Simulated moving bed

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In manufacturing, the simulated moving bed (SMB) process is a highly engineered process for implementing chromatographic separation. It is used to separate one chemical compound or one class of chemical compounds from one or more other chemical compounds to provide significant quantities of the purified or enriched material at a lower cost than could be obtained using simple (batch) chromatography. It cannot provide any separation or purification that cannot be done by a simple column purification. The process is rather complicated. The single advantage which it brings to a chromatographic purification is that it allows the production of large quantities of highly purified material at a dramatically reduced cost. The cost reductions come about as a result of: the use of a smaller amount of chromatographic separation media stationary phase, a continuous and high rate of production, and decreased solvent and energy requirements. This improved economic performance is brought about by a valve-and-column arrangement that is used to lengthen the stationary phase indefinitely and allow very high solute loadings to the process.

Contents

In the conventional moving bed technique of production chromatography the feed entry and the analyte recovery are simultaneous and continuous, but because of practical difficulties with a continuously moving bed, the simulated moving bed technique was proposed. In the simulated moving bed technique instead of moving the bed, the feed inlet, the solvent or eluent inlet and the desired product exit and undesired product exit positions are moved continuously, giving the impression of a moving bed, with continuous flow of solid particles and continuous flow of liquid in the opposite direction of the solid particles. [1] [2]

True moving bed chromatography (TMBC) is only a theoretical concept. Its simulation, SMBC, is achieved by the use of a multiplicity of columns in series and a complex valve arrangement, which provides for flow of the feed mixture and solvent, and "eluent" or "desorbent" feed at any column. The valving and piping arrangements and the predetermined control of these allow switching at regular intervals the sample entry in one direction, the solvent entry in the same direction but at a different location in the continuous loop, whilst changing the fast product and slow product takeoff positions to also move in the same direction, but at different relative locations within the loop. [3]

Ref 3 explains that the advantage of the SMBC is high production rate, because a system could be near continuous, whilst its disadvantage is that it only performs one cut in mixtures. Thus, it is well-suited for separation of a binary mixture. With multiple cuts, analogous to a series of distillation columns, multiple compounds can be separated from a mixture of more than two compounds. With regard to efficiency it compares with the simple chromatography technique like continuous distillation does with batch distillation.

Construction

Specifically, an SMB system has two or more identical columns, which are connected to the mobile phase pump, and each other, by a multi-port valve. The plumbing is configured in such a way that:

a) all columns will be connected in series, forming a single continuous loop;
b) typically, between each column there will be provisions for four process streams: incoming feed mixture, exiting purified fast component, exiting purified slow component, and incoming solvent or eluent;

and

c) each process stream (two inlets and two outlets) will proceed in the same direction after a set time (the steptime).

Advantages

SMB provides lower production cost by requiring less column volume, less chromatographic separation media ("packing" or "stationary phase"), using less solvent and less energy, and requiring far less labor.

At industrial scale an SMB chromatographic separator is operated continuously, requiring less resin and less solvent than batch chromatography. The continuous operation facilitates operation control and integration into production plants.

Drawbacks

The drawbacks of the SMB are higher investment cost compared to single column operations, a higher complexity, as well as higher maintenance costs. But these drawbacks are effectively compensated by the better yield and a much lower solvent consumption as well as a much higher productivity compared to simple batch separations.

For purifications, in particular the isolation of an intermediate single component or a fraction out of a multicomponent mixture, the SMB is not as ideally suited. Normally, a single SMB will separate only two fractions from each other, but a series or "train" of SMBs can perform multiple cuts and purify one or more products from a multi-component mixture. SMB is not readily suited for solvent gradients. Solvent gradient purification may be preferred for the purification of some biomolecules. A continuous chromatography technique to overcome the two fraction limit and to apply gradients is multicolumn countercurrent solvent gradient purification (MCSGP). [4]

Applications

In size exclusion chromatography, where the separation process is driven by entropy, it is not possible to increase the resolution attained by a column via temperature or solvent gradients. Consequently, these separations often require SMB, to extend usable retention time differences between the molecules or particles being separated. SMB is also very useful in the pharmaceutical industry, where separation of molecules having different chirality must be done on a very large scale. For the purification of fructose, e.g. in high fructose corn syrup, or amino-acids, biological-acids, etc. on an industrial scale, simulated moving bed chromatography is used in order to improve the economics of the production.

