Simulated Moving Bed Technology Research Articles

Immobilized metal affinity chromatography in open-loop simulated moving bed technology: Purification of a heat stable histidine tagged β-glucosidase

Open-loop simulated moving bed (SMB) has been used for immobilized metal affinity chromatographic (IMAC) purification of his-tagged β-glucosidase expressed in E. coli. A simplified approach based on an optimized single column protocol is used to design the open-loop SMB. A set of columns in the SMB represent one step in the chromatographic cycle i.e. there will be one set each of columns for load, wash, elution etc within the SMB. Only the wash and elution are operated with columns in sequence. The β-glucosidase was purified to almost single band purity with a purification factor of 15 and a recovery of 91%. SMB-performance showed reduced buffer consumption, higher purification fold, a better yield and higher productivity.

Design of a gas phase simulated moving bed for propane/propylene separation

Propylene is one of the world's more important commodities. Nonetheless, its production involves an high energy demanding separation step from a propane–propylene mixture. In this work, an alternative separation of propane–propylene mixtures using simulated moving bed (SMB) technology over 13X zeolite and isobutane as desorbent is presented. Driven by this process novelty, a design strategy for this separation is also proposed, based on three major questions: Is it possible?; Is it reasonable? and Is it worth it? For each question, different approaches are used, starting from equilibrium assumptions through more detailed models, accounting for mass transfer resistances, temperature and pressure drop effects, and presenting, in the end, an introductive note to some relevant aspects for the project evaluation stage. The results show that this separation is possible with the SMB technology, providing high purity propylene ( > 99.5 % ) , at high recovery ( > 99.0 % ) and quite promising productivity values, above 1000 kg of propylene/(m 3 ads h).

Isolation of potato proteins using simulated moving bed technology

The simulated moving bed (SMB) concept of chromatography was applied to treat potato juice from production of starch. The aim was to harvest proteins. SMB offers possibilities to operate with different process strategies and in this study it was shown possible to harvest up to 80% of the protein in a process utilizing very little extra water besides that already present in the juice. After depleting protein from the juice in the adsorption step, the flow through was used to recondition the column after elution. The present study illustrates a new concept of applying chromatography as a capturing step of bulk products.

Equilibrium and Fixed Bed Adsorption of 1‐Butene, Propylene and Propane Over 13X Zeolite Pellets

Propylene‐propane separation is one of the most difficult and demanding energetic operation currently practiced using cryogenic distillation. Extensive studies on various alternatives showed that cyclic adsorption processes, and particularly pressure swing adsorption (PSA), might be an option to replace the traditional distillation. In spite of the promising results of the PSA process, much attention is currently being paid to the simulated moving bed technology (SMB) for gas‐phase separations. The ingenious principle of this process is based on the choice of an adequate adsorbent‐desorbent couple. Thus, in the present work 1‐butene has been studied as an interesting desorbent to displace adsorbed propylene‐propane mixture on 13X zeolite. The measurements of pure 1‐butene adsorption isotherms over 13X zeolite were performed with a gravimetric experimental device for pressure ranging from 0 to 110 kPa and at temperature of 333, 353, 373, and 393 K. The experimental adsorption data were correlated using Toth model. The heat of adsorption at zero coverage and the maximum loading capacity of 1‐butene were found to be 54.4 kJ/mol and 2.10 mol/kg, respectively. The adsorption and desorption of 1‐butene on 13X zeolite packed on a fixed bed initially saturated either by a propane‐propylene mixture or a pure C3 hydrocarbon has been studied. The performance of 1‐butene has been compared with isobutane that was previously proposed to be a highly effective desorbent for C3H6/C3H8 separation. A model based on a double LDF approximation for the mass transfer combined to a heterogeneous energy balance taking into account a variable velocity of the gaseous bulk phase, has been used to describe the breakthrough curves obtained experimentally at 373 K and 110 kPa.

