Modeling of analytical, preparative and industrial scale counter-current chromatography separations.

Analytical, preparative and industrial scale counter-current chromatography (CCC) processes differ in the volumes of the loaded solution of components to be separated and in the design of the equipment. Preliminary mathematical modeling is necessary for selection of the optimal design and operation mode of these CCC separations. This study aims to compare simulations of CCC separations at different scales, using an exact description based on the model of equilibrium cells and a much simpler approximate solution based on the Gaussian distribution. Equations for modeling CCC separations of different scales and examples of simulation these separations are presented. It is shown that the discrepancy between the two simulations increases with an increase in the volume of the loaded solution of the components and a decrease in the number of equilibrium cells of a CCC device. In analytical and preparative separations, which are based on complex centrifugal devices, and relatively small sample volumes are injected, approximate equations can be used to simulate various options of CCC separation. In industrial-scale CCC separations, large volumes of the solution of components may be loaded, and as we have proposed previously, these separations can be based on a cascade of mixer-settler extractors. In this case, a more accurate mathematical description based on the cell model equations should be used for modeling.

Modelling and Comparative Analysis of Different Methods of Liquid Membrane Separations.

This article is devoted to a brief review of the modelling of liquid membrane separation methods, such as emulsion, supported liquid membranes, film pertraction, and three-phase and multi-phase extraction. Mathematical models and comparative analyses of liquid membrane separations with different flow modes of contacting liquid phases are presented. A comparison of the processes of conventional and liquid membrane separations is carried out under the following assumptions: mass transfer is described by the traditional mass transfer equation; the equilibrium distribution coefficients of a component passing from one of the phases to another are constant. It is shown that, from the point of view of mass transfer driving forces, emulsion and film pertraction liquid membrane methods have advantages over the conventional conjugated extraction stripping method, when the mass-transfer efficiency of the extraction stage is significantly higher than the efficiency of the stripping stage. The comparison of the supported liquid membrane with conjugated extraction stripping showed that when mass-transfer rates on the extraction and stripping sides are different, the liquid membrane method is more efficient, while when they are equal to each other, both processes demonstrate the same results. The advantages and disadvantages of liquid membrane methods are discussed. The main disadvantages of liquid membrane methods-low throughput and complexity-can be overcome by using modified solvent extraction equipment to carry out liquid membrane separations.

Extraction of Copper from Sulfuric Acid Solutions Based on Pseudo-Liquid Membrane Technology.

Pseudo-liquid membranes are extraction devices in which a liquid membrane phase is retained in an apparatus consisting of two interconnected chambers while feed and stripping phases pass through the stationary liquid membrane phase as mobile phases. The organic phase of the liquid membrane sequentially contacts the aqueous phases of the feed and stripping solutions in the extraction and stripping chambers, recirculating between them. This extraction separation method, called multiphase pseudo-liquid membrane extraction, can be implemented using traditional extraction equipment: extraction columns and mixer-settlers. In the first case, the three-phase extraction apparatus consists of two extraction columns connected at the top and bottom by recirculation tubes. In the second case, the three-phase apparatus consists of a recycling close-loop, which includes two mixer-settler extractors. In this study, the extraction of copper from sulfuric acid solutions in two-column three-phase extractors was experimentally studied. A 20% solution of LIX-84 in dodecane was used as the membrane phase in the experiments. It was shown that the extraction of copper from sulfuric acid solutions in the apparatuses studied was controlled by the interfacial area in the extraction chamber. The possibility of the purification of sulfuric acid wastewaters from copper using three-phase extractors is shown. To increase the degree of extraction of metal ions, it is proposed to equip two-column three-phase extractors with perforated vibrating discs. To further increase the efficiency of extraction using the pseudo-liquid membrane method, it is proposed to use multistage processes. The mathematical description of multistage three-phase pseudo-liquid membrane extraction is discussed.

Three- and Multi-Phase Extraction as a Tool for the Implementation of Liquid Membrane Separation Methods in Practice.

