This work focuses on the modelling, simulation and control of a batch proteincrystallization process that is used to produce the crystals of tetragonal hen egg-white(HEW) lysozyme. First, a model is presented that describes the formation of proteincrystals via nucleation and growth. Existing experimental data are used to developempirical models of the nucleation and growth mechanisms of the tetragonal HEWlysozyme crystal. The developed growth and nucleation rate expressions are used within apopulation balance model to simulate the batch crystallization process. Then, modelreduction techniques are used to derive a reduced-order moments model for the purpose ofcontroller design. Online measurements of the solute concentration and reactortemperature are assumed to be available, and a Luenberger-type observer is usedto estimate the moments of the crystal size distribution based on the availablemeasurements. A predictive controller, which uses the available state estimates, is designedto achieve the objective of maximizing the volume-averaged crystal size whilerespecting constraints on the manipulated input variables (which reflect physicallimitations of control actuators) and on the process state variables (which reflectperformance considerations). Simulation results demonstrate that the proposed predictivecontroller is able to increase the volume-averaged crystal size by 30% and 8.5%compared to constant temperature control (CTC) and constant supersaturationcontrol (CSC) strategies, respectively, while reducing the number of fine crystalsproduced. Furthermore, a comparison of the crystal size distributions (CSDs)indicates that the product achieved by the proposed predictive control strategy haslarger total volume and lower polydispersity compared to the CTC and CSCstrategies. Finally, the robustness of the proposed method (achieved due to thepresence of feedback) with respect to plant-model mismatch is demonstrated. Theproposed method is demonstrated to successfully achieve the task of maximizingthe volume-averaged crystal size in the presence of plant-model mismatch, andis found to be robust in comparison to open-loop optimal control strategies.
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