Three-zone Simulated Moving Bed Research Articles

Separation of Vitexin and Iso-vitexin from Mung Bean Seed Coats Using a Three-Zone Simulated Moving Bed (SMB)

Separation of Vitexin and Iso-vitexin from Mung Bean Seed Coats Using a Three-Zone Simulated Moving Bed (SMB)

Enhanced separation performance of three-zone simulated moving bed chromatography with ModiCon strategy

A three-zone simulated moving bed (SMB) chromatography using ModiCon strategy is proposed to enhance the separating performance. In this approach, three fold-concentrated feed and only desorbent are introduced during one-third and two-thirds of the switching time, respectively. The results showed that if the concentrated feed is introduced during the first and the last subsection of switching time, purity of extract and raffinate are improved, respectively, while recovery and other performance indices (i.e., solvent consumption and ratio of desorbent/feed) are slightly decreased. On the other hand, introduction of concentrated feed during the middle subsection of switching time results in an increase of both raffinate and extract purity, as well as the recovery yield. Other performance indices were comparable to those of three-zone SMB without ModiCon.

Assessment of process configurations to combine enantioselective chromatography with enzymatic racemization

Enantioselective chromatography is nowadays a reliable tool for single enantiomer production from a racemate. The recovery of the distomer by racemization and recycling is a promising method to tackle the 50% yield constraint and to increase the productivity. In this paper three process configurations are compared. The production of enantiopure mandelic acid and methionine enantiomers exploiting different enzymes for racemization are evaluated as part of different chromatographic process configurations. First, the benefits of conventional simulated moving bed (SMB) chromatography in contrast to a single column batch separation unit are assessed in integrated configurations. Then, a concept of coupling the racemization with a simpler three-zone SMB unit, where one regeneration zone is removed, is evaluated.

Relationship between desorbent usage and the recovery of a target product in three-zone simulated moving bed processes designed under the conditions of positive and negative flow-rate-ratios of liquid to solid phases

For a simulated moving bed (SMB) chromatographic process, it has been common knowledge that as desorbent usage increases, the level of separation capability (i.e., the purity and recovery of a target product) continues to improve and then eventually reaches almost a constant level. To check whether there are any exceptional cases concerning such a generally accepted relationship, the effect of desorbent usage on the recovery of a target product under the condition of high purity was investigated using a three-zone SMB process for separation of xylobiose (X2) from a β-xylosidase reaction output. It was found that the considered SMB represented some unusual relationship between desorbent usage and X2 recovery, which also took quite a different pattern according to the searching region for optimal SMB operation parameters. If the optimal operation parameters are determined in the region of positive flow-rate-ratios ("m+ approach"), the use of a larger amount of desorbent than required to make X2 recovery reach a constant level can rather lead to a little reduction in X2 recovery. If the optimal operation parameters are selected in the region of negative flow-rate-ratios ("m− approach"), there exists an optimal desorbent usage, beyond which a further increase in desorbent usage can bring about a significant reduction in X2 recovery. Comparison of the two design approaches reveals that the m− approach can lead to higher X2 recovery and much lower desorbent usage than the m+ approach. Furthermore, such merits of the m− approach over the m+ approach became greater with increasing the SMB throughput.

Enhanced performance of a three-zone simulated moving bed chromatography for separation of succinic acid and lactic acid by simultaneous use of port-location rearrangement and partial-feeding

The performance of a three-zone simulated moving bed (SMB) chromatographic process for separation of succinic acid and lactic acid has been improved to a certain extent in previous researches by applying either a partial-feeding (PF) or a port-location rearrangement (PR) to its operation. To make a further improvement, the strategy of applying both PF and PR simultaneously to the three-zone SMB operation was proposed in this study. The results from both equilibrium-theory analysis and detailed simulation proved that the proposed strategy, which was called PF–PR in this article, had the benefit of a synergy between the individual merits of PF and PR in the three-zone SMB performance. As a consequence, the PF–PR mode could surpass the PF and the PR modes by a wide margin and the classical mode by a dramatic margin in the aspects of separation performance and throughput.

