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Related Experiment Video

Updated: Jan 7, 2026

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Utilizing Cole-Cole parameters for in-line feedback: Cell culture process adjustments based on cell health.

Nithya Krishnan1, Tingting Jiang2, Jacob Crowe3

  • 1Bioprocess Drug Substance Commercialization, Merck & Co., Inc., West Point, Pennsylvania, USA.

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|December 28, 2025
PubMed
Summary

Dielectric spectroscopy monitors cell apoptosis in bioprocessing. This method uses critical frequency and delta epsilon to detect cellular stress, improving cell viability and productivity.

Keywords:
Chinese hamster ovary (CHO) cell cultureDielectric spectroscopyPerfusionProcess analytical technology (PAT)multi‐frequency permittivity

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Area of Science:

  • Biopharmaceutical Process Development
  • Cellular Biology
  • Analytical Chemistry

Background:

  • Effective process control is crucial for biopharmaceutical manufacturing, impacting drug substance quality and yield.
  • Monitoring cell health and apoptosis in real-time is challenging but vital for optimizing bioprocesses.
  • Current methods for detecting apoptosis are often indirect or require offline sampling, limiting timely intervention.

Purpose of the Study:

  • To introduce dielectric spectroscopy as a novel in-line method for monitoring cell apoptosis in biopharmaceutical cultures.
  • To evaluate specific dielectric parameters, critical frequency (fc) and delta epsilon (Δε), as key performance indicators (KPIs) for cell health.
  • To demonstrate the utility of this approach for real-time process monitoring and control in CHO cell cultures.

Main Methods:

  • Utilized dielectric spectroscopy to measure permittivity in Chinese Hamster Ovary (CHO) cell cultures.
  • Analyzed Cole-Cole parameters, specifically critical frequency (fc) and delta epsilon (Δε), to assess cellular changes.
  • Correlated dielectric parameter variations with known cellular stress conditions in batch and perfusion cultures.

Main Results:

  • Dielectric spectroscopy enabled early detection of apoptotic events and associated cellular changes.
  • Variations in critical frequency and delta epsilon correlated significantly with cellular stress responses, including nutrient limitation and high shear.
  • Demonstrated the potential of these dielectric parameters as reliable KPIs for in-line monitoring of cell health.

Conclusions:

  • Dielectric spectroscopy offers a robust framework for real-time, in-line monitoring of cell apoptosis and health in bioprocessing.
  • The identified dielectric parameters provide timely signals for process adjustments, enhancing feeding strategies.
  • This novel approach can lead to improved cell viability, productivity, and overall bioprocess optimization.