Real-time Estimation of the Residual Moisture during Desorption with Temperature-based State Observers

Abstract Monitoring the residual moisture during desorption is vital to ensuring the final product quality in many chemical processes. One particular application is the lyophilization of biotherapeutics, e.g., mRNA vaccines, in which the bound water is removed via desorption during secondary drying. Successful liquid removal provides long-term stability for the vaccines, allowing for storage at higher temperature. This article proposes a novel technique for real-time estimation of the residual moisture during desorption, with application to lyophilization. A state observer is employed, which combines temperature measurement and mechanistic understanding of heat transfer and desorption kinetics, without requiring any online concentration measurement. Results from both simulations and experimental data show that the observer can accurately estimate the concentration of bound water in real time for all possible concentration levels, operating conditions, and measurement noise. This framework represents the first state observer for monitoring and control of the residual moisture in desorption-related processes.