Application of an eremomycin-chiral stationary phase for the separation of dl-methionine using simulated moving bed technology

Recently a new chiral stationary phase (CSP) was introduced, based on the immobilization of the macrocyclic glycopeptide eremomycin to epoxy-activated silica. The application of this new CSP to preparative enantioseparation using simulated moving bed (SMB) chromatography will be presented. MeOH–H 2O (0.1 M NaH 2PO 4) = 20/80 (v/v) was used as the mobile phase to separate the enantiomers of methionine. Successful separation was realized providing productivities around 15 g product/l stat/h for both l and d-methionine under nonlinear conditions. In such delicate continuous chromatographic separation processes, besides productivity, the long-term stability of the applied stationary phases is of importance. Column to column fluctuations were negligible and long-term stability of the preparative stationary phase was satisfactory according to the results of perturbation experiments performed before and after long-term SMB runs.

Efficient optimization of simulated moving bed processes

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 industry [SDI, Preparative and Process Liquid Chromatography: The Future of Process Separations, International Strategic Directions, Los Angeles, USA, 2002. http://www.strategic-directions.com]. Chromatography is the method of choice in these fields, because often pharmaceuticals and fine-chemicals have physico-chemical properties which differ little from those of the by-products, and they may be thermally instable [J. Kinkel, M. Schulte, R. Nicoud, F. Charton, Simulated moving bed (SMB) chromatography: an efficient method for performing large-scale separation of optical isomers, Chiral Eur. 95 (1995) 121–132; J. Strube, A. Jupke, A. Epping, H. Schmidt-Traub, M. Schulte, R. Devant, Design, optimization and operation of chromatographic processes in the production of enantiomerically pure pharmaceuticals, Chirality 11 (1999) 440–450]. In these cases, standard separation techniques as distillation and extraction are not applicable [S. Imamoglu, Simulated moving bed chromatography (SMB) for applications in bioseparation, Adv. Biochem. Eng. Biotechnol. 76 (2002) 211–231]. The use of the SMB technology leads to more efficient operations in terms of dilution and adsorbent utilization than the classical batch separation. Optimization of SMB processes is still a challenging task, particularly when a rigorous first-principles process model is used. SMB processes exhibit strong non-linear behavior and they are of periodic nature. Additionally, their hybrid, non-steady and non-ideal characteristics have to be taken into account. Model-based optimization strategies are therefore of great importance for research and practice. In this article, we report new efficient numerical approaches for the solution of the dynamic optimization problem arising from SMB processes [A. Toumi, Optimaler Betrieb und Regelung von Simulated Moving Bed Prozessen, Dissertation, Fachbereich Bio und Chemieingenieurwesen, University of Dortmund, 2004]. They have been developed in the software package MUSCOD-II [D. Leineweber, Efficient reduced SQP methods for the optimization of chemical processes described by large sparse DAE models, Dissertation, vol. 613, VDI Reihe 3, Verfahrenstechnik, VDI Verlag, 1999], a recent implementation of the direct multiple shooting method where the optimal state trajectory and the corresponding operating parameters are determined simultaneously [H. Bock, K. Plitt, A multiple shooting algorithm for direct solution of optimal control problems, in: Proceedings of the 9th IFAC World Congress Budapest, Pergamon Press, 1984, pp. 243–247; H. Bock, Randwertproblemmethoden zur Parameteridentifizierung in Systemen nichtlinearer Differentialgleichungen, Dissertation, Bonner Mathematische Schriften, 1987, p. 183]. Numerical results show excellent performance for a benchmark enantiomer separation. Finally, the ability to solve the non-linear programs quickly also enables us to consider more challenging operating regimes like VARICOL [P. Adam, R. Nicoud, M. Bailly, O. Ludemann-Hombourger, Process and device for separation with variable-length chromatographic columns, US Patent 6,413,419 (2002)] and PowerFeed [Z. Zhang, M. Mazzotti, M. Morbidelli, PowerFeed operation of simulated moving bed units: changing flow-rates during the switching interval, J. Chromatogr. A 1006 (2003) 87–99].

