Simulated Countercurrent Research Articles

From batch to continuous chromatographic purification of a therapeutic peptide through multicolumn countercurrent solvent gradient purification

A twin-column Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) process has been developed for the purification of a therapeutic peptide, glucagon, from a crude synthetic mixture. This semi-continuous process uses two identical columns operating either in interconnected or in batch mode, thus enabling the internal recycle of the portions of the eluting stream which do not comply with purity specifications. Because of this feature, which actually results in the simulated countercurrent movement of the stationary phase with respect to the mobile one, the yield-purity trade-off typical of traditional batch preparative chromatography can be alleviated. Moreover, the purification process can be completely automatized.Aim of this work is to present a simple procedure for the development of the MCSGP process based on a single batch experiment, in the case of a therapeutic peptide of industrial relevance. This allowed to recover roughly 90% of the injected glucagon in a purified pool with a purity of about 90%.A comparison between the performance of the MCSGP process and the classical single column batch process indicates that percentage increase in the recovery of target product is +23% when transferring the method from batch conditions to MCSGP, with an unchanged purity of around 89%. This improvement comes at the expenses of a reduction of about 38% in productivity.

Batch chromatography with recycle lag. I—Concept and design

This is the first of a two-part study in which we explore the concept of batch chromatography with recycle lag, concluding with the design, construction, and experimental validation of a prototype that embodies the physical realization of this concept. Moreover, the apparatus is simple to set up in particular in view of large-scale applications. Here the theory behind batch chromatography with recycle lag is revisited and extended, with emphasis on the mathematical formulation and procedure for deriving the single-column batch analogue of any variant of multicolumn simulated countercurrent chromatography. By resorting to selected examples, namely GE Healthcare Bio-science’s three-column periodic countercurrent chromatography, Novasep’s sequential multicolumn chromatography, and a few hypothetical multicolumn processes, we discuss how the theory can be operationalized. Finally, we conclude by describing the design of a device or apparatus—an eluate recycling device (ERD)—to physically realize the proposed concept. The ERD implements an approximate “first in, first out” method for organizing and manipulating the to-be-recycled fractions of eluate collected from the chromatography column, where the oldest (first) amount fluid, or ‘head’ of the fraction, is the first to exit and be recycled to the column.

Extraction of natural compounds using supercritical CO2: Going from the laboratory to the industrial application

Despite industrial application for almost four decades, there is reluctance in some world regions to adopt supercritical (sc) CO2 extraction because of the wrong perception that it is not fully competitive. To refute this misconception, this manuscript analyzes economics of scCO2 extraction of vegetable oil from prepressed seeds. Selection of this application was due to the availability of a predictive mathematical model of the extraction process applicable for simulation purposes; inner microstructural changes of oilseeds during prepressing allow their extraction according to a shrinking core hypothesis. The predictive model has as its single parameter a particle-size and scCO2-condition-independent microstructural mass transfer factor that can be best-fitted to laboratory extractions, existing literature correlations to estimate other model parameters, such as the axial dispersion in packed beds operating with supercritical fluids, and the solubility of vegetable oils in scCO2. On the other hand, there is a need to correlate literature data for the film mass transfer coefficient to unveil the factors responsible for experimental data scattering. Because laboratory or pilot plant runs in single-extraction-vessel units cannot produce the simulated countercurrent contact in an industrial plant having ≥3 extraction vessels, mathematical simulation provides the relationship between oil yield and extraction time that can anchor precise estimations of extraction cost. Analysis of results unveiled differences in optimal extraction time (for minimal extraction cost) between production costs estimated in this work and the operational costs informed before. Because the operational cost does not include the capital cost of the industrial plant, the need appears to reduce its contribution to the total cost by increasing plant productivity. This is achieved reducing extraction time, which negatively influences oil yield.To make further progress in the optimization of industrial scCO2 extraction processes, this manuscript proposes refining the mathematical simulation approach, and studying those technical constraints whose manifestations become more prevalent on scale-up. Mathematical simulation can be adapted to alternative, sample-pretreatment dependent mass transfer mechanisms in the solid matrix. It can be refined also to account for the size distribution of the substrate, radial changes in superficial scCO2 velocity, axial changes in pressure, and radial/axial changes in temperature resulting from heterogeneous packing, pressure drop, and/or heat transfer from/to extraction vessel walls that may influence large-scale extractions. Large-scale experiments will allow studying these phenomena, as well as technical constraints to the decrease in particle size, increase in scCO2 velocity, and decrease in extraction time imposed by the agglomeration and decrease in packed bed permeability of the substrate, and thermal effects during reconditioning of extraction vessels. The latter effects should be included as restrictions in the optimization of the extraction process, which may limit the extraction rate and the size or number of extraction vessel that impact economics positively. Close collaboration with industry will facilitate tackling large-scale problems, as well as refining estimates of plant cost as a function of its size and/or configuration.