Experimental evaluation of the effect of a modified port‐location mode on the performance of a three‐zone simulated moving‐bed process for the separation of valine and isoleucine

The removal of isoleucine from valine has been a key issue in the stage of valine crystallization, which is the final step in the valine production process in industry. To address this issue, a three-zone simulated moving-bed (SMB) process for the separation of valine and isoleucine has been developed previously. However, the previous process, which was based on a classical port-location mode, had some limitations in throughput and valine product concentration. In this study, a three-zone SMB process based on a modified port-location mode was applied to the separation of valine and isoleucine for the purpose of making a marked improvement in throughput and valine product concentration. Computer simulations and a lab-scale process experiment showed that the modified three-zone SMB for valine separation led to >65% higher throughput and >160% higher valine concentration compared to the previous three-zone SMB for the same separation.

Comparison of the relative merits of port-location rearrangement and partial-feeding as the strategy for improving the performances of a three-zone simulated moving chromatography for separation of succinic acid and lactic acid

The three-zone simulated moving bed (SMB) chromatographic process for separation of succinic acid and lactic acid, which has been developed previously, was based on a classical port-location arrangement (desorbent→extract→feed→raffinate) and a classical feeding mode (full-feeding). To improve the performance of the three-zone SMB process, it is worth utilizing the strategy of either a port-location rearrangement (desorbent→feed→raffinate→extract) or a partial-feeding. To investigate which of the two strategies is more effective, the three-zone SMBs based on the port-location rearrangement (PR) and the partial-feeding (PF) were optimized each under equal conditions and then the two strategies were compared in terms of product purities or throughput. The result showed that the PR strategy led to higher purities or higher throughput than the PF strategy in regard to the previously reported three-zone SMB system. To check whether such trend is still valid in other separation systems, the above optimization works were repeated while varying only the selectivity between two feed components. It was confirmed that the PR strategy is definitely superior to the PF strategy. However, such superiority of the PR over the PF strategy is lessened as the selectivity becomes lower. If the selectivity is significantly low, the PR strategy is rather outperformed by the PF strategy.

Three-port operation in three-zone simulated moving bed chromatography

A new operating method, namely three-port operation in a three-zone simulated moving bed (TT-SMB), was developed to improve the separation performance of simulated moving bed (SMB) chromatography. In the TT-SMB, the switching period consists of two steps; extract outlet port is closed at the first step for raffinate production and raffinate outlet port is closed at the second step for extract production. As a result, three ports were used in each step of the three-zone SMB operation. The separation performance of TT-SMB was compared with conventional three- and four-zone SMBs in terms of purity, recovery, productivity, and eluent consumption. A conventional three-zone SMB operation usually produced the contaminated portion at the product outlet node during the switching period. However, such phenomenon could be prevented by using the TT-SMB operation because one product outlet port was closed at each step. Compared to the conventional three-zone SMB, all performance parameters improved with the use of TT-SMB, and the improvement in purity and recovery was significant (up to 7%). Adjusting the step ratio played a key role in the trade-off between the performance parameters. The purity, recovery, and productivity of TT-SMB at well-designed step ratio conditions are up to 3% higher than those of the conventional four-zone methods (1-1-1-1 configuration).

A three-zone simulated moving-bed for separation of immunoglobulin Y

Separation of immunoglobulin Y (IgY) from hen eggs is an interesting topic for investigating antibody purification. Understanding of IgY separation by chromatography is necessary to prepare antibody. IgY preparation in SMB was simulated by Aspen chromatography and was experimented by assembling a 3-zone simulated moving bed (SMB). With change of stream flow rates, the SMB performance was studied. Simulation of IgY batch HPLC chromatography was also done and confirmed by HPLC experiments. Based on these, good operating conditions of SMB chromatography were determined. Three-zone SMB equipment was set up by connecting three C18-HPLC columns, four HPLC pumps, and six multiposition valves. Batch chromatography of IgY was conducted to determine the isotherms of IgY and contaminating impurity. The outlet streams of SMB, raffinate and extract were sampled and analyzed by analytical HPLC system. The adsorption isotherms of IgY and impurity were determined as HIgY=0.1 and Himpure=1.1. The highest experimental purity of IgY from SMB was obtained as 98% for the operating parameters of Qfeed=0.2mL/min, Qdesorbent=0.31 mL/min, Qextract=0.2 mL/min, Qraffinate=0.3 mL/min, and switching time=8.47 min.