To promote the implementation of liquid membrane separations in industry, we have previously proposed extraction methods called three- and multi-phase extraction. The three-phase multi-stage extraction is carried out in a cascade of bulk liquid membrane separation stages, each comprising two interconnected (extraction and stripping) chambers. The organic liquid membrane phase recycles between the chambers within the same stage. In multi-phase extraction, each separation stage includes a scrubbing chamber, located between the extraction and stripping chambers. The three- and multi-phase multi-stage extraction technique can be realized either in a series of mixer-settler extractors or in special two- or multi-chamber extraction apparatuses, in which the convective circulation of continuous membrane phase between the chambers takes place due to the difference in emulsion density in the chambers. The results of an experimental study of the extraction of phenol from sulfuric acid solutions in the three-phase extractors with convective circulation of continuous membrane phase are presented. Butyl acetate was used as an extractant. The stripping of phenol from the organic phase was carried out with 5-12% NaOH aqueous solutions. The prospects of using three-phase extractors for wastewater treatment from phenol are shown. An increase in the efficiency of three-phase extraction can be achieved by carrying out the process in a cascade of three-phase apparatuses.

Intermittent sample loading technique as a tool for obtaining high- concentration elution bands in recycling liquid-liquid chromatography: Theoretical study of periodic and semi-continuous separation processes.

To improve the efficiency of countercurrent chromatography (CCC) separations, we have previously proposed a new sample loading method called intermittent sample loading (ISL), in which continuous sample feed alternates with short periods of "clean" mobile phase feed to the CCC device. In semi-continuous separation processes, during sample feed periods, the sample is loaded in separate batches, each consisting of a series of intermittent sample loads. It was shown that the application of the intermittent sample loading method in the conventional isocratic CCC separations significantly increased process productivity and the concentration of compounds in the separated fractions. In this study, to further improve the CCC separations with intermittent sample loading, we discuss the application of the ISL method in the processes of close-loop recycling counter-current chromatography (CLR CCC). The advantage of the ISL CLR CCC over the ISL CCC is higher resolution and lower solvent consumption. Equations are presented that allow the simulation of periodic and semi-continuous ISL CLR CCC separations and the selection of optimal operational conditions for these separation processes. It is shown that the use of ISL technique in CLR CCC separations makes it possible to produce fractions of compounds with a much higher concentration than when using the conventional single sample loading method.

Closed-Loop Recycling Dual-Mode Counter-Current Chromatography with Specified Sample Loading Durations: Modeling of Preparative and Industrial-Scale Separations.

We previously reported on a new counter-current chromatography (CCC) operating mode called closed-loop recycling dual-mode counter-current chromatography (CLR DM CCC), which incorporates the advantages of closed-loop recycling (CLR) and dual-mode (DM) counter-current chromatography and includes sequential separation of compounds in the closed-loop recycling mode with the mobile x-phase and in the inverted-phase counter-current mode with the mobile y-phase. The theoretical analysis of several implementations of this separation method was carried out under impulse sample injection conditions. This study is dedicated to the further development of CLR DM CCC theory applied to preparative and industrial separations, where high-throughput operation is required. Large sample volumes can be loaded via continuous loading within a specified time. To simulate CLR DM CCC separations with specified sample loading durations, equations are developed and presented in "Mathcad" software.

A simple and highly efficient counter-current chromatography method for the isolation of concentrated fractions of compounds based on the sequential sample loading technique: Comparative theoretical study of conventional multiple and intermittent sample loading counter-current chromatography separations.

A new modification of the conventional multiple sample loading (MSL) mode - sequential sample loading (SSL) - is suggested to enhance further the performance of the counter-current chromatography (CCC) separation processes. The sequential sample loading technique is simple and easy to implement: the continuous sample solution supply to a CCC column is alternated (interrupted) with short periods of the "pure" mobile phase supply. Periodic (batch) and continuous SSL CCC separations can be designed and implemented. In continuous processes, the sample solution loading is carried out in the form of separate series, consisting of a number of sequential sample solution loads. In this work, the modeling of the conventional multiple sample loading and the sequential sample loading counter-current chromatography is used to compare the two operating modes considered. Equations for the calculation of band profiles, the recovery yield and the purity are given. Equations are also derived permitting the calculation of the optimum operating parameters of the separation processes. It is shown that the use of sequential sample loading makes it possible to produce fractions of purified compounds with a much higher concentration than in the original sample solution. The simulations of the conventional multiple sample loading and the sequential sample loading counter-current chromatography separations are presented in "Mathcad" software.

