Electronic nose for estimation of product concentration in mammalian cell cultivation

The off-gas composition from perfusion cultivation of a CHO-cell line producing recombinant human blood coagulation Factor VIII is monitored with an electronic nose. It is shown that the electronic nose in combination with an artificial neural network can be used for on-line estimation of the Factor VIII concentration in production-scale cultivations. The obtained prediction error (1σ) for the Factor VIII concentration was 1.1 IU/ml. The potential of the electronic nose for estimation of viable cell count is outlined in laboratory-scale Factor VIII cultivations. The obtained prediction error (1σ) for the viable cell count was 0.4×106 cells/ml. The results show that this non-invasive method is potentially useful for on-line bioprocess monitoring.