The application of model-based methods for design and analysis of operational improvements of an industrial glucose isomerization (GI) process is highlighted. First, a multi-scale mathematical model representing important phenomena encountered in the reaction system of a glucose isomerization reactor is developed. Next, model analysis, model identification and model validation based on available reactor operational data are performed. The reactor model is found to describe accurately important phenomena, such as, reaction kinetics, enzyme decay and internal diffusion of the substrate in the enzymatic pellet as a function of the temperature, thereby confirming that the model is ready for use in design-analysis studies. Operation of the GI process is then analyzed in a single reactor and based on this, the reactor model is used as a building block to represent the operation of a GI reactor plant consisting of 10-20 reactors in parallel. The design of the GI plant operation is evaluated through the analysis of simulated results of different operational scenarios. (C) 2016 Elsevier Ltd. All rights reserved.