Adenovirus purification by two-column, size-exclusion, simulated countercurrent chromatography

Adenovirus serotype 5 (Ad5) was successfully separated by size-exclusion chromatography (SEC) using a simple, yet efficient, two-column, quasi-continuous, simulated moving-bed process operated in an open-loop configuration. The operating cycle is divided into two identical half-cycles, each of them consisting of the following sequence of sub-steps: (i) elution of the upstream column and direction of the effluent of the downstream column to waste; (ii) elution of the upstream column and redirection of its effluent to waste while the downstream column is fed with the clarified bioreaction bulk and its effluent collected as purified product; (iii) operation of the system as in step (i) but collecting the effluent of the downstream column as product; (iv) elution of the upstream column and direction of its effluent to waste while the flow through the downstream column is temporarily halted. Clearance of impurities, namely DNA and host cell protein (HCP), were experimentally assessed. The pilot-scale run yielded a virus recovery of 86%, and a clearance of 90% and 89% for DNA and HCP, respectively, without any fine tunning of the predetermined operating parameters. These figures compare very favorably against single-column batch chromatography for the same volume of size-exclusion resin. However, and most importantly, the virus yield was increased from 57% for the batch system to 86% for the two-column SEC process because of internal recycling of the mixed fractions of contaminated Ad5, even though the two-column process was operated strictly in an open-loop configuration. And last, but not least, the productivity was increased by 6-fold with the two-column process. In conclusion, the main drawbacks of size-exclusion chromatography, namely low productivity and low product titer, were overcome to a considerable extent by an innovative two-column configuration that keeps the mixed fractions inside the system at all times.

Numerical simulation and optimisation of unconventional three‐section simulated countercurrent moving bed chromatographic reactor for oxidative coupling of methane reaction

AbstractThe simulated countercurrent moving‐bed chromatographic reactor (SCMCR) has been reported to significantly enhance methane conversion and C2 product yield for oxidative coupling of methane (OCM) reaction, which is otherwise a low per pass conversion reaction. A mathematical model of an unconventional three‐section SCMCR for OCM was first developed and solved using numerically tuned kinetic and adsorption parameters. The model predictions showed good agreement with available experimental results of SCMCR for OCM. Effects of several process parameters on the performance of SCMCR were investigated. A multi‐objective optimisation problem was solved at the operating stage using state‐of‐the‐art AI‐based non‐dominated sorting genetic algorithm with jumping genes adaptations (NSGA‐II‐JG), which resulted in Pareto Optimal solutions. It was found that the performance of the SCMCR could be significantly improved under optimal operating conditions. © 2011 Canadian Society for Chemical Engineering

Streamlined, two-column, simulated countercurrent chromatography for binary separation

We report on a numerical and experimental study of two-column versions of streamlined, multicolumn, semi-continuous chromatography for binary separation. The systems combine a flexible node design, cyclic flow-rate modulation, and relayed operation of the inlet/outlet ports to extend the mass-transfer zone over the largest possible length, while keeping it inside the system at all times. One advantage of these streamlined designs is the simplicity of their physical realization: regardless of the number of columns, they only require two pumps to supply feed and desorbent into the system, while the flow rates of liquid withdrawn from the system are controlled by material balance using simple two-way valves. In one case, an extra pump is needed to recirculate the fluid in closed-loop. A rigorous model-based optimization approach is employed in the optimal design of the cycles to generate solutions that are physically realizable in the experimental set-ups. The optimized schemes for two-column operation supply fresh feed into the middle of the system where the composition of the circulating fluid is closest to that of the feedstock fluid, and recover the purified products, extract and raffinate, alternately at the downstream end of the unit, while desorbent is continuously supplied into the upstream end of the system. By internally recycling part of the non-pure cut fraction, the scheme with a step of closed-loop recycling significantly reduces its solvent consumption. The feasibility and effectiveness of the reported two-column processes have been verified experimentally on the linear separation of nucleosides by reversed phase subject to 99% purity constraints on both products. It is shown that our processes compare favorably against single-column batch chromatography, steady-state recycling, and four-column, open-loop SMB, for the same amount of adsorbent; they are also better than the four-column, closed-loop SMB at high feed throughputs.