Continuous separation of succinic acid and lactic acid by using a three-zone simulated moving bed process packed with Amberchrom-CG300C

The issue of separating succinic acid and lactic acid in a continuous mode has been a major concern in the biotechnological process for production of succinic acid. To address this issue, both the optimal design and the experimental validation of a three-zone simulated moving bed (SMB) process for such separation were attempted in this article using the Amberchrom-CG300C resin and a self-assembled SMB unit with three zones. First, the intrinsic parameters of the two organic acids on the Amberchrom-CG300 resin were estimated at 40°C from a series of multiple frontal experiments. The resulting intrinsic parameters were then used in optimizing the experimental setting points for pump flow rates and switching time of the three-zone SMB equipment, which was assisted by an up-to-date genetic algorithm. Based on the optimized conditions, the relevant SMB experiment was conducted at 40°C and all the resultant samples from the product ports and column outlets of the SMB unit were assayed. It was confirmed from the assay results that the continuous separation of succinic acid and lactic acid was performed successfully. The experimental data for the product concentration profiles and the internal concentration profiles were also in reasonable agreement with the model predictions.

IgY (Immunoglobulin Yolk) 분리를 위한 3-영역 SMB (Simulated Moving Bed)와 4-영역 SMB 비교전산모사

난황에 포함된 IgY는 포유동물에 있는 바이러스나 항원에 반응하는 항체와 같은 역할을 한다. 난황을 전처리한 후 3-zone와 4-zone SMB를 이용하여 지질단백질들로 부터 IgY를 분리하는 전산모사연구를 수행하였다. 회분식 크로마토그래피에서 전산모사 매개변수와 흡착 등온식 SMB 전산모사 변수를 얻었다. Aspen simulator를 이용하여 전산모사를 수행하여 IgY를 분리할 수 있는 3-zone과 4-zone SMB 운전조건을 비교하여 다음과 같은 결과를 얻었다. IgY와 다른 단백질의 농도와 순도를 모두 고려할 때, 꼭지점인 좌표(<TEX>$m_2$</TEX>, <TEX>$m_3$</TEX>=0.1, 1.1)에서 3-zone SMB가 최적의 조건으로 생각된다. IgY 만을 고려하면 4-zone SMB가 좌표(<TEX>$m_2$</TEX>, <TEX>$m_3$</TEX>=0.06, 0.5)에서 가장 높게 IgY를 분리할 수 있었다. recycle이 없는 3-zone SMB는 꼭지점 좌표에서 좌표이동이 extract의 지질 단백질 농도에 큰 영향을 주었다. IgY (Immunoglobulin Yolk) is a specific antibody in egg yolk, and it protects human body from virus and antigen. There are a lot of egg yolk components such as lipoprotein and protein. To separate IgY, HPLC (High Performance Liquid Chromatography) and precipitation were used in a batch mode and SMB (Simulated Moving Bed) was adopted for continuous purification of yolk proteins. IgY and other proteins in yolk were separated by using three-zone and four-zone SMB chromatography. Before performing SMB experiments, batch chromatography simulation parameters and adsorption isotherms were obtained. The parameters of batch chromatography were used to simulate SMB using Aspen chromatography. To compare three-zone and four-zone SMB chromatography, simulations in <TEX>$m_2-m_3$</TEX> plane on the triangle theory were carried out. In terms of concentration and purity of both IgY and other lipoproteins, 3-zone SMB process is considered as ideal at the vertex of triangle (<TEX>$m_2$</TEX>, <TEX>$m_3$</TEX>=0.1, 1.1). 4-zone SMB yields the highest IgY purity at the coordinate (<TEX>$m_2$</TEX>, <TEX>$m_3$</TEX>=0.06, 0.5), which is the pure raffinate region. In 3-zone SMB without recycle, other lipoproteins in extract are largely affected in purity by small shift from the vertex of triangle (<TEX>$m_2$</TEX>, <TEX>$m_3$</TEX>=0.1, 1.1).