Understanding and revamping of industrial scale SMB units for p‐xylene separation

AbstractOne of the first applications of Simulated Moving Bed (SMB) technology was in p‐xylene recovery from mixed xylenes. The three main industrial processes for p‐xylene separation from mixed xylenes based on SMB technology are: UOP's Parex, IFP's Eluxyl, and Toray's Aromax. These units operate in liquid phase (T = 180°C and P = 9 bar), achieving high recovery of almost pure p‐xylene with high on‐stream efficiency and extended adsorbent life. In this work, the industrial scale SMB process is investigated from modeling, simulation, and optimization points of view, using experimentally measured xylene adsorption equilibrium and kinetics data on ion exchanged faujasite zeolite. The aim is to develop tools for training of SMB unit operators and choice of the best operating conditions. Useful studies for better understanding of the influence of the operating parameters, adsorbent packing, and separation requirements on unit productivity are presented. SMB unit revamping strategies and operative actions are proposed. The practical application of “separation volume” methodology in the selection of optimum operating conditions that lead to maximum p‐xylene productivity with minimal desorbent consumption is described. © 2006 American Institute of Chemical Engineers AIChE J, 2007

Cromatografia em leito móvel simulado na produção de substâncias enantiomericamente puras ou enriquecidas em larga escala

There is great interest nowadays in the use of preparative liquid chromatography as an effective tool for the production of enantiomerically pure, or enriched, compounds for the pharmaceutical industry. To make the chromatographic process economically attractive, attention is now focused on the choice of the chromatographic operating mode to minimize eluent consumption and to maximize productivity. Among the alternatives to the traditional batch chromatography, attention is now shifting towards simulated moving bed (SMB) technologies and a review covering the latest developments in this area seems timely. Several aspects of this important analytical technique are presented and details concerning the SMB technology for process optimization are outlined.

Simulated Moving Bed Technology for the Industrial Small and Mid Scale Separation of Racemates

Over the last decade in the fine chemical and pharmaceutical industry, simulated moving bed technology has become an import chromatographic method for the separation of racemates. In this report we describe the SMB principle along with its application for the small and mid scale separation of binary mixtures. A practical approach to method development is presented with highlights on the factors that are critical for the design of a robust separation process and its expected productivity. An example of process optimization is also given in regard to the separation of racemic Z-?-homo-alanine.

Simulated moving bed technology: old and new

The Simulated Moving Bed (SMB) concept has been applied to the separation of different mixtures as a continuous counter current separation process, avoiding several problems related with solid motion. The aim of this work is to present some relevant examples of SMB separations corresponding to the two major ages in the use of the SMB concept, here named “old” and “new” applications. The “old” applications of SMB technology in the petrochemical industry are still important, with large and highly productive units; and the “new” applications of the second “age” of SMB concept are from the fine chemical, pharmaceutical and biochemistry areas, associated with the demand of high purity products during the last 10 years.

New aspects on adsorption from supercritical fluid phases

Adsorption from a high pressure gaseous phase, containing as one major component a supercritical fluid is discussed. The fundamentals are presented as a basis of the modelling of the adsorption equilibria. Experimental techniques for determination of adsorption isotherms are presented and examples are given. The modelling of the adsorption isotherms is an essential aspect, e.g. since during application in a chromatographic process, multiple processes of adsorption and desorption are occurring, which are influenced by kinetics, but are mainly determined by thermodynamic equilibrium. In this work the modelling is carried out using the adsorption isotherm proposed by Hill. The application of adsorption processes comprises recovery from the gas phase. Decaffeination and purification of synthetic tocopherol acetate are presented as examples. For the separation of tocopherols and sterols (from natural sources) the selective action of a sequence of adsorption and desorption steps is further discussed. Then, the application of preparative supercritical fluid chromatography (SFC) is investigated. The elution chromatography is compared to the simulated moving bed technology (SMB–SFC).