Modeling and simulation of simulated countercurrent moving bed chromatographic reactor for oxidative coupling of methane

Oxidative coupling of methane (OCM) is a reaction of industrial importance but per pass equilibrium conversion and product yield in a single reaction column is severely low. The simulated countercurrent moving bed chromatographic reactor (SCMCR) has been reported to significantly improve the methane conversion and C 2 -product yield. This paper addresses the mathematical modeling of a five section SCMCR for OCM, which is particularly important for understanding the operation of this SCMCR system. In order to obtain the various process parameters, a realistic and rigorous kinetics was adopted in reactors for OCM and subsequently a kinetic model was developed which can best describe the associated kinetics of OCM in SCMCR. Adsorption isotherm parameters were then derived based on the experimental breakthrough curves acquired using single adsorption column. The proposed mathematical model demonstrated extremely good predictions of the experimental results. Finally, effects of operating parameters, such as switching time, methane/oxygen feed ratio, raffinate flow rate, eluent flow rate, etc., on the behavior of the SCMCR were studied systematically.

Multi-objective optimization of simulated countercurrent moving bed chromatographic reactor for oxidative coupling of methane

A comprehensive optimization study on a simulated countercurrent moving bed chromatographic reactor (SCMCR) is reported in this article for oxidative coupling of methane (OCM) reaction. The selection of the operating parameters such as the switching time, make-up feed rate, methane to oxygen ratio in feed, length of columns and flow rates in different sections are not straightforward in an SCMCR. In most cases, conflicting requirements and constraints govern the optimal choice of the decision (operating or design) variables. An experimentally verified mathematical model was selected to optimize the performance of the SCMCR for OCM. A few multi-objective optimization problems were solved for both existing setup and at design stage. The optimization was performed using a state-of-the-art AI-based non-traditional optimization technique, non-dominated sorting genetic algorithm with jumping genes (NSGA-II-JG), which resulted in Pareto optimal solutions. It was found that the performance of the SCMCR could be improved significantly under optimal operating conditions.

Experimental assessment of simulated moving bed and varicol processes using a single-column setup

A novel single-column setup for experimentally reproducing the steady periodic behavior of simulated countercurrent multicolumn chromatography is presented. The system relies on accurate online monitoring of the outlet effluent composition, processing the measured data through a node balance, and feeding it back into the column with an appropriate time delay using a multi-pump configuration to reproduce the desired inlet stream. The feasibility of the proposed system is demonstrated on the linear separation of two nucleosides using three different column configurations, which include both synchronous and asynchronous port switchings. By judiciously selecting the switching interval for process startup and applying a model-based startup procedure, the periodic state can be attained in just one or two cycles. Therefore, mobile phase and solute consumptions required to experimentally reproduce the periodic state of the equivalent multicolumn process are reduced to a minimum. This may be an economic, optimal manner of experimentally testing a set of operating conditions or cycle policy to achieve a given separation performance for a new multicolumn chromatographic separation.

Lysine Adsorption on Cation Exchange Resin. III. Multicolumn Adsorption/Desorption Operation

A model previously developed to describe ion exchange equilibria, kinetics, and column dynamics of lysine adsorption on a strong acid cation exchanger is extended to simulate the cyclic adsorption/desorption of lysine in a multicolumn, simulated countercurrent system. The system simulated comprises an adsorption zone, a desorption zone, and two zones where unadsorbed feed components and excess desorbent are removed. Multiple columns are distributed among the four zones in different simulated countercurrent schemes, including a scheme that allows recycling of excess desorbent and another where the lysine recovery yield is enhanced at low flow rates by lowering the pH in the last column of the adsorption zone. Model predictions are validated by comparison with experimental results obtained in an eight‐column bench scale apparatus and a parametric study is conducted with the model to determine the effects of critical design variables. This research was supported by Ajinomoto Co., Inc.

