Michel Bailly

The “VARICOL” Process: A New Multicolumn Continuous Chromatographic Process

A new continuous chromatographic process is presented. This is in contrast to the known simulated moving bed (SMB) process which employs a synchronous shift of inlet/outlet lines. The basic principle of the new VARICOL process is based on a non-synchronous shift of the inlet/outlet valves in a multicolumn system. A numerical example compares the performances of the new VARICOL process to the well-known SMB process. This study shows that the VARICOL performances can be better than those of the SMB process. For example, a 5-columns VARICOL permits the same purities to be reached as a 6-columns SMB with the same productivity. Interest in the process is also validated experimentally. Both SMB and VARICOL are optimized to reach the highest achievable productivity for given outlet purities. The productivity of a 5-columns system can be improved 18.5% by using the VARICOL process.

Optimization of simulated moving bed and Varicol processes

A new continuous chromatographic process (Varicol) has been presented recently. Its basic principle consists, in contrast to the traditional simulated moving bed (SMB) technology, of an asynchronous shift of the inlet/outlet lines in a multi-column system with a recycle loop. Due to the stronger influence of the discrete dynamics on the plant behavior, the design of a Varicol process requires the use of model-based optimization to take advantage of the very high flexibility of this process. The equilibrium theory which has been successfully applied to SMB by many practitioners fails to predict the region of complete separation accurately. In this paper, we present a rigorous model-based optimization framework, which can handle the SMB and the novel Varicol process in a systematic manner. The feasibility of the approach is demonstrated by the separation of a mixture of propranolol isomers which exhibits a highly non-linear multi-component adsorption behavior. Experimental results are presented and discussed.

Recycling in preparative liquid chromatography

Abstract A comparison is made between the performance achieved in preparative chromatography when using elution, the most usual operating mode of this technique, and the different implementations of recycling. This work is based on the experimental results obtained in the separation of the enantiomers of ketoprofen on a cellulose-based stationary phase, using the various Chromatographic modes. It uses also the modeling of non-linear chromatography to compare the different operating modes considered. Theoretical and experimental results are presented and compared. In some cases, it is possible to achieve simultaneously both an increase in the production rate and a decrease in the amount of eluent needed.

Application of equilibrium theory to ternary moving bed configurations (four+four, five+four, eight and nine zones) I. Linear case.

In this article, different ternary moving bed configurations are studied by determining the working flow-rates of the equivalent true moving bed at the low solvent consumption point using equilibrium theory. This method has been applied for linear adsorption isotherms. The simulated moving bed flow-rates can then be calculated and a final comparison between the performances of each process is given based upon two different objective functions.

Recycle optimization in non-linear productive chromatography—I Mixing recycle with fresh feed

This paper examines the chromatographic separation of two solutes interacting non-linearly with the sorbent, when only partial separation is achieved at the column outlet, and an intermediate cut of the effluent is recycled. It is shown that, for given feed composition and column size, there is an optimum of the amount of fresh feed injected per cycle; alternately, for given feed composition and amount treated per cycle, there is an optimal column length. This optimum is such that interferences of concentration fronts are minimized in the column. The process is analysed using the “equilibrium theory”, which neglects hydrodynamic dispersion and mass-transfer resistances. Complete analytical solutions are given in the optimal situation, for the case of mass-action law equilibria with unity exponents (Langmuir type equilibrium). The theoretical predictions are compared to experimental results for the separation of Na+ from K+ by H+ eluent in chloride solutions, on a commercial cation-exchanger. The results are also compared to “classical” chromatography (without recycle), and to “two-way” chromatography, presented in a previous paper[1]. With respect to “classical chromatography”, for a given product purity, the optimal recycle process is shown to improve product richness (i.e. concentration of product with respect to solvent) and all performance criteria (eluent consumption, sorbent immobilization, productivity). With respect to “two-way” chromatography, it improves sorbent immobilization and productivity, but yields a poorer Na+ product, thus uses more eluent.

