Continuous prediction technique for fast determination of cyclic steady state in simulated moving bed process

In the simulation of cyclic processes, such as simulated moving bed (SMB), the system should be equilibrated to reach a cyclic steady state (CSS) before evaluating the process performance. However, the conventional method of successive substitution is quite time-consuming. In this work, a continuous predicting method (CPM) is developed for fast determination of CSS in SMB. In CPM, the direct prediction of state variable at CSS and solving model equation are conducted alternately until CSS is reached. In order to give a guideline for the selection of the acceleration factor, CPM is applied on SMB process for enantio separation of 1,1'-bi-2-naphtol racemate and with the optimized acceleration factor, 59% of computation time saved compared with successive substitution. In addition, this method is further successfully used in a sugar separation process. Given its efficiency and simplicity, this method could provide a useful tool for SMB simulations

A Comprehensive Study Of Esterification Of Free Fatty Acid To Biodiesel In a Simulated Moving Bed System

Simulated Moving Bed (SMB) systems are used for separations that are difficult using traditional separation techniques. Due to the advantage of adsorption-based chromatographic separation, SMB has shown promising application in petrochemical and sugar industries, and of late, for chiral drug separations. In recent years, the concept of integration of reaction and in-situ separation in a single unit has achieved considerable attention. The simulated moving bed reactor (SMBR) couples both these unit operations bringing down the operation costs while improving the process performance, particularly for products that require mild operating conditions. However, its application has been limited due to complexity of the SMBR process. Hence, to successfully implement a reaction in SMB, a detailed understanding of the design and operating conditions of the SMBR corresponding to that particular reaction process is necessary. Biodiesel has emerged has a viable alternative to petroleum-based diesel as a renewable energy source in recent years. Biodiesel can be produced by esterification of free fatty acids (present in large amounts in waste oil) with alcohol. The reaction is equilibrium-limited, and hence, to achieve high purity, additional purification steps increases the production cost. Therefore, combining reaction and separation in SMBR to produce high purity biodiesel is quite promising in terms of bringing down the production cost. In this work, the reversible esterification reaction of oleic acid with methanol catalyzed by Amberlyst 15 resin to form methyl oleate (biodiesel) in SMBR has been investigated both theoretically and experimentally. First, the adsorption and kinetic constants were determined for the biodiesel synthesis reaction by performing experiments in a single column packed with Amberlyst 15, which acts as both adsorbent and catalyst. Thereafter, a rigorous model was used to describe the dynamic behaviour of multi-column SMBR followed by experimental verification of the mathematical model. Sensitivity analysis is done to determine robustness of the model. Finally, a few simple multi-objective optimization problems were solved that included both existing and design-stage SMBRs using non-dominated sorting genetic algorithm (NSGA). Pareto-optimal solutions were obtained in both cases, and moreover, it was found that the performance of the SMBR could be improved significantly under optimal operating conditions

Advances in simulated moving bed : new operating modes : new design methodologies and product (FlexSMB-LSRE) development

Tese de doutoramento. Engenharia Química e Biológica. Faculdade de Engenharia. Universidade do Porto. 200

Towards Intensified Protein Refolding and Purification on Size Exlusion Chromatography: Fundamental Studies and Mathematical Modelling

For industrial recombinant-protein processes, protein refolding and purification are crucial steps towards the recovery of considerable numbers of active and safe therapeutic products. In this thesis, intensification strategies for protein refolding and purification processes are explored. Development of an intensified process aims at simultaneous optimization of process performance indicators, namely: refolding yield, product purity, volumetric productivity and solvent consumption which in turn decrease the cost and time constraints to market. The first strategy investigated related to multivariable experimental work using size exclusion chromatography (SEC) as a refolding method and a denatured/reduced model protein (lysozyme). SEC was selected due to its potential for refolding of higher concentrations of protein compared to conventional refolding methods used currently in industry. The investigated variables were protein loading concentration, refolding buffer composition including pH, sodium chloride salt and ʟ-arginine, aggregation prevention additive, concentrations. The interplay of these process variables was studied and it was shown when ʟ-arginine is used, over the experimental space, the effects of pH and protein loading concentration on refolding yield are insignificant. This observation introduced the possibility of manipulating pH in a wider range without concerns for protein aggregation; for instance, to adjust the redox potential of the buffer without the need for costly redox couple chemicals to assist reformation of disulfide bridges in oxidative refolding of the protein. The results also provide more experimental evidence on the mechanism of aggregation prevention by ʟ-arginine. Secondly an experimentally-verified model of oxidative protein refolding on SEC was developed, with the goal of high-throughput process screening and optimization using the aforementioned model. Model development involved exploration of methods to find characteristic information on short-lived refolding kinetic species and lysozyme oxidative refolding kinetic schemes and constants under the two studied refolding environments, namely with and without ʟ-arginine additive. It was shown that ʟ-arginine prevents aggregation without considerable impact on the kinetics of lysozyme oxidative refolding. Finally, SEC in a multi-column continuous simulated moving bed configuration (SMB-SEC) was evaluated to fully exploit the potential of SEC for intensified protein refolding and purification. This configuration offers several advantages compared to single-column operation, including increased productivity per unit mass of solid phase, lower solvent consumption, and less diluted products, provided that operation parameters are screened and tuned for simultaneous optimization of process performance indicators. In this phase of the project, the effect of scale-up was predicted and considered for modifying and utilizing single-column model towards design/operation of a SMB-SEC. This thesis presents a framework for protein refolding and purification process development and optimization, including reduced cost of chemicals, improving the refolding yield, high-throughput measurements of parameters and finding a suitable reaction scheme of refolding and aggregation for mathematical model development applicable to both single-column and multi-column continuous operations, and defining appropriate process performance indicators for optimized operation of SMB-SEC

A Comprehensive Study of Sequential Simulated Moving Bed: Purification of Xylo-oligosaccharides and fructose-glucose

Chromatographic separation is a promising alternative for separation and purification of sugars in industry. Simulated moving bed (SMB) technique has been proven as an efficient chromatographic separation method due to its enhanced productivity and purity, reduced solvent consumption, convenient operating control, and improved separation performance for some systems with low resolution and selectivity. The sequential simulated moving bed (SSMB) is a modification of the conventional SMB process, which currently has some applications for sugar separation due to its low solvent consumption. This work mainly investigates the design strategy of the innovative SSMB process and explore its advantages and disadvantages over the SMB process based on the xylo-oligosaccharides (XOSs) and fructose-glucose systