Simulated Moving Bed Chromatographic Processes Research Articles

Moving horizon estimation and control of a binary simulated moving bed chromatographic processes with Langmuir isotherms

Simulated moving bed chromatographic (SMB) chromatographic processes are widely used for separations in pharmaceutical and biotechnological industries. In the present work, the control of such processes is proposed based on a semi-centralized control scheme that utilizes a combination of model predictive control (MPC) and classical PID control. The necessary information from the process, i.e. the internal concentration profiles, for the MPC is obtained by a moving horizon estimator (MHE) in real-time from the available limited measurements (the cycle-averaged concentrations of the extract and raffinate product streams and the dimensionless retention times of the concentration waves in the regeneration zones). As a test case study, the separation of a hypothetical system governed by the Langmuir isotherms in the nonlinear concentration range of the isotherms is considered. First, the stand-alone MHE is validated in open loop mode with no plant-model mismatch under deterministic and stochastic conditions. In the latter case, the true measurements are subject to random normally distributed noise. To evaluate the performance of the proposed control strategy, a reference tracking (change of the requirements for both the purities and the retention times) scenario is simulated. The investigated scenarios are: (i) no plant-model mismatch, (ii) MHE with ideal noiseless measurements and finally (iii) MHE under the influence of measurement noise. Results show that the controller is able to follow the change of the references from reduced purity to complete separation and vice versa closely.

Online estimation of optimal operating conditions for simulated moving bed chromatographic processes

A new approach for determining optimal operating conditions for simulated moving bed chromatographic processes is presented. The method is based on recursive online estimation and requires only rough initial estimates. It is based on a simple foot point model of the moving concentration fronts and an online measurement of the corresponding retention times in the different zones of the plant. A mathematical representation of the adsorption isotherms is not required. The method is validated experimentally for the separation of bicalutamide enantiomers.

Control of incomplete separation in simulated moving bed chromatographic processes

Simulated moving bed (SMB) is a continuous chromatographic process used for the separation of fluid mixtures. This paper presents a simple control strategy to handle incomplete separation, which requires tight control to achieve the desired purities. At first, a discrete-time nonlinear model is derived from wave theory, which will be the basis to estimate the position of the adsorption and desorption fronts. Four controllers are designed, two for the position of the concentration waves in zone 1 and 4, and two for the purities at the extract and raffinate outlets. The performance of the control strategy is evaluated with an experimental study of the separation of racemic Bicalutamide enantiomers in a 4 column-SMB.

Individual Column State and Parameter Estimation in the Simulated Moving Bed Process: an Optimization-based Method

The aim of this work is to propose a method for the simultaneous state and parameter estimation of the individual columns in the Simulated Moving Bed chromatographic process based on concentration measurements only in the switched product outlets. The method exploits the fact that the measurements switch from the inlets of the columns to their outlets sequentially. The estimation problem is cast as a dynamic optimization problem where the prediction error of the output profile is minimized. The initial concentrations in the individual columns and the parameters of the columns are treated as degrees of freedom of the optimization problem. As at each outlet the concentrations of one component are very small and therefore are subject to large relative measurement errors for given expected absolute errors of the concentration measurements, measurements for two different points in time, when the extract port and when the raffinate port is at the outlet of the column under consideration are taken into account simultaneously. The effectiveness of the method is demonstrated for the separation of an isopropanolol racemic mixture.

Fault detection and isolation of concentration sensors in simulated moving bed chromatographic processes (SMB)

This paper deals with the problem of observer-based fault diagnosis for a Simulated Moving Bed (SMB) chromatographic process. A fault detection and isolation (FDI) system is designed such that the sensor faults are detected and located. The residual generation is based on a nonlinear varying-parameters observer scheme. The question of stability is addressed in terms of Lyapunov quadratic stability and sufficient conditions are obtained through strict linear matrix inequalities formulation (LMIs).

Optimization of startup and shutdown operation of simulated moving bed chromatographic processes

Abstract This paper presents new multistage optimal startup and shutdown strategies for simulated moving bed (SMB) chromatographic processes. The proposed concept allows to adjust transient operating conditions stage-wise, and provides capability to improve transient performance and to fulfill product quality specifications simultaneously. A specially tailored decomposition algorithm is developed to ensure computational tractability of the resulting dynamic optimization problems. By examining the transient operation of a literature separation example characterized by nonlinear competitive isotherm, the feasibility of the solution approach is demonstrated, and the performance of the conventional and multistage optimal transient regimes is evaluated systematically. The quantitative results clearly show that the optimal operating policies not only allow to significantly reduce both duration of the transient phase and desorbent consumption, but also enable on-spec production even during startup and shutdown periods. With the aid of the developed transient procedures, short-term separation campaigns with small batch sizes can be performed more flexibly and efficiently by SMB chromatography.

