Monitoring of Metal Elements in CHO Cell Culture Supernatant Using ICPMS-203

Importance of the Topic

Simultaneous monitoring of trace metal elements in Chinese hamster ovary (CHO) cell culture supernatant is critical for controlling cell metabolism and ensuring the consistent quality of antibody drugs. Changes in metal concentrations such as copper, manganese, and zinc can affect lactate metabolism and glycosylation patterns, which influence yield and therapeutic efficacy.

Objectives and Study Overview

This study demonstrates the use of the ICPMS-2030 for multielement analysis of CHO cell culture supernatant. Two subcloned CHO cell lines were monitored over a six-day culture period to assess temporal changes in metal concentrations and evaluate instrument performance.

Methodology and Instrumentation

Calibration standards were prepared from single-element solutions diluted in 1% (v/v) nitric acid covering concentration ranges suitable for Co, Cu, Fe, Mg, Mn, Mo, Ni, Se, and Zn. Internal standards (Ga, In, Sc, Y) were added automatically. Analytical conditions for the ICPMS-2030 included:

• RF power: 1.2 kW
• Plasma gas flow: 9.0 L/min
• Auxiliary gas flow: 1.1 L/min
• Carrier gas flow: 0.7 L/min
• Nebulizer: 07 UES
• Pump speed: 20 rpm

Samples were 20-fold diluted in 1% nitric acid prior to analysis.

Main Results and Discussion

Spike recovery tests on early, mid, and late-phase supernatants showed limits of quantitation below the observed concentrations and recovery rates within ±20%. Time-course data revealed stable levels of Co, Cu, Fe, Mg, Se, and Zn across both cell lines, while Mn, Mo, and Ni exhibited up to 1.5-fold fluctuations at specific time points. Matrix interference was minimal, confirming high sensitivity and robustness of the ICPMS-2030.

Benefits and Practical Applications

• Rapid, simultaneous quantification of multiple trace metals with simple sample dilution
• High sensitivity and low matrix effects for accurate monitoring
• Supports quality control and optimization in biopharmaceutical production

Future Trends and Opportunities

Integration with real-time bioreactor monitoring, coupling of elemental analysis with metabolomic and proteomic profiling, and development of automated inline sensing are anticipated to enhance process control and product consistency.

Conclusion

The ICPMS-2030 effectively enables multielement monitoring of CHO cell culture supernatants through a straightforward dilution protocol, offering reliable sensitivity and reproducibility for bioprocess monitoring and quality assurance.

References

1. Ryan J. Graham et al., Consequences of trace metal variability and supplementation on Chinese hamster ovary (CHO) cell culture performance: A review of key mechanism and considerations, Biotechnology and Bioengineering, 2019
2. Prabhu et al., Zinc supplementation decreases galactosylation of recombinant IgG in CHO cells, Applied Microbiology and Biotechnology, 2018
3. Application News A634, Direct Analysis of Metallic Elements in Cell Culture Medium by Atomic Absorption Spectrophotometry (AAS)
4. Application News A651, Monitoring of Metal Elements in Cell Culture Supernatant using Atomic Absorption Spectrophotometer
5. Application News 01-0372, Analysis of Metal Elements in Culture Medium Using ICPMS-2030