At-Bioreactor Trace Metal Quantification and Statistical Process Control in CHO Cell-culture Production

The goals of this project are 1) to develop an offline assay for trace metal quantification and 2) to develop an at-reactor trace metal quantification instrument towards improved monitoring and control of critical trace metals in cell-culture production.

Industry Need

While great improvements have been attained in productivity, challenges remain for achieving consistent product quality from CHO culture systems. Trace metals have been shown to have a significant impact on product quality.

Approach

This collaborative project serves to provide the why’s and how’s in terms of the use of metals content as a process control element in CHO cell-based mAb production.

Impacts

At line measurement of trace metals in near real time to enable process consistency and control

Outputs/Deliverables

Development of offline assay for trace-metal quantification
Deliverable 2: LS-APGD ionization source and mass spectrometer for at-reactor metals quantification

Publications

At-Bioreactor Trace Metal Quantification and Statistical Process Control in CHO Cell-culture Production (PC1.0-015), NIIMBL Member Forum, Virtual, September 24, 2020.

Graham, R. J., Bhatia, H., & Yoon, S. (2019). Consequences of trace metal variability and supplementation on Chinese hamster ovary (CHO) cell culture performance: A review of key mechanisms and considerations. Biotechnology and Bioengineering, 116(12), 3446-3456. https://doi.org/10.1002/bit.27140

Hall, K., Polanco, A., Liang, G., Graham, R., Galbraith, S., Yoon, S., & Marcus, K., Utilizing the Liquid Sampling – Atmospheric Pressure Glow Discharge for At-Bioreactor Quantification of Trace Metals in Cell Culture Media via Mass Spectrometry, 2020 Winter Conference on Plasma Spectrochemistry, Tucson, AZ, January 13, 2020.

Marcus, K., & Yoon, S., Trace Metal Quantification, NIIMBL Annual Meeting, Washington, DC, July 10, 2019.

Marcus, K., Goals, Motivations, and Happenstance: The Development of the Liquid Sampling-Atmospheric Pressure Glow Discharge (LS-APGD) Microplasma for Diverse Applications, 2019 Pittsburgh Conference and Exhibition, Philadelphia, PA, March 17, 2019.

Marcus, K., Hall, K., Williams, T., Bills, J., Paing, H., Hoegg, E., & Koppenaal, D., The Liquid Sampling-Atmospheric Pressure Glow Discharge: A Combined Atomic and Molecular (CAM) Ionization Source, 2020 Conference on Plasma Spectrochemistry, Tucson, AZ, January 15, 2020.

Polanco, A., Liang, G., Park, S., Wang, Y., Graham, R. J., & Yoon, S. (2023). Trace metal optimization in CHO cell culture through statistical design of experiments. Biotechnology Progress, 39(6). https://doi.org/10.1002/btpr.3368.

Williams, T. J., & Marcus, R. K. (2020). Coupling the liquid sampling – atmospheric pressure glow discharge, a combined atomic and molecular (CAM) ionization source, to a reduced-format mass spectrometer for the analysis of diverse species. Journal of Analytical Atomic Spectrometry, 35(9), 1910-1921. https://doi.org/10.1039/D0JA00094A