Efficient Simulation of Chromatographic Processes Using the Conservation Element/Solution Element Method

Chromatographic separation processes need efficient simulation methods, especially for nonlinear adsorption isotherms such as the Langmuir isotherms which imply the formation of concentration shocks. The focus of this paper is on the space–time conservation element/solution element (CE/SE) method. This is an explicit method for the solution of systems of partial differential equations. Numerical stability of this method is guaranteed when the Courant–Friedrichs–Lewy condition is satisfied. To investigate the accuracy and efficiency of this method, it is compared with the classical cell model, which corresponds to a first-order finite volume discretization using a method of lines approach (MOL). The evaluation is done for different models, including the ideal equilibrium model and a mass transfer model for different adsorption isotherms—including linear and nonlinear Langmuir isotherms—and for different chromatographic processes from single-column operation to more sophisticated simulated moving bed (SMB) processes for the separation of binary and ternary mixtures. The results clearly show that CE/SE outperforms MOL in terms of computational times for all considered cases, ranging from 11-fold for the case with linear isotherm to 350-fold for the most complicated case with ternary center-cut eight-zone SMB with Langmuir isotherms, and it could be successfully applied for the optimization and control studies of such processes

Optimal design and operation of compact simulated moving bed processes for enantioseparations

Simulated moving bed (SMB) chromatography is attracting more and more attention since it is a powerful technique for complex separation tasks. Nowadays, more than 60% of preparative SMB units are installed in the pharmaceutical and in the food in- dustry [SDI, Preparative and Process Liquid Chromatography: The Future of Process Separations, International Strategic Directions, Los Angeles, USA, 2002. http://www. strategicdirections.com]. Chromatography is the method of choice in these ¯elds, be- cause often pharmaceuticals and ¯ne-chemicals have physico-chemical properties which di®er little from those of the by-products, and they may be thermally instable. In these cases, standard separation techniques as distillation and extraction are not applicable. The noteworthiness of preparative chromatography, particulary SMB process, as a sep- aration and puri¯cation process in the above mentioned industries has been increasing, due to its °exibility, energy e±ciency and higher product purity performance. Consequently, a new SMB paradigm is requested by the large number of potential small- scale applications of the SMB technology, which exploits the °exibility and versatility of the technology. In this new SMB paradigm, a number of possibilities for improving SMB performance through variation of parameters during a switching interval, are pushing the trend toward the use of units with smaller number of columns because less stationary phase is used and the setup is more economical. This is especially important for the phar- maceutical industry, where SMBs are seen as multipurpose units that can be applied to di®erent separations in all stages of the drug-development cycle. In order to reduce the experimental e®ort and accordingly the coast associated with the development of separation processes, simulation models are intensively used. One impor- tant aspect in this context refers to the determination of the adsorption isotherms in SMB chromatography, where separations are usually carried out under strongly nonlinear conditions in order to achieve higher productivities. The accurate determination of the competitive adsorption equilibrium of the enantiomeric species is thus of fundamental importance to allow computer-assisted optimization or process scale-up. Two major SMB operating problems are apparent at production scale: the assessment of product quality and the maintenance of long-term stable and controlled operation. Constraints regarding product purity, dictated by pharmaceutical and food regulatory organizations, have drastically increased the demand for product quality control. The strict imposed regulations are increasing the need for developing optically pure drugs.(...

Modeling of liquid-solid circulating fluidised bed for continuous purification of Kafirin

The thesis presents a comprehensive model for an ion-exchange liquid-solid circulating fluidized bed system for continuous purification of sorghum seed protein kafirin. A model based on tanks-in-series framework is developed and validated. Experimental characterization of equilibrium and kinetic behaviour of kafirin adsorption on different adsorbents is performed. Model based sensitivity analysis and system optimization under various operating conditions demonstrates its usefulness in design and scale-up. The model can also be used other proteins purification systems

Continuous prediction technique for fast determination of cyclic steady state in simulated moving bed process

In the simulation of cyclic processes, such as simulated moving bed (SMB), the system should be equilibrated to reach a cyclic steady state (CSS) before evaluating the process performance. However, the conventional method of successive substitution is quite time-consuming. In this work, a continuous predicting method (CPM) is developed for fast determination of CSS in SMB. In CPM, the direct prediction of state variable at CSS and solving model equation are conducted alternately until CSS is reached. In order to give a guideline for the selection of the acceleration factor, CPM is applied on SMB process for enantio separation of 1,1'-bi-2-naphtol racemate and with the optimized acceleration factor, 59% of computation time saved compared with successive substitution. In addition, this method is further successfully used in a sugar separation process. Given its efficiency and simplicity, this method could provide a useful tool for SMB simulations

Efficient simulation of chromatographic separation processes

This work presents the development and testing of an efficient, high resolution algorithm developed for the solution of equilibrium and non-equilibrium chromatographic problems as a means of simultaneously producing high fidelity predictions with a minimal increase in computational cost. The method involves the coupling of a high-order WENO scheme, adapted for use on non-uniform grids, with a piecewise adaptive grid (PAG) method to reduce runtime while accurately resolving the sharp gradients observed in the processes under investigation. Application of the method to a series of benchmark chromatographic test cases, within which an increasing number of components are included over short and long spatial domains and containing shocks, shows that the method is able to accurately resolve the discontinuities and that the use of the PAG method results in a reduction in the CPU runtime of up to 90%, without degradation of the solution, relative to an equivalent uniform grid

Advances in simulated moving bed : new operating modes : new design methodologies and product (FlexSMB-LSRE) development

Tese de doutoramento. Engenharia Química e Biológica. Faculdade de Engenharia. Universidade do Porto. 200

Optimizing the switching operation in monoclonal antibody production: Economic MPC and reinforcement learning

Monoclonal antibodies (mAbs) have emerged as indispensable assets in medicine, and are currently at the forefront of biopharmaceutical product development. However, the growing market demand and the substantial doses required for mAb clinical treatments necessitate significant progress in its large-scale production. Most of the processes for industrial mAb production rely on batch operations, which result in significant downtime. The shift towards a fully continuous and integrated manufacturing process holds the potential to boost product yield and quality, while eliminating the extra expenses associated with storing intermediate products. The integrated continuous mAb production process can be divided into the upstream and downstream processes. One crucial aspect that ensures the continuity of the integrated process is the switching of the capture columns, which are typically chromatography columns operated in a fed-batch manner downstream. Due to the discrete nature of the switching operation, advanced process control algorithms such as economic MPC (EMPC) are computationally difficult to implement. This is because an integer nonlinear program (INLP) needs to be solved online at each sampling time. This paper introduces two computationally-efficient approaches for EMPC implementation, namely, a sigmoid function approximation approach and a rectified linear unit (ReLU) approximation approach. It also explores the application of deep reinforcement learning (DRL). These three methods are compared to the traditional switching approach which is based on a 1% product breakthrough rule and which involves no optimization