Determination of chromatographic separation parameters of tryptophan enantiomers on a Chirosil-SCA chiral stationary phase by using the inverse method based on the initial guesses estimated from elution by characteristic point method

An effective chiral stationary phase (CSP) for enantioseparation of amino acids was established previously by bonding (18-crown-6)-2, 3, 11, 12-tetracarboxylic acid to silica gel. This CSP has recently been commercialized under the name of Chirosil-SCA. As a first step for developing a Chirosil-SCA simulated moving bed chromatographic process for separation of tryptophan enantiomers, the adsorption isotherm and mass-transfer parameters of each tryptophan enantiomer on the Chirosil-SCA CSP were determined in this study while using only water as a mobile phase. For this task, inverse method (IM) was applied on the basis of the initial guesses estimated from elution by characteristic point (ECP) method, which was found to be more advantageous in the aspects of both accuracy and computational efficiency than the case of utilizing individually only IM or ECP method. The results revealed that the adsorption behavior of each tryptophan enantiomer on the Chirosil-SCA could be well described by the Langmuir–Freundlich isotherm. The model predictions based on the determined parameter values were in close agreement with the experimental chromatograms from a series of single-component or mixture pulse tests that were performed under various feed concentrations and flow rates. It was also found that the Langmuir–Freundlich isotherm parameters of each enantiomer were largely affected by temperature. Such a marked dependence of the parameters on temperature was investigated quantitatively. The results of such an investigation indicated that as the temperature decreases, the adsorption affinities of both enantiomers become higher and the heterogeneity of the Chirosil-SCA becomes more pronounced.

Optimal startup operation of simulated moving bed chromatographic processes

SMB represents one of the widely established periodic adsorption processes and its periodic and nonlinear dynamics presents a significant challenge to the formulation and solution of the optimal startup issue. A multistage startup concept allowing to adjust operating conditions stage-wise is proposed. The startup problem is then formulated aiming at driving the system towards the reference cyclic steady state (CSS) in an optimum manner. A tailored decomposition algorithm is developed to tackle the resulting optimization problem and guarantee numerical tractability. The feasibility of the solution approach is demonstrated on a binary separation with nonlinear competitive isotherms. It is found that the new startup policy dramatically reduces transient time and desorbent consumption. The startup performance in terms of product concentration and purity is also evaluated quantitatively.

Comparison of configurations of a four-column simulated moving bed process by multi-objective optimization

Configurations of a four-column simulated moving bed chromatographic process are investigated by multi-objective optimization. Various existing column configurations are compared through a multi-objective optimization problem. Furthermore, an approach based on an SMB superstructure is applied to find novel configurations which have been found to outperform the standard SMB configuration. An efficient numerical optimization technique is applied to the mathematical model of the SMB process. It has been confirmed that although the optimal configuration highly depends on the purity requirement, the superstructure approach is able to find the most efficient configuration without exploring various existing configurations.

Optimal operation of simulated moving bed chromatographic processes by means of simple feedback control

In this contribution, simple methods are presented for controlling a simulated moving bed (SMB) chromatographic process with standard PI (proportional integral) controllers. The first method represents a simple and model-free inferential control scheme which was motivated from common distillation column control. The SMB unit is equipped with UV detectors. The UV signals in the four separation zones of the unit are fixed by four corresponding PI controllers calculating the ratio of liquid and solid flow in the respective separation zone. In order to be able to adjust the product purity a second, model-based control scheme is proposed. It makes use of the nonlinear wave propagation phenomena in the apparatus. The controlled chromatographic unit is automatically working with minimum solvent consumption and maximum feed throughput—without any numerical optimization calculations. This control algorithm can therefore also be applied for fast optimization of SMB processes.

Neural network-based identification of SMB chromatographic processes

In this contribution, the identification problem for the control of nonlinear simulated moving bed (SMB) chromatographic processes is addressed. For process control the flow rates of extract, desorbent, and recycle of the SMB process, and the switching time are the manipulated variables. But these variables influence the process in a strongly coupled manner. Therefore, a new set of input variables is introduced by a nonlinear transformation of the physical inputs, such that the couplings are reduced considerably. The front positions of the axial concentration profile are taken as model outputs. Multilayer feedforward neural networks (NN) are utilized as approximating models of the nonlinear input–output behavior. The gradient distribution of the model outputs with respect to the inputs is used to determine their structural parameters and the network size is chosen by the SVD method. To illustrate the effectiveness of the identification method, a laboratory scale SMB process is used as an example. The simulation results of the identified model confirm a very good approximation of the first principles models and exhibit a satisfactory long-range prediction performance.

