Sungyong Mun

Standing wave design and experimental validation of a tandem simulated moving bed process for insulin purification

A tandem simulated moving bed (SMB) process for insulin purification has been proposed and validated experimentally. The mixture to be separated consists of insulin, high molecular weight proteins, and zinc chloride. A systematic approach based on the standing wave design, rate model simulations, and experiments was used to develop this multicomponent separation process. The standing wave design was applied to specify the SMB operating conditions of a lab‐scale unit with 10 columns. The design was validated with rate model simulations prior to experiments. The experimental results show 99.9% purity and 99% yield, which closely agree with the model predictions and the standing wave design targets. The agreement proves that the standing wave design can ensure high purity and high yield for the tandem SMB process. Compared to a conventional batch SEC process, the tandem SMB has 10% higher yield, 400% higher throughput, and 72% lower eluant consumption. In contrast, a design that ignores the effects of mass transfer and nonideal flow cannot meet the purity requirement and gives less than 96% yield.

Simulated Moving Bed Technologies for Producing High Purity Biochemicals and Pharmaceuticals

Adsorption and Simulated Moving Bed (SMB) processes can be used to purify many chemicals, biochemicals, and pharmaceuticals. 5MB processes usually have significantly higher yield, higher throughput, and lower eluent consumption than batch chromatography. Conventional 5MB systems have been developed for binary separations. Many major products, however, need to be purified from complex multicomponent mixtures. We have developed comprehensive new technologies for multicomponent separation, which include design methods, versatile 5MB equipment, and software tools for process design, simulation, and optimization. The technologies have been tested for the separation of various biochemicals and pharmaceuticals, and are expected to reduce significantly the cost of 5MB process development and purification. This article introduces the fundamental principles of 5MB and investigates the splitting strategies and design method for multicomponent separations. Insulin purification from a ternary mixture is used as an example. Rate model simulations show that the standing wave design can ensure high purity and yield for all splitting strategies. The simulations also show that mass transfer effects must be considered in 5MB design to meet purity requirements and achieve high yields. A decoupled regeneration strategy is developed to avoid gel fouling, and a long-term 5MB experiment proves that the 5MB process with decoupled regeneration for insulin purification is stable.