of bioreactor operations. Multivariate analysis of dielectric spectral datasets clearly revealed the time‐varying evolution of spectral dynamics during the transition between cell growth phases. The best prediction performance from the dielectric spectroscopy was realized using a regression model based on locally‐weighted partial least squares (LWPLS). This estimation model best compensated for spectral dynamics observed during the different cell growth phases. CONCLUSION Dielectric spectroscopy combined with LWPLS allows achievement of optimal and stable estimation of VCD during CHO cell culture, regardless of inherent differences in cell growth phases. © 2014 Society of Chemical Industry

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Estimation Of Vcd Using Cole-cole Equationmentioning

confidence: 99%

Section: Estimation Of Vcd Using Cole-cole Equationmentioning

confidence: 99%

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Dielectric spectroscopy‐based estimation ofVCDinCHOcell culture

Lee

Carvell

Brorson

et al. 2014

J of Chemical Tech & Biotech

Self Cite

View full text Add to dashboard Cite

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Trends in Process Analytical Technology: Present State in Bioprocessing

Jenzsch

Bell

Buziol

et al. 2017

Advances in Biochemical Engineering/Biotechnology

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Process analytical technology (PAT), the regulatory initiative for incorporating quality in pharmaceutical manufacturing, is an area of intense research and interest. If PAT is effectively applied to bioprocesses, this can increase process understanding and control, and mitigate the risk from substandard drug products to both manufacturer and patient. To optimize the benefits of PAT, the entire PAT framework must be considered and each elements of PAT must be carefully selected, including sensor and analytical technology, data analysis techniques, control strategies and algorithms, and process optimization routines. This chapter discusses the current state of PAT in the biopharmaceutical industry, including several case studies demonstrating the degree of maturity of various PAT tools. Graphical Abstract Hierarchy of QbD components.

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Insights into monitoring changes in the viable cell density and cell physiology using scanning, multi-frequency dielectric spectroscopy

Cited by 2 publications

References 4 publications

Dielectric spectroscopy‐based estimation ofVCDinCHOcell culture

Dielectric spectroscopy‐based estimation ofVCDinCHOcell culture

Trends in Process Analytical Technology: Present State in Bioprocessing

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