See also

Related Research Articles

Chromatography is a laboratory technique for the separation of a mixture. The mixture is dissolved in a fluid called the mobile phase, which carries it through a system on which is fixed a material called the stationary phase. The different constituents of the mixture have different affinities for the stationary phase. The different molecules stay longer or shorter on the stationary phase, depending on their interactions with its surface sites. So, they travel at different apparent velocities in the mobile fluid, causing them to separate. The separation is based on the differential partitioning between the mobile and the stationary phases. Subtle differences in a compound's partition coefficient result in differential retention on the stationary phase and thus affect the separation.

Distillation Method of separating mixtures

Distillation is the process of separating the components or substances from a liquid mixture by using selective boiling and condensation. Distillation may result in essentially complete separation, or it may be a partial separation that increases the concentration of selected components in the mixture. In either case, the process exploits differences in the relative volatility of the mixture's components. In industrial applications, distillation is a unit operation of practically universal importance, but it is a physical separation process, not a chemical reaction.

High-performance liquid chromatography Technique used in analytical chemistry

High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pass a pressurized liquid solvent containing the sample mixture through a column filled with a solid adsorbent material. Each component in the sample interacts slightly differently with the adsorbent material, causing different flow rates for the different components and leading to the separation of the components as they flow out of the column.

Protein purification is a series of processes intended to isolate one or a few proteins from a complex mixture, usually cells, tissues or whole organisms. Protein purification is vital for the characterization of the function, structure and interactions of the protein of interest. The purification process may separate the protein and non-protein parts of the mixture, and finally separate the desired protein from all other proteins. Separation of one protein from all others is typically the most laborious aspect of protein purification. Separation steps usually exploit differences in protein size, physico-chemical properties, binding affinity and biological activity. The pure result may be termed protein isolate.

Affinity chromatography is a method of separating a biomolecule from a mixture, based on a highly specific macromolecular binding interaction between the biomolecule and another substance. The specific type of binding interaction depends on the biomolecule of interest; antigen and antibody, enzyme and substrate, receptor and ligand, or protein and nucleic acid binding interactions are frequently exploited for isolation of various biomolecules. Affinity chromatography is useful for its high selectivity and resolution of separation, compared to other chromatographic methods.

Column chromatography

Column chromatography in chemistry is a chromatography method used to isolate a single chemical compound from a mixture. Chromatography is able to separate substances based on differential adsorption of compounds to the adsorbent; compounds move through the column at different rates, allowing them to be separated into fractions. The technique is widely applicable, as many different adsorbents can be used with a wide range of solvents. The technique can be used on scales from micrograms up to kilograms. The main advantage of column chromatography is the relatively low cost and disposability of the stationary phase used in the process. The latter prevents cross-contamination and stationary phase degradation due to recycling. Column chromatography can be done using gravity to move the solvent, or using compressed gas to push the solvent through the column.

Thin-layer chromatography

Thin-layer chromatography (TLC) is a chromatography technique used to separate non-volatile mixtures. Thin-layer chromatography is performed on a sheet of glass, plastic, or aluminium foil, which is coated with a thin layer of adsorbent material, usually silica gel, aluminium oxide (alumina), or cellulose. This layer of adsorbent is known as the stationary phase.

Continuous distillation

Continuous distillation, a form of distillation, is an ongoing separation in which a mixture is continuously fed into the process and separated fractions are removed continuously as output streams. Distillation is the separation or partial separation of a liquid feed mixture into components or fractions by selective boiling and condensation. The process produces at least two output fractions. These fractions include at least one volatile distillate fraction, which has boiled and been separately captured as a vapor condensed to a liquid, and practically always a bottoms fraction, which is the least volatile residue that has not been separately captured as a condensed vapor.

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Hydrophilic interaction chromatography

Hydrophilic interaction chromatography is a variant of normal phase liquid chromatography that partly overlaps with other chromatographic applications such as ion chromatography and reversed phase liquid chromatography. HILIC uses hydrophilic stationary phases with reversed-phase type eluents. The name was suggested by Dr. Andrew Alpert in his 1990 paper on the subject. He described the chromatographic mechanism for it as liquid-liquid partition chromatography where analytes elute in order of increasing polarity, a conclusion supported by a review and re-evaluation of published data.