Analytical, Preparative, and Industrial-Scale Separation of Substances by Methods of Countercurrent Liquid-Liquid Chromatography.

Countercurrent liquid-liquid chromatographic techniques (CCC), similar to solvent extraction, are based on the different distribution of compounds between two immiscible liquids and have been most widely used in natural product separations. Due to its high load capacity, low solvent consumption, the diversity of separation methods, and easy scale-up, CCC provides an attractive tool to obtain pure compounds in the analytical, preparative, and industrial-scale separations. This review focuses on the steady-state and non-steady-state CCC separations ranging from conventional CCC to more novel methods such as different modifications of dual mode, closed-loop recycling, and closed-loop recycling dual modes. The design and modeling of various embodiments of CCC separation processes have been described.

Theoretical study of industrial scale closed-loop recycling counter-current chromatography separations.

Industrial separation technologies can be improved and greatly simplified by using the methods of counter-current chromatography (CCC). We have previously proposed the use of currently available solvent extraction equipment (a series of multistage columns, a cascade of centrifugal mixer-settler extractors) as large-scale CCC devices. For industrial separations, the application of closed-loop recycling counter-current chromatography (CLR CCC) methods seems to be the most promising. To improve the performance of the CLR CCC separations, semi-continuous three-stage processes (1 - continuous loading of the mixture solution over a definite time; 2 - separation of solutes in recycling closed-loop; 3 - elution of the fractions of the separated solutes with the mobile phase) can be used. The purpose of this study is to present a simple and easy to use mathematical model allowing the simulation and design of various options for implementing such separation processes and analyze the influence of its main parameters on separation efficiency.

Modeling of two semi-continuous methods in liquid-liquid chromatography: Comparing conventional and closed-loop recycling modes.

Two high throughput steady-state methods of counter-current chromatography separations: conventional (SS CCC) and closed-loop recycling (SS CLR CCC) are proposed, evaluated and compared. The methods are based on the application of semi-continuous sample loading technique: the CCC setup includes two mobile phase tanks - one with the pure mobile phase and the second - with the sample solution in the mobile phase. The mobile phase pump is periodically switching from one tank to another. The sample solution is continuously loaded into the CCC column over a constant time with the constant volumetric rate equal to the flow rate of the pure mobile phase. Analytical expressions are developed to describe the SS CCC and SS CLR CCC separations with semi-continuous sample loading. Examples of separation of binary and multicomponent mixtures are discussed. The SS CLR CCC has been shown to provide a multiple increase in the performance and effectiveness of CCC devices. Several examples of simulation of SS CLR CCC separation with semi-continuous sample loading are presented in "Mathcad" program. For the experimental verification of the theory, the separation of the binary mixture caffeine/ coumarin was studied. The biphasic solvent system hexane/isopropanol/water (1:1:1), was used. The comparison of experimental and simulated separations demonstrated a reasonable agreement between theory and experiment.

Modeling of closed-loop recycling dual-mode counter-current chromatography based on non-ideal recycling model.

Closed-loop recycling dual-mode counter-current chromatography (CLR DM CCC) includes two separation stages: 1 - closed-loop recycling separation of solutes with mobile x-phase (CLR CCC); 2 - separation of solutes with the mobile y-phase in the opposite flow direction. Previous analysis of CLR DM CCC separations has been limited to the ideal recycling model, which neglects extra-column dispersion. In this study, the analysis of CLR CCC separations is based on the non-ideal recycling model, which takes into account the extra-column dispersion caused by the recycling system. This is of great practical importance, since by selecting the optimal parameters of the recycling system the separation can be significantly improved. Comparative analysis of CLR CCC and CLR DM CCC separations has shown that at low separations factors compounds with low partition coefficients can be separated by CLR CCC using recycling systems with a long recycling line; the separation of compounds with high partition coefficients and the separation of complex mixtures can be performed by CLR DM CCC. Simple equations for simulation and design of CLR DM CCC separations are developed. Several variants of the implementation of this separation method are discussed; examples of simulation are presented in "Mathcad" program.