Analysis of the high-fructose syrup production using reactive SMB technology

This paper deals with the production of high-fructose syrup (HFS) from glucose isomerization using reactive simulated moving bed technology. The reversible reaction is catalyzed by the immobilized enzyme glucose isomerase. In a simulated moving bed reactor (SMBR), reaction and separation processes can be coupled to achieve complete reactant conversion. The isomerization kinetics is experimentally determined at 328 K by the Lineweaver–Burk technique. Basic adsorption data for the sugar isomers (glucose and fructose) were obtained with cationic exchange resin as adsorbent. A mathematical model based on the analogy with true moving bed reactor and its numerical solution based on finite volume method were used for the prediction of the behaviour and performance of a SMBR. A new SMBR configuration for glucose isomerization is proposed and the effect of process parameters on its performance is addressed.

Multi-Component Fractionation in SMB Chromatography for the Purification of Active Fractions from Protein Hydrolysates

Some separations in food and biotechnology concern enrichment of a (multi-component) product in a particular functionality, for instance from a health or nutritional point of view. For instance, when using chromatography, the functionality can be associated to a particular multi-component fraction of an—also—multi-component feedstock. Developing and optimizing an efficient separation has to deal with the inherent multi-component nature of the feedstock and product(s). Simulated moving bed (SMB) chromatographic separations are known for the efficient separation of well-defined bulk chemicals streams such as binary sugar mixtures or xylene isomers. Therefore, this work is focusing on the feasibility of SMB technology for the group of industrially relevant multi-component separation problems. As a typical example, the feasibility of SMB size exclusion chromatography for the isolation of bioactive components, peptides, capable to inhibit the ‘angiotensin-converting enzyme’ (ACE) from a casein hydrolysate for use in functional foods is investigated. Fixed bed (FB) experiments were used to select a proper stationary phase (Toyopearls HW40 C), and buffer, and to determine the partitioning coefficients of the key components. Components with a large volumetric partitioning coefficients (K > 0.75) and a low molecular weight proved to have the highest specific bioactivity. SMB experiments were designed on the basis of measured partitioning coefficients. Three experimental strategies were used to determine the effect of changing ratio of liquid and simulated solid flow rates at constant throughput, a variable throughput and a variable feed concentration, respectively, on the composition, purity and biological activity of the produced fractions, as well as the recovery of the components. High product purities containing the active fraction (> 98%) could be achieved using SMB. Increasing the liquid flow rate at constant simulated resin flow rate (i.e., constant switch time) and throughput yielded an increase in bioactive product purity at the expense of the product recovery. By increasing the throughput, both the purity and recovery of both products were decreased, due to the inevitable presence of ‘intermediate components’. A 10-fold decrease in feed concentration had no clear effect on the separation.

Simulated moving bed technology with a simplified approach for protein purification: Separation of lactoperoxidase and lactoferrin from whey protein concentrate

Simulated moving bed (SMB) technology is a continuous chromatographic technique proven to have many advantages compared to conventional batch chromatography, such as: raised productivity and product concentration, reduced buffer consumption as well as more efficient use of raw material. In this study a 20 column SMB process for the separation of lactoperoxidase and lactoferrin from whey protein concentrate (WPC) was developed. A simplified approach with data from a single column experiment was used when designing the process. The SMB process data were compared to a theoretical scale-up of the breakthrough experiment reflecting the same 20 column set-up run in non-moving bed mode. The outcome of the comparison is a 48% raise in productivity, a 4.3 times decrease in buffer consumption, 6.5 times raise in target protein concentration with a raw material utilization which is slightly better for the SMB process.

