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Use of High-Throughput Automated Microbioreactor System for Production of Model IgG1 in CHO Cells
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Advanced microscale bioreactor system: a representative scale-down model for bench-top bioreactors.

Wei-Ting Hsu1, Rigzen P S Aulakh, Donald L Traul

  • 1Early Stage Cell Culture, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA, wendyh@gene.com.

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The ambr™ automated bioreactor system accurately mimics 2-L bioreactor performance for Chinese hamster ovary cell cultures, offering an efficient scale-down model. Shake flasks, however, showed significantly lower performance compared to both bioreactor systems.

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Area of Science:

  • Biotechnology
  • Bioprocess Engineering
  • Cell Culture Technology

Background:

  • Automated scale-down bioreactor systems are crucial for efficient cell culture process development.
  • The ambr™ workstation offers individual monitoring and control of dissolved oxygen and pH in single-use bioreactors (10-15 mL working volume).

Purpose of the Study:

  • To evaluate the performance of the ambr™ automated bioreactor system.
  • To compare ambr™ performance against traditional 2-L bench-top bioreactors and shake flasks for recombinant Chinese hamster ovary (CHO) cell culture.

Main Methods:

  • Fed-batch culture of four recombinant CHO cell lines was performed in parallel using ambr™, 2-L bioreactors, and shake flasks.
  • Key culture parameters including environmental controls (temperature, dissolved oxygen, pH), growth, viability, metabolites (glucose, lactate), osmolality, titer, and product quality were monitored.

Main Results:

  • The ambr™ system demonstrated comparable environmental control to 2-L bioreactors.
  • Culture performance metrics (growth, viability, metabolites, osmolality, titer, product quality) in ambr™ closely matched those in 2-L bioreactors.
  • Shake flask cultures exhibited significantly lower performance and less reliable environmental control compared to both ambr™ and 2-L bioreactors.

Conclusions:

  • The ambr™ system serves as a reliable and effective scale-down model for CHO cell fed-batch processes.
  • It accurately predicts performance seen in larger-scale 2-L bioreactors, enhancing process development efficiency.
  • Shake flasks are not suitable for comparable performance evaluation in this context.