Monitoring cellular state transitions in a production-scale CHO-cell process using an electronic nose

An electronic nose is used to monitor the bioreactor off-gas composition in perfused cultivations of a CHO-cell line producing recombinant human blood coagulation factor VIII. The applicability of the electronic nose for moni toring cellular state transitions and process control is explained. Tt is s hown that the instrument can reveal characteristic process states related t o product and lactate formation, and detect microbial infections in a very early stage of the infection. The visualization of ideal process conditions is realized by using principal component analysis (PCA) and the on-line ap plicability of this method is outlined. The results illustrate the potentia l of the electronic nose as on-line sensor for ensuring product and process quality in production-scale bioprocesses. (C) 2000 Elsevier Science B.V. A ll rights reserved.