Development of a non-triangular separation region for improving the performance of a three-zone simulated moving bed chromatography for binary separation with linear isotherms

For a three-zone simulated moving bed (SMB) chromatography with linear isotherms, the feasible set of operating parameters for complete separation is known to exist within a triangular region of the triangle theory that is formed in the operating parameter plane spanned by the flow-rate-ratios in the separation zones (II and III), which are commonly denoted as m2 and m3. Such an operating region for complete separation region, however, has been established only in the first quadrant (m2, m3) plane, where m2>0 and m3>0, until now. In this study, a new complete-separation region was developed in the third quadrant (m2, m3) plane, where m2<0 and m3<0, regarding a three-zone SMB process for the first time. The results showed that the new separation region created in the third quadrant (m2, m3) plane took a non-triangular shape. The operating parameters within such a non-triangular separation region were capable of guaranteeing complete separation for an ideal system with no mass-transfer effects. For a non-ideal system with considerable mass-transfer effects, the operating parameters that were selected with a sufficient margin from the boundaries of the non-triangular separation region led to high purities. One of the noteworthy features in the pattern of solute migration for such case was that both low-affinity and high-affinity solutes reached their corresponding product ports after taking a turn around the SMB bed once. Finally, it was confirmed from the results of SMB optimization based on genetic algorithm and detailed model that the operating parameters in the third quadrant (m2, m3) plane, if chosen properly, could ensure higher purities or higher throughput than the optimal operating parameters in the first quadrant (m2, m3) plane.

Novel Simulated Moving-Bed Cascades with a Total of Five Zones for Ternary Separations

Two simulated moving-bed (SMB) cascades are proposed for the separation of a ternary mixture containing the least, medium-, and most retained solutes (A, B, and C). Each cascade has a total of five zones. The first cascade combines two three-zone SMBs sharing zone III: the one SMB with zones I to III separates (A+B+C) into A and (B+C), and the other three-zone SMB with zones III to V separates (B+C) into B and C. The second cascade combines a four-zone SMB consisting of zones I to IV and a three-zone SMB comprising zones IV, V and I: the former separates (A+B+C) into (A+B) and C, and the latter separates (A+B) into A and B. Analysis of the concentration band movement together with a modeling study confirms the feasibilities of the two cascades, suggesting that the first cascade should be adopted if the separation of (A+B) and C is easier than that of A and (B+C), and otherwise, the second cascade should be used.

Optimal design and experimental validation of a three-zone simulated moving bed process based on the Amberchrom-CG161C adsorbent for continuous removal of acetic acid from biomass hydrolyzate

In the production process of bio-ethanol from biomass, acetic acid is recognized as the key impurity to be removed from the sugar components that are generated by hydrolyzing biomass. In regard to this issue, it has recently been confirmed that the Amberchrom-CG161C resin was highly qualified as the adsorbent of a simulated moving bed (SMB) process for continuous separation of acetic acid from the biomass hydrolyzate, i.e., sugars. However, the previous study on the Amberchrom-CG161C SMB with the aforementioned separation goal has been limited to only a theoretical work, including some batch-chromatography tests. The experimental validation of such an Amberchrom-CG161C SMB process, including its optimal design, was attempted in this article. This task began by assembling the experimental unit of the SMB process with three zones. Its operating conditions were then optimized by using genetic algorithm. Under the optimized operating conditions, the relevant three-zone SMB experiment was conducted. The assay of all the resultant product samples verified that the SMB separation of interest was performed successfully as designed. The experimental data were also found to agree closely with the model predictions. Finally, a partial-discard strategy was applied to maintain the sugar product concentration as high as possible.

