Macroscopic modeling of biological cell cultures involves two major steps: (a) the selection of a reaction scheme and (b) the determination of the reaction kinetics. The first step is usually accomplished based on prior knowledge, experimental investigation and trials and errors. This procedure can be time consuming, and more importantly, can lead to the selection of a reaction scheme omitting some important reaction pathways, or at the opposite, incorporating too many details (at least considering the data at hand and the modeling objectives). This paper addresses this modeling problem, and aims at the development of a method for systematically evaluating (i.e. setting up and comparing) all potential reaction schemes, based on a set of measured components, and satisfying structural identifiability properties. One of the main features of the method is that the yield (or pseudo-stoichiometric) coefficients can be estimated independently of the kinetics. The method is illustrated with simulation results and an experimental case study.

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