Design of a Simulated Moving Bed: Optimal Particle Size of the Stationary Phase

The influence of the particle size on simulated moving bed (SMB) design is studied using the chiral separation of methyl mandelate on Chiralcel OD. The theoretical model of the pressure drop and band dispersion is validated with experimental results obtained with two different particle sizes (20 and 50 μm) using linear adsorption isotherms. The influence of the particle size on the SMB column size and productivity shows that the optimum particle size is 20–25 μm when working with an acceptable column length and a minimum amount of stationary phase. Due to the high cost of the coated silica stationary phases used for chiral separation, the separation cost is thus minimized.

Application of the equilibrium theory to ternary moving bed configurations (4+4, 5+4, 8 and 9 zones): II. Langmuir case

In this article, the overall methodology used to determine the working flow-rates of a true moving bed (TMB) processing langmuirian isotherms compounds is explained. Then it is applied to different ternary configurations (4+4, 5+4, 8 or 9 zones TMB) in order to characterize their performances. Finally the results obtained on all the configurations are compared on a given example. This comparison allows the choice of the more suitable configuration to be used for a given set of compounds.

Adsorption of BSA and Hemoglobin on Hydroxyapatite Support: Equilibria and Multicomponent Dynamic Adsorption

Interactions of Bovin Serum Albumin and Hemoglobin with an hydroxyapatite gel (HA-Ultrogel, Sepracor), have been studied separately in batch experiments. The adsorption isotherms are of the Langmuir type and can be used directly to scale column operations.For adsorption of hemoglobin alone, in column at pH 6.8 (equal to its isoelectric point) we notice that a classical intraparticle transfer model, based on a constant effective diffusion coefficient represents perfectly the symmetrical breakthrough curve. For acid pH values (pH 5.8), Langmuir isotherms of BSA and hemoglobin adsorptions showed a strong curvature, sign of a quite irreversible adsorption and breakthrough curves obtained under these conditions, exhibit a high dissymmetrical shape for both proteins. In that case, a model of diffusion based on the adsorption on two types of independent sites, with two intraparticle transfer coefficients, gives a good representation of the breakthrough for adsorption of both proteins separately.Binary mixtures of these components were prepared and injected in columns packed with the same support. Competitive Langmuir equation, based on the results obtained in monocomponent batch experiments, give a very good fit to our system. The intraparticle transfer in that case seems to be facilitated, and one effective coefficient alone is enough to predict the breakthrough curves obtained. This behaviour may be the result of an increase of the solution ionic strength, and of the smaller irreversibility feature of the adsorption when proteins are in competition.

Thermal fractionation by moving-bed ion exchange: Principles and experiments

Summary A mixture of ionic solutes may be fractionated by using the effect of temperature on the exchange equilibria of these solutes on an ion-exchange resin. We present here predictions and experimental results for the separation of Ca 2+ and K + in a moving-bed system. It is shown that a simple equilibrium model allows one to calculate the operating regime used in the experiments. Results concerning the ternary system Fe 3+ -Cu 2+ -H + are presented, as an extension of the binary model.

A new multicolumn, open-loop process for center-cut separation by solvent-gradient chromatography.

A comprehensive description of a new process--the GSSR (Gradient with Steady State Recycle) process--for center-cut separation by solvent-gradient chromatography is provided, highlighting its versatility, flexibility, and ease of operation. The GSSR process is particularly suited for ternary separation of bioproducts: it provides three main fractions or cuts, with a target product contained in the intermediate fraction. The process comprises a multicolumn, open-loop system, with cyclic steady state operation, that simulates a solvent gradient moving countercurrently with respect to the solid phase. However, the feed is always injected into the same column and the product always collected from the same column as in a batch process; moreover, both steps occur only once per cycle. The GSSR process was experimentally validated in a pilot unit, using the purification of a crude peptide mixture by reversed phase as a proof of concept; the crude mixture is roughly 50% pure and some of its impurities have isocratic retention times very close to that of the target peptide. Experimental results are reported in terms of cyclic steady-state profiles and process performance indicators, which include product purity and yield. A simplified model-based approach, which uses only a few key components of the crude mixture, is employed to assist in the explanation of the process operation. By dynamically adjusting the switching interval while the process is running, to correctly position the composition profile with respect to the outlet ports, pure product satisfying the target specifications--98% purity and 95% recovery--was obtained under stable operation in the pilot unit.