Strategy of rearranging the port locations in a three-zone simulated moving bed chromatography for binary separation with linear isotherms

A three-zone simulated moving bed (SMB) chromatographic process for binary separation, which has been developed previously, was reported to have four ports that are located in the order of desorbent, extract, feed, and raffinate. To make a substantial improvement in the performance of such a three-zone SMB process, the strategy of rearranging the port locations was proposed in this study within a linear isotherm region. The core of the proposed strategy is to transfer the location of the extract port from its classical position (i.e., the position between zones I and II) to the zone III outlet. Simultaneously, the feed and raffinate ports are transferred backwards by one zone. Thus, the order of the proposed port locations follows the order of desorbent, feed, raffinate, and extract. The results from both equilibrium-theory analysis and detailed simulation proved that the proposed strategy was highly effective in improving the product purities or throughput of a three-zone SMB process. Furthermore, it was found that such advantage of the proposed strategy became greater as the difference between the adsorption affinities of the feed components was larger.

Three-zone simulated moving-bed (SMB) for separation of cytosine and guanine

Separation of guanine and cytosine base pairs in nucleotide is an interesting topic for investigation of DNA structure. Therefore, an understanding of nucleotide separation by chromatography is necessary to prepare DNA molecules. Guanine and cytosine separation in SMB was simulated by Aspen chromatography and it was experimented by assembled 3-zone simulated moving bed (SMB) with change of stream flow rates, sample concentration, and desorbent flow rate. The simulation of batch chromatography was also confirmed by HPLC experiments. Based on these, good operating conditions of SMB chromatography were determined. Three-zone SMB equipment was set up by connecting three C18-HPLC columns, four HPLC pumps, and six multiposition valves. Batch chromatography of cytosine and guanine was conducted to determine the isotherms of the two nucleotides. The outlet streams of SMB, raffinate and extract were sampled and analyzed by analytical HPLC system. The adsorption isotherms of cytosine and guanine were HC= 0.5 and H G =1.05. The highest experimental purity of cytosine and guanine in SMB was obtained as 94.9% and 89.8% with operating parameters of Q feed =0.2 mL/min, Q desorbent =0.6 mL/min, Q extract =0.2 mL/min, Q raffinate =0.6 mL/min, and switching time=7 min.

SMB(Simulated Moving Bed)를 이용한 IgY(Immunoglobulin Yolk) 분리의 전산모사

난황에 포함된 IgY는 포유동물에 있는 바이러스나 항원에 반응하는 항체와 같은 역할을 한다. IgY 분리를 위해 난황을 전처리한 후 3-zone SMB를 이용하여 지질단백질들로 부터 분리하는 전산모사연구를 수행하였다. 회분식 크로마토그래피와 pulse input method(PIM) 실험을 이용하여 전산모사 매개변수와 흡착 등온식을 얻었다. Aspen simulator를 이용하여 전산모사를 수행하여 IgY를 분리할 수 있는 SMB 운전조건을 다음과 같이 제시할 수 있었다. 삼각형 이론의 <TEX>$m_2$</TEX>와 <TEX>$m_3$</TEX> 값은 각각 0.18, 1.0이고 스위칭 타임은 419 초이었다. 전산모사 결과 raffinate의 IgY 순도가 98.39%이고 두번째 싸이클에서 순도가 정상상태에 도달하였다. IgY(Immunoglobulin Yolk) is a specific antibody in egg yolk, and it protects human body from virus and antigen. There are a lot of egg yolk components such as lipoprotein and protein. To separate IgY, HPLC(High Performance Liquid Chromatography) and precipitation were used in a batch mode and SMB(Simulated Moving Bed) was adopted for continuous purification of yolk proteins. IgY and other proteins in yolk were separated by using three-zone SMB chromatography. Before performing SMB experiments, batch chromatography and PIM(pulse input method) were performed to find operation parameters and adsorption isotherms. The results of batch chromatography were compared with simulated results using Aspen chromatography. To find the most suitable separation condition in SMB chromatography, simulations in <TEX>$m_2$</TEX>-<TEX>$m_3$</TEX> plane on the triangle theory were carried out. <TEX>$m_2$</TEX> = 0.18, <TEX>$m_3$</TEX> = 1.0 and <TEX>${\Delta}$</TEX>t = 419 s are the best conditions for the highest purity of IgY. With this operating parameters(flow rate in three zone and switching time), the purity of raffinate results in 98.39% from Aspen chromatography simulation. Most of the simulation reached steadystate within second recycle.

