Purpose <p>To develop a scale-down clone screening platform for the intensified fed-batch (IFB) process to allow efficient identification of high expressing clones fitting the IFB culture strategy in bioreactor.</p> Results <p>Three monoclonal antibodies (mAbs) were used in the development and validation of the IFB specific clone screening platform for CHO cells. The IFB platform significantly improved titer levels, achieving an average titer of 8&#xa0;g/L and the highest titer of 9.6&#xa0;g/L. With similar cell viability, lactate profile and titer levels, both the spin tube model and the AMBR250<sup>@</sup> bioreactor system were effective in screening clones suitable for IFB process. The addition of aurintricarboxylic acid (ATA) and uridine in the process optimization led to a further increase in expression levels in both systems, achieving the highest titer of 12.2&#xa0;g/L.</p> Conclusion <p>This IFB-process specific clone screening serves as an alternative platform for industry application that can increase the effectiveness and efficiency of screening high-expressing CHO cell lines for IFB production.</p>

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Establishment of a high-throughput scale-down clone screening platform for intensified fed-batch culture of CHO cells

  • Haiyan Luo,
  • Shuai Wang,
  • Collin Chong,
  • Lile Wang,
  • Xiaojun Sun,
  • Qian Guo,
  • Sam Zhang,
  • Xiaoyue Chen,
  • Hang Zhou,
  • Weichang Zhou

摘要

Purpose

To develop a scale-down clone screening platform for the intensified fed-batch (IFB) process to allow efficient identification of high expressing clones fitting the IFB culture strategy in bioreactor.

Results

Three monoclonal antibodies (mAbs) were used in the development and validation of the IFB specific clone screening platform for CHO cells. The IFB platform significantly improved titer levels, achieving an average titer of 8 g/L and the highest titer of 9.6 g/L. With similar cell viability, lactate profile and titer levels, both the spin tube model and the AMBR250@ bioreactor system were effective in screening clones suitable for IFB process. The addition of aurintricarboxylic acid (ATA) and uridine in the process optimization led to a further increase in expression levels in both systems, achieving the highest titer of 12.2 g/L.

Conclusion

This IFB-process specific clone screening serves as an alternative platform for industry application that can increase the effectiveness and efficiency of screening high-expressing CHO cell lines for IFB production.