Machine Learning-Powered Optimization of a CHO Cell Cultivation Process.

Journal: Biotechnology and bioengineering
PMID:

Abstract

Chinese Hamster Ovary (CHO) cells are the most widely used cell lines to produce recombinant therapeutic proteins such as monoclonal antibodies (mAbs). However, the optimization of the CHO cell culture process is very complex and influenced by various factors. This study investigates the use of machine learning (ML) algorithms to optimize an established industrial CHO cell cultivation process. A ML algorithm in the form of an artificial neural network (ANN) was used and trained on datasets from historical and newly generated CHO cell cultivation runs. The algorithm was then used to find better cultivation conditions and improve cell productivity. The selected artificial intelligence (AI) tool was able to suggest optimized cultivation settings and new condition combinations, which promised both increased cell growth and increased mAb titers. After performing the validation experiments, it was shown that the ML algorithm was able to successfully optimize the cultivation process and significantly improve the antibody production. The best results showed an increase in final mAb titer up to 48%, demonstrating that the use of ML algorithms is a promising approach to optimize the productivity of bioprocesses like CHO cell cultivation processes clearly.

Authors

  • Jannik Richter
    Institute of Technical Chemistry, Faculty of Natural Sciences, Leibniz University Hannover, Hannover, Germany.
  • Qimin Wang
    Department of Stomatology, Qingdao Municipal Hospital, Qingdao 266071, China.
  • Ferdinand Lange
    Institute of Technical Chemistry, Faculty of Natural Sciences, Leibniz University Hannover, Hannover, Germany.
  • Phil Thiel
    Institute of Technical Chemistry, Faculty of Natural Sciences, Leibniz University Hannover, Hannover, Germany.
  • Nina Yilmaz
    Institute of Technical Chemistry, Faculty of Natural Sciences, Leibniz University Hannover, Hannover, Germany.
  • Dörte Solle
    Institute of Technical Chemistry Gottfried Wilhelm Leibniz University of Hannover Hannover Germany.
  • Xiaoying Zhuang
    Institute of Photonics, Faculty of Mathematics and Physics, Leibniz University Hannover, Hannover, Germany.
  • Sascha Beutel
    Institute of Technical Chemistry, Leibniz University Hannover, Hannover, Germany.