Analysis of the reverse flow chromatographic reactor

A reverse flow chromatographic reactor with side feed (RFCR) can be used to improve the conversion and selectivity for irreversible and reversible reaction systems beyond the values obtained from conventional steady-state reactors in the case where the reactants are more strongly adsorbed than the products. It is also simpler than conventional chromatographic, moving, and simulated moving beds and other systems that combine reaction and adsorption separation. The results of the study show the robustness and stability of the system, as well as its capacity to significantly improve conversion and selectivity for several reaction systems, including consecutive reactions. Simulation results of this mathematical model for the hydrogenation of 1,3,5-trymethylbenzene (MES) compare well with previous studies, using countercurrent moving-bed reactors and simulated countercurrent bed reactors. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2266–2275, 2004

Simulation of multistage extraction of antioxidants from Chilean hazelnut (Gevuina avellana) hulls

AbstractThe objective of this study was to analyze the factors affecting the ethanol extraction of Chilean hazelnut (Gevuina avellana) hulls to obtain antioxidant compounds. The effects of temperature on the kinetics of polyphenolics extraction and on the antioxidant activities of the extracts were assessed. The radical‐scavenging activities of the extracts were comparable with that of BHA when used at the same concentration. The optimal temperature for the antioxidant activities of the extracts was 40°C. A four‐stage cross‐flow extraction was carried out and a four‐stage countercurrent extraction was simulated, where each stage lasted 30 min. Best results were obtained with countercurrent extraction, which produced an extract that showed 94.4% α,α‐diphenyl‐β‐picrylhydazyl radical inhibition, compared with 86.2% obtained in the first stage of cross‐flow extraction and 92.62% in a batch extraction that lasted 100 h. UV‐vis and NIR spectra of extracts from cross‐flow and from the simulated countercurrent extraction revealed that the composition of extracts varied along the stages and was affected by the operational strategy.

Enhanced Methanol Yields from the Direct Partial Oxidation of Methane in a Simulated Countercurrent Moving Bed Chromatographic Reactor

A laboratory-scale simulated countercurrent moving bed chromatographic reactor (SCMCR) for the direct, homogeneous partial oxidation of methane to methanol has been constructed and tested. Reaction conditions were evaluated from independent experiments with a single-pass tubular reactor. Separation was effected by gas−liquid partition chromatography with 10% Carbowax on Supelcoport. At the optimal reaction conditions of 477 °C, 100 atm, and feed methane-to-oxygen ratio of 16, the methane conversion in the SCMCR was 50%, the methanol selectivity was 50%, and the methanol yield was 25%. Factors affecting methane conversion were investigated. Possible ways to improve the methane conversion, and hence the methanol yield, are discussed.

Further Studies of the Oxidative Coupling of Methane to Ethane and Ethylene in a Simulated Countercurrent Moving Bed Chromatographic Reactor

An experimental and mathematical modeling study of a simulated countercurrent moving bed chromatographic reactor for oxidative coupling of methane to ethane and ethylene is reported. The experiments were done in a laboratory-scale three-section simulated moving bed reactor. Operating conditions were deduced from independent experiments in a microcatalytic fixed-bed reactor and from adsorber dynamics studies. With a YBa2Zr3O9.5 catalyst and activated charcoal adsorbent, the sum of the ethane and ethylene yields at optimum simulated moving bed operating conditions was 45%. Numerical simulations of the reactor performance were done and compared with experimental results.

A simple adsorber dynamics approach to simulated countercurrent moving bed reactor performance

The design and performance of a simulated countercurrent moving bed chromatographic reactor (SCMCR) for high temperature reactions are investigated for both reversible and irreversible reactions of a single reactant. From an analysis of the solid phase and gas phase flow ratios in each of the SCMCR sections, the flow conditions necessary for optimizing the conversion and yield are obtained. Reactor performance is not evaluated from typical material balance equations, but rather by considering the separation of reactant and product waves as they flow through the sections of the SCMCR, and as the feed point is cycled under the assumption of dispersionless plug flow. The additional assumptions of linear adsorption equilibria and infinite gas–solid mass transfer rates permit the expressions for exit molar flow profiles during the initial transient period, and of the ultimate periodic steady state, to be readily obtained. Simple algebraic expressions for the production rate of the reaction product as a function of the adsorption equilibrium constants, the per pass conversion, the number of switching periods, and the molar flow rate of the reactant, are presented.

Continuous chromatographic separation through simulated moving beds under linear and nonlinear conditions

Simulated Moving Bed (SMB) technology is receiving more and more attention as a convenient technique for the production scale continuous chromatographic separation of fine chemicals. Thanks to the efficient simulated countercurrent contact between the stationary and the fluid phase, SMB units can operate under high productivity overload conditions. These lead to nonlinear competitive adsorption behavior, which has to be accounted for when designing and optimising new SMB separations. The so called `Triangle Theory', which is briefly revised here, provides explicit criteria for the choice of the operating conditions of SMB units to achieve the prescribed separation of a mixture characterized by Langmuir, modified Langmuir and bi-Langmuir isotherms. In all these cases, the effect of increasing nonlinearity of the separation, due to increased feed concentration can be predicted. In this paper, the use of this approach for the design of linear and nonlinear SMBs is considered, with reference to examples reported previously. Alternative strategies have been proposed in the literature, which are based on the use of safety factors for linear systems and on an adaptation of this for nonlinear ones. In the cases considered, which involve experimental data for a linear system and numerical experiments for a nonlinear Langmuir system, it is shown that `Triangle Theory' allows attainment of a better understanding of and a deeper insight into the behavior of SMB units.