Simulated Moving Bed Operation for Size Exclusion Plasmid Purification

AbstractInterest in producing large amounts of plasmid DNA (pDNA) has increased in the last decade as a result of the advances made in gene therapy and DNA vaccines. The last stage of the manufacturing process involves a purification scheme guaranteeing a safe and stable product, considering the authorities' recommendations. This work studies the first step of the purification scheme, i.e., a group separation step based on size exclusion chromatography and using the simulated moving bed technology (SMB). The cleaning in place, crucial for the process validation, is implemented into the SMB in the so‐called CIP‐SMB configuration. Experiments were designed using the simple approach of triangle theory. The feed consisted of a clarified cleared lysate. The results indicate that total recovery of pDNA is possible and that the productivity can be tuned considering the trade‐off with purity. Detailed simulations were used to validate these results after a cleared lysate model was established.

Optimization of SMB Technology Working as a Single Column System

AbstractThe scope of this work was the design, installation, testing and optimization of a pilot plant for simulated moving bed (SMB) chromatography applying the single column technology (ESMB). The working volume of the resin used as the adsorbent changes during loading and regeneration. Resin breathing leads to poor separation performance. In a single packed bed column simultaneous expansion and contraction of the resin bed equalize each other, which leads to a better separation performance. In order to reach industrial targets the SMB unit is optimized by the adaptation of several process parameters. During optimization the behavior of the system with regards to concentration profile and pressure is examined. Other feedback parameters are the purity and yield of the withdrawn liquids. A working diagram is used for the prediction and explanation of the behavior of the process. The standard triangle diagram has been adapted to the particularities of the process.

Simulated Moving Bed Technology in the Reactive Process of Glucose Isomerization

The glucose isomerization process coupled with adsorption using simulated moving bed technology to obtain high/higher fructose syrups (HFS) are discussed. The mathematical modeling of this process, based on the equivalence between True Moving Bed Reactor (TMBR) and Simulated Moving Bed Reactor (SMBR) is presented. Reaction and adsorption parameters are determined experimentally. A new configuration of the SMBR is proposed which allows the production of fructose-rich product (90% in purity).

SMB Operation for Three-Fraction Separations: Purification of Plasmid DNA

The Simulated Moving Bed technology is extended to incorporate a cleaning in place step, and it is then applied by exploiting size exclusion chromatography to purify plasmid DNA. Experimental performances are discussed in the light of our theoretical understanding of the SMB behavior.

Improved performance for continuous separation of 1,1′-bi-2-naphthol racemate based on simulated moving bed technology

The success of simulated moving bed (SMB) chromatography for separating difficult or nearly impossible mixture has drawn strong interest in improving its performance in recent years. In this work, experimentally verified mathematical model was used to find the best possible operating conditions for continuous separation of 1,1′-bi-2-naphtol racemate under specified product quality requirement. Equilibrium dispersive model for SMB systems coupled with non-linear equilibrium isotherm and lumped kinetic approximation constitute the mathematical model in simulating the system behavior. Single objective as well as multi-objective optimization with diverse objectives was carried out using a state-of-the-art AI-based non-traditional optimization technique, elitist non-dominated sorting genetic algorithm with jumping genes. The optimization results showed that significant improvement could be achieved depending on desired objectives. Equilibrium triangle theory was used to explain the optimization results.

Modelling and simulation in chemical engineering: Tools for process innovation

The Chemical Engineering Science movement has served well in solving problems from micro to macro scales. Ultimately, as Professor R. Sargent pointed out, it would be better if translated in “Scientific Engineering”.Examples of innovation as a combination of science (concept), technology and process/product will be presented.The first example is perfusion chromatography based on the concept of “diffusivity augmented by convection” and on the technology of fabrication of large-pore packings. The second example, Simulated Moving Bed (SMB), is based on a concept developed to overcome the difficulties in implementing True Moving Bed processes. Technological contributions come from adsorbent materials and rotary valve to simulate the solid movement. SMB is now a key technology for chiral separations. Modelling/Simulation tools provide sound basis for design/operation by using the concept of “separation volume”.The third example is from the area of multifunctional reactors. The SMB technology is extended to the simultaneous reaction/separation.