Closed-loop recycling dual-mode counter-current chromatography. A theoretical study.

Closed-loop recycling dual-mode counter-current chromatography (CLR DM CCC) processes consist of two successive separation stages: separation of solutes in the recycling closed-loop with mobile x-phase and separation of solutes in the counter-current mode with mobile y-phase. Several variants of the implementation of this separation method can be developed: the closed-loop recycling stage may consist of one or several successive separation steps; all components of a mixture can pass through both stages of separation or individual components may be withdrawn from the system at different stages. In this study, such separation processes are theoretically investigated, and simple equations for simulation presented. These equations can help to simulate and select a suitable separation scheme for a given mixture of components. Several examples of separation by CLR DM CCC method are discussed. Examples of simulation are presented in "Mathcad" program. It is shown that CLR DM CCC allows separation of solutes with similar partition coefficients and separation of complex mixtures containing solutes with widely different partition coefficients, providing concentrated fractions of the separated solutes.

Industrial countercurrent chromatography separations based on a cascade of centrifugal mixer-settler extractors.

In hydrometallurgy, traditional extraction technologies, in particular, for isolation and purification of rare-earth metals include a number of processing steps using up to hundreds of mixer-settler extractors. These technologies could be greatly simplified by using the methods of countercurrent chromatography (CCC) separation. However, the current CCC equipment cannot process large volumes of feed material formed during the industrial production of these metals. In this paper, the cascade of centrifugal mixer-settler extractors assembled as a multi-stage unit is suggested for industrial application of CCC and discussed.

Simultaneous concentration and separation of target compounds from multicomponent mixtures by closed-loop recycling countercurrent chromatography.

Closed-loop recycling countercurrent chromatography (CLR CCC) with multiple sample injection has been shown to provide simultaneous concentration and separation of target compounds from multicomponent mixtures. Previous analysis of CLR CCC with multiple sample injections has been limited to the ideal recycling model, which neglects the effects caused by the pump and connecting lines. In this study, an analysis of the process is carried out based on the non-ideal recycling model: recycling chromatograms at two points of the closed-loop - the inlet of the column (A) and the outlet of the column (B) - are considered. The sample is repeatedly introduced at the inlet of the column when the circulating peak of target compound passes point A. Analytical expressions are developed, allowing the design and simulation of different variants of simultaneous separation and concentration of target compounds from multicomponent mixtures. Examples of separation of target compounds from three and five-component mixtures are discussed. Experimental results are presented demonstrating a reasonable agreement between the theory and the experiment. Due to its ability to concentrate individual solutes, CRL CCC with multiple sample injections can become an efficient analytical method to determine minor components in complex mixtures.

An easy-to-use calculating machine to simulate steady state and non-steady-state preparative separations by multiple dual mode counter-current chromatography with semi-continuous loading of feed mixtures.

Multiple dual mode counter-current chromatography (MDM CCC) separation processes with semi-continuous large sample loading consist of a succession of two counter-current steps: with "x" phase (first step) and "y" phase (second step) flow periods. A feed mixture dissolved in the "x" phase is continuously loaded into a CCC machine at the beginning of the first step of each cycle over a constant time with the volumetric rate equal to the flow rate of the pure "x" phase. An easy-to-use calculating machine is developed to simulate the chromatograms and the amounts of solutes eluted with the phases at each cycle for steady-state (the duration of the flow periods of the phases is kept constant for all the cycles) and non-steady-state (with variable duration of alternating phase elution steps) separations. Using the calculating machine, the separation of mixtures containing up to five components can be simulated and designed. Examples of the application of the calculating machine for the simulation of MDM CCC processes are discussed.

Theoretical study of separation and concentration of solutes by closed-loop recycling liquid-liquid chromatography with multiple sample injection.

The method of closed-loop recycling counter-current chromatography (CLR CCC) with multiple sample injection is proposed for the separation and concentration of a target component of a mixture. Analytical expressions are developed to describe the CLR CCC separations with multiple sample injection. Several possible implementations of multiple feed injection are analyzed: the feed is injected in each cycle, after every two cycles and in an arbitrary cycle. The application of different modes of multiple feed injection to the separation and concentration of the target component from binary mixtures by CLR CCC has been studied. The results of this study indicate that it is possible to achieve simultaneously both the separation and concentration of the target component.