Optimization of the simulated countercurrent moving-bed chromatographic reactor for the oxidative coupling of methane

This work deals with the further development and optimization of a simulated countercurrent moving bed chromatographic reactor (SCMCR) for the oxidative coupling of methane (OCM). To optimize the adsorptive separation of OCM products from unreacted methane, different adsorbents were selected and tested. Hydrophobic carbon molecular sieve, examined along with other adsorbents (activated charcoal and zeolite with high silica/alumina ratio), appears to be the most suitable choice, both for methane storing and for efficient handling of the OCM separation. Three catalysts, Sm 2O 3, Y 1Ba 2Zr 3O 9.5, and Y 1Ba 2Ge 1O 3.5 have been studied in microcatalytic reactor experiments. The Y 1Ba 2Zr 3O 9.5 catalyst proved to be the best, giving 84% selectivity to C 2-products at a CH 4 O 2 ratio of 11 and nearly complete oxygen conversion. A detailed model of the SCMCR employing experimental information about the catalyst and adsorbent properties was developed to analyze the complex cyclic behavior of the SCMCR. It was found that observed methane loss, and therefore decreased conversion, are caused by incomplete desorption of methane in the carrier section of the SCMCR. This effect can be minimized by selecting a better adsorbent. The influence of the switching time and CH 4 O 2 ratio in the make-up feed, the two most important parameters in this system, on reactor performance was analyzed. It was shown that for the best catalyst (Y 1Ba 2Zr 3O 9.5) at optimal operating conditions the SCMCR can give 55% yield for C2 products at 75% methane conversion. Adaptive flow switching and the use of a non-uniform make-up feed appear to be promising methods for further optimization of the SCMCR.

Preliminary design of a simulated counter-current chromatographic system for the separation of praziquantel enantiomers

An empirical design approach for the separation of praziquantel enantiomers using a simulated counter-current (SCC) chromatographic system is presented. The elution volume of the two components to be separated was determined from batch chromatography and was used to evaluate the flow conditions in each section of the SCC unit. The effectsof the flow-rate and the number of columns in each section, the throughput and the feed concentration on the extract and raffinate purity of the two streams were studied. This design approach provides sufficient accuracy and an adequate representation of the SCC system. It also provides valuable insight into the main factors governing the behaviour of the system.

Experimental evaluation of designs for the simulated countercurrent moving bed separator

AbstractSimulated countercurrent chromatography is a continuous flow method for separation of binary mixtures or for separation of multicomponent mixtures into two fractions. Countercurrent flow is simulated by moving the feed point past several fixed adsorbent beds at a rate between the single column breakthrough time of each component. The number of columns and the location of the inlet and outlet port were varied to investigate product purity and productivity. Concentration profiles of the effluent product streams were measured. The maximum product concentration exceeds the feed concentration during part of the feed‐switching cycle and drops to zero during part of the cycle. Three configurations were tested with the total number of columns varying between three and eight. For the test separation chosen, gaseous propylene and dimethyl ether on Chromosorb 101, high purity (> 99%) product streams were obtained with an optimal four‐column configuration using three desorbent streams.

Numerical simulation of a simulated countercurrent moving bed chromatographic reactor

A mathematical model of a simulated countercurrent moving bed chromatographic reactor (SCMCR) has been developed. The model represents a multiple column reactor consisting of a series of either four or five tubular fixed beds packed with a mixture of catalyst and adsorbent, with a port that can serve either as an inlet or an outlet between each. A reversible first order reaction, A / ag B, with rate coefficients and rate parameters taken from the hydrogenation of 1,3,5-trimethylbenzene is incorporated into the model. The partial differential equations governing the isothermal reactor at 463 K are solved by an adaptive finite element method with uneven grid points. Model predictions of concentration profiles in the columns, and overall reactor performance, are obtained. It is shown that reaction and separation occur simultaneously, and that the conversion of this equilibrium limited reaction is greatly increased over the 0.62 that would be the maximum obtainable in a non-separative system. Under appropriate operating conditions, the model calculations predict that high product purity streams (98–99%) and nearly unit conversions can be obtained.