loading page

A Novel Approach Using Real-time Dynamic Imaging Analysis to Monitor Cellular Apoptosis, Viability, and Cell Density in CHO Cell-based Bioprocesses for Monoclonal Antibody Production.
  • +4
  • Claudia Corredor,
  • Yuxiang Zhao,
  • Suyang Wu,
  • Drennen James,
  • Tod Canty,
  • Justin Halbach,
  • Carl Anderson
Claudia Corredor
Bristol Myers Squibb Co

Corresponding Author:claudia.corredor@bms.com

Author Profile
Yuxiang Zhao
Bristol Myers Squibb Company
Author Profile
Suyang Wu
Duquesne University
Author Profile
Drennen James
Duquesne University
Author Profile
Tod Canty
HeartWare Inc
Author Profile
Justin Halbach
HeartWare Inc
Author Profile
Carl Anderson
Duquesne University
Author Profile

Abstract

The biopharmaceutical industry continually seeks innovative approaches to optimize monoclonal antibody (mAb) production, aligning with patient demands, cost-effectiveness, and revenue growth. Chinese hamster ovary (CHO) cells play a pivotal role in mAb production. However, undesired massive CHO cell death can adversely impact productivity, necessitating preventive control operations. To ensure effective control and mitigate the negative impact of cell death, real-time or near real-time monitoring of cell health status is crucial. Bioprocess operators can promptly identify deviations from the desired cell status and take appropriate actions to maintain optimal conditions for mAb production. Additionally, in-process cell status information enhances process understanding, providing valuable insights into the underlying mechanisms governing cell behavior and maximizing productivity. In this study, we investigated an innovative approach, Canty TM dynamic imaging analysis (DIA), as a promising solution for real-time monitoring of cellular apoptosis, viability, and cell density. The conventional trypan blue exclusion method (Vi-CELL TM) and To-Pro-3 fluorescent dye staining (flow cytometry) were used as standard reference methods. Our findings revealed that the Canty TM DIA method combined with appropriate mathematical modeling yielded results comparable to those obtained from Vi-CELL TM and flow cytometry methods. Canty TM DIA successfully traced the trajectory of cell death progress, detecting the onset of apoptosis earlier than the following cell death event. This early detection capability would allow timely intervention to prevent further cell death and maintain optimal productivity. Furthermore, Canty TM DIA demonstrated superior performance in distinguishing images of aggregated cells, providing a more accurate measure of total cell density. This improved accuracy is crucial for calculating viable cell density, which reflects the overall health status of the cells. The results highlight the potential of Canty TM DIA as a powerful tool for real-time monitoring of cell status throughout mAb production processes.