Modeling of preparative closed-loop recycling liquid-liquid chromatography with specified duration of sample loading.

The closed-loop recycling counter-current chromatography (CLR CCC) is performed in several consecutive separation stages. First, the loop is opened, and within a specified time the solution of solutes in the mobile phase is continuously fed to the column. After the solutes loading is finished, the loop is closed, and the first separation stage starts. After a certain number of cycles the first fraction of solutes is eluted, the loop is closed, and the second separation stage starts, and so on. In this study, simple equations are presented allowing the simulation of such separation processes. These equations can help to select a suitable compromise between the productivity and the resolution in the preparative and production CLR CCC separations. It is shown that the sample loading time about 20%-30% of the mean residence time is quite acceptable from the practical point of view: proper selection of the loading time and the recycling line length can allow increasing the productivity by an order of magnitude ensuring, a desirable separation.

Theoretical study of closed-loop recycling liquid-liquid chromatography and experimental verification of the theory.

The non-ideal recycling equilibrium-cell model including the effects of extra-column dispersion is used to simulate and analyze closed-loop recycling counter-current chromatography (CLR CCC). Previously, the operating scheme with the detector located before the column was considered. In this study, analysis of the process is carried out for a more realistic and practical scheme with the detector located immediately after the column. Peak equation for individual cycles and equations describing the transport of single peaks and complex chromatograms inside the recycling closed-loop, as well as equations for the resolution between single solute peaks of the neighboring cycles, for the resolution of peaks in the recycling chromatogram and for the resolution between the chromatograms of the neighboring cycles are presented. It is shown that, unlike conventional chromatography, increasing of the extra-column volume (the recycling line length) may allow a better separation of the components in CLR chromatography. For the experimental verification of the theory, aspirin, caffeine, coumarin and the solvent system hexane/ethyl acetate/ethanol/water (1:1:1:1) were used. Comparison of experimental and simulated processes of recycling and distribution of the solutes in the closed-loop demonstrated a good agreement between theory and experiment.

Simple equations to simulate closed-loop recycling liquid-liquid chromatography: Ideal and non-ideal recycling models.

The ideal (the column outlet is directly connected to the column inlet) and non-ideal (includes the effects of extra-column dispersion) recycling equilibrium-cell models are used to simulate closed-loop recycling counter-current chromatography (CLR CCC). Simple chromatogram equations for the individual cycles and equations describing the transport and broadening of single peaks and complex chromatograms inside the recycling closed-loop column for ideal and non-ideal recycling models are presented. The extra-column dispersion is included in the theoretical analysis, by replacing the recycling system (connecting lines, pump and valving) by a cascade of Nec perfectly mixed cells. To evaluate extra-column contribution to band broadening, two limiting regimes of recycling are analyzed: plug-flow, Nec→∞, and maximum extra-column dispersion, Nec=1. Comparative analysis of ideal and non-ideal models has shown that when the volume of the recycling system is less than one percent of the column volume, the influence of the extra-column processes on the CLR CCC separation may be neglected.

Modeling of closed-loop recycling liquid-liquid chromatography: Analytical solutions and model analysis.

In closed-loop recycling (CLR) chromatography, the effluent from the outlet of a column is directly returned into the column through the sample feed line and continuously recycled until the required separation is reached. To select optimal operating conditions for the separation of a given feed mixture, an appropriate mathematical description of the process is required. This work is concerned with the analysis of models for the CLR separations. Due to the effect of counteracting mechanisms on separation of solutes, analytical solutions of the models could be helpful to understand and optimize chromatographic processes. The objective of this work was to develop analytical expressions to describe the CLR counter-current (liquid-liquid) chromatography (CCC). The equilibrium dispersion and cell models were used to describe the transport and separation of solutes inside a CLR CCC column. The Laplace transformation is applied to solve the model equations. Several possible CLR chromatography methods for the binary and complex mixture separations are simulated.