Model-based control of a simulated moving bed chromatographic process for the separation of fructose and glucose

Abstract Chromatographic separations are an expanding technology for the separation of high value products, particularly in the area of pharmaceutics, food, and fine chemicals. The simulated moving bed (SMB) process as a continuous chromatographic separation process is an interesting alternative to conventional batch chromatography, and gained more and more impact recently. The SMB process is realized by connecting several single chromatographic columns in series. A countercurrent movement of the bed is approximated by a cyclic switching of the inlet and outlet ports in the direction of the fluid stream. Because of its complex dynamics, the optimal operation and automatic control of SMB processes is a challenging task. This paper presents the design of a model-based optimization and control scheme for SMB chromatographic separation processes and its application to the separation of fructose and glucose. We propose a two-layer control architecture where the optimal operating trajectory is calculated off-line by dynamic optimization based on a rigorous process model. The parameters of the model are adapted based on online measurements. The low-level control task is to keep the process on the optimal trajectory despite disturbances and plant/model mismatch. Here identification models based on simulation data of the rigorous process model along the optimal trajectory are combined with a suitable local controller. The efficiency of the trajectory control algorithm is shown in a simulation study for the separation of fructose and glucose on an 8-column SMB plant.

Reduced Dynamic Models of Simulated Moving Bed Chromatographic Processes

Abstract Simulated moving bed chromatographic processes are an emerging technology, especially in the field of fine chemicals and pharmaceutical products. Because of the complex process dynamics, model-based control of these processes is still an unsolved issue. The process models reported are either very simplified models which are not accurate enough for control purposes or very complex and computationally expensive. All of these models are based on first principles. The purpose of this contribution is to present newly developed reduced linear dynamic process models. The first part of the paper is devoted to an analysis of the physical properties of the system, leading to a specific structure for the reduced model and a clever choice of inputs and outputs. Based on simulation data of the complex model around the optimal operating trajectory, linear time invariant MIMO models are identified. With a rather simple model structure and low order models, a very good agreement between the predictions of the complex and of the reduced model could be achieved.

Modelling and simulation of nonlinear chromatographic separation processes: a comparison of different modelling approaches

Chromatographic processes provide a powerful tool for the separation of multicomponent mixtures in which the components have different adsorption affinities. As an alternative to conventional batch chromatography as a discontinuous process, the simulated moving bed (SMB) process as a continuous chromatographic separation process gained more and more impact recently. Mathematical modelling and simulation of batch chromatographic processes is widely documented in the literature. For the modelling of SMB chromatographic processes two different strategies exist. The first one considers the corresponding true moving bed process neglecting the cyclic switching and thus the dominating dynmics of the process. The second alternative which is considered within this framework is to connect dynamic models of single chromatographic columns while considering the cyclic port switching in order to represent the dynamics of the real process correctly. We here describe three different approaches for the modelling and simulation of chromatographic separation processes with nonlinear adsorption thermodynamics described by the Langmuir isotherm. The first one is a rigorous modelling and numerical simulation approach, the second one is based on the equilibrium theory and proceeds from the analytical solution for binary separation processes based on nonlinear wave propagation. The third approach only includes nonidealities caused by the limited mass transfer rates. All approaches are analyzed and compared with respect to complexity, accuracy and computational time.

Optimal operation of simulated moving bed chromatographic processes

This paper presents a new algorithm for the calculation of optimal operating conditions for simulated moving bed chromatographic processes with linear adsorption isotherms using a mathematical optimisation strategy based on a rigorous dynamic process model. The new approach has a substantially higher accuracy and reliability in comparison to the common design strategies based on steady state models of the corresponding countercurrent process. Potential cost savings in the operation of this very costly separation process can be identified and exploited with modest computational cost. A simulation example for a sugar separation is shown to illustrate the capabilties of the algorithm proposed.

Computationally efficient dynamic modelling and simulation of simulated moving bed chromatographic processes with linear isotherms

This paper presents a new approach for the dynamic simulation of linear chromatographic processes, in particular, for the simulated moving bed (SMB) process. The goal of this work was the development of a computationally efficient model which is needed for model-based process control. Three different modelling and simulation approaches are presented and compared: an analytical solution of the equilibrium model, a closed-form solution of model equations considering both axial dispersion and mass transfer resistance, and a numerical solution of the general rate model. The solutions are compared with respect to complexity, accuracy and computation time. The new developed closed-form solution gives a high accuracy with low computations time.

Modeling of simulated moving bed chromatographic processes with regard to process control design

This paper presents a new approach for the dynamic simulation of linear chromatographic processes, in particular the Simulated Moving Bed (SMB) process. The main goal of this work was the development of a computationally efficient model for the purpose of model based process control. The approach is based on a closed form solution of the model equations considering both axial dispersion and mass transfer resistance. Simulation studies of this new approach in comparison with a conventional simulation approach and an ideal equilibrium model are shown and the results are compared with respect to complexity, accuracy and computation time.