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Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) is a form of chromatography that is used to separate or purify biomolecules from complex mixtures. It was developed at the Swiss Federal Institute of Technology Zürich by Aumann and Morbidelli. The process consists of two to six chromatographic columns which are connected to one another in such a way that as the mixture moves through the columns the compound is purified into several fractions.

Elution

In analytical and organic chemistry, elution is the process of extracting one material from another by washing with a solvent; as in washing of loaded ion-exchange resins to remove captured ions.

Displacement chromatography is a chromatography technique in which a sample is placed onto the head of the column and is then displaced by a solute that is more strongly sorbed than the components of the original mixture. The result is that the components are resolved into consecutive “rectangular” zones of highly concentrated pure substances rather than solvent-separated “peaks”. It is primarily a preparative technique; higher product concentration, higher purity, and increased throughput may be obtained compared to other modes of chromatography.

Two-dimensional chromatography

Two-dimensional chromatography is a type of chromatographic technique in which the injected sample is separated by passing through two different separation stages. Two different chromatographic columns are connected in sequence, and the effluent from the first system is transferred onto the second column. Typically the second column has a different separation mechanism, so that bands that are poorly resolved from the first column may be completely separated in the second column. Alternately, the two columns might run at different temperatures. During the second stage of separation the rate at which the separation occurs must be faster than the first stage, since there is still only a single detector. The plane surface is amenable to sequential development in two directions using two different solvents.

Partition chromatography theory and practice was introduced through the work and publications of Archer Martin and Richard Laurence Millington Synge during the 1940s. The process of separating mixtures of chemical compounds by passing them through a column that contains a solid stationary phase that was eluted with a mobile phase was well known at that time. Chromatographic separation was considered to occur by an adsorption process whereby compounds adhered to a solid media and were washed off the column with a solvent, mixture of solvents, or solvent gradient. In contrast, Martin and Synge developed and described a chromatographic separation process whereby compounds were partitioned between two liquid phases similar to the separatory funnel liquid-liquid separation dynamic. This was an important departure, both in theory and in practice, from adsorption chromatography.

A monolithic HPLC column, or monolithic column, is a column used in high-performance liquid chromatography (HPLC). The internal structure of the monolithic column is created in such a way that many channels form inside the column. The material inside the column which separates the channels can be porous and functionalized. In contrast, most HPLC configurations use particulate packed columns; in these configurations, tiny beads of an inert substance, typically a modified silica, are used inside the column.

Countercurrent chromatography

Countercurrent chromatography is a form of liquid–liquid chromatography that uses a liquid stationary phase that is held in place by centrifugal force and is used to separate, identify, and quantify the chemical components of a mixture. In its broadest sense, countercurrent chromatography encompasses a collection of related liquid chromatography techniques that employ two immiscible liquid phases without a solid support. The two liquid phases come in contact with each other as at least one phase is pumped through a column, a hollow tube or a series of chambers connected with channels, which contains both phases. The resulting dynamic mixing and settling action allows the components to be separated by their respective solubilities in the two phases. A wide variety of two-phase solvent systems consisting of at least two immiscible liquids may be employed to provide the proper selectivity for the desired separation.

Centrifugal partition chromatography is a special chromatographic technique where both stationary and mobile phase are liquid, and the stationary phase is immobilized by a strong centrifugal force. Centrifugal partition chromatography consists of a series-connected network of extraction cells, which operates as elemental extractors, and the efficiency is guaranteed by the cascade.

References

  1. Bailly, M. and Nicoud, R.-M. (LSGC-ENSIC, 1, rue Grandville, 54001 Nancy and SEPAREX, 5, rue Monod, 54250, Champigneulle, France): The simulated moving bed: a powerful process for purification
  2. Rivat, C. and Stoltz, J.F. (Institut national de la santé et de la recherche médicale (France)) (1993). Biotechnology of Blood Proteins — Purification, Clinical and Biological Applications. John Libbey Eurotext. ISBN   2-7420-0007-0.CS1 maint: multiple names: authors list (link)
  3. "What is simulated moving bed chromatography (SMB chromatography)?" (PDF). Retrieved May 7, 2008.
  4. "Continuous polishing processes: MCSGP" (http). Retrieved August 8, 2016.