Discontinuous and continuous separation of the monomeric and dimeric forms of human bone morphogenetic protein-2 from renaturation batches

Bone morphogenetic protein-2 (BMP-2) is one of the most interesting of the approximately 14 BMPs which belong to the transforming-growth-factor-β (TGF-β) superfamily. BMP-2 induces bone formation and thus plays an important role as a pharmaceutical protein. Recently, rhBMP-2 has been produced in form of inactive inclusion bodies in Escherichia coli. After solubilization and renaturation the biologically active dimeric form of rhBMP-2 can be generated. However, inactive monomers of BMP-2 are also formed during the renaturation process which must be separated from the active dimeric BMP-2. The purpose of this paper is to present: (a) results of an experimental study of a chromatographic separation of the monomeric and dimeric forms; and (b) a concept for a continuous counter-current simulated moving bed (SMB) process. The capacity of heparin as stationary phase was estimated for different salt concentrations in the mobile phase. A simulation study of a three-zone SMB process was performed applying a two step salt gradient. The results reveal the potential of the process for the purification of the dimeric BMP-2.

Insulin Wave Dynamics in Size-Exclusion Simulated Moving Bed with Residence Time Control

In the application of simulated moving bed (SMB) technology to a pharmaceutical purification, the residence time of a product inside the SMB should be shortened, to prevent possible aggregation or denaturation. In addition, each key concentration wave should be confined in an appropriate zone to maintain high yield and high purity throughout the SMB operation. To achieve both goals, one must first understand clearly dynamic wave propagation phenomena in connection with solute residence time in the SMB. For this purpose, a series of transient column profiles in the tandem SMB for insulin purification are generated from computer simulations based on a detailed rate model. The column profiles show that the insulin molecules take a long time to reach the product port if they stay in the zone where the insulin wave is standing (or the standing zone). This leads to a long residence time. To shorten the insulin residence time, one can reduce the amount of insulin in the standing zone or modify the zone flow rates such that the insulin wave becomes focused or pinched. The former can be realized by a partial feeding strategy and the latter by a pinched wave design (PWD) method. The wave propagation phenomena for each case are shown using a series of insulin column profiles from the rate model simulations. Based on the understanding of the insulin wave dynamics, a three-zone SMB based on the PWD condition is proposed as the most effective strategy to reduce the residence time of insulin.

Three-Zone Simulated Moving Bed with Partial Feed and Selective Withdrawal

Three-zone simulated moving bed (SMB) systems are studied for binary separation within the linear range. Simulations were done by modifying the well-known Lapidus and Amundson dispersion model to include changing velocities and variable feed concentrations. Several different operations, total feed and withdrawal and partial feed and withdrawal, are tested and compared. The total operation is the traditional SMB operation, where feed or product are added or withdrawn continuously at a constant rate. The partial operations have variable port flow rates. For both, the three-zone SMB with one column per zone improves its productivity, desorbent efficiency, product purities, and recoveries. With the same total amount of adsorbent, the separation achieved in a three-zone SMB with 1 column/zone and partial feed and partial withdrawal was slightly better than the separation in a traditional four-zone SMB with 2 columns/zone.