An efficient model development strategy for bioprocesses based on neural networks in macroscopic balances.

In the serial gray box modeling strategy, generally available knowledge, represented in the macroscopic balance, is combined naturally with neural networks, which are powerful and convenient tools to model the inaccurately known terms in the macroscopic balance. This article shows, for a typical biochemical conversion, that in the serial gray box modeling strategy the identification data only have to cover the input-output space of the inaccurately known term in the macroscopic balances and that the accurately known terms can be used to achieve reliable extrapolation. The strategy is demonstrated successfully on the modeling of the enzymatic (repeated) batch conversion of penicillin G, for which real-time results are presented. Compared with a more data-driven black box strategy, the serial gray box strategy leads to models with reliable extrapolation properties, so that with the same number of identification experiments the model can be applied to a much wider range of different conditions. Compared to a more knowledge-driven white box strategy, the serial gray box model structure is only based on readily available or easily obtainable knowledge, so that the development time of serial gray box models still may be short in a situation where there is no detailed knowledge of the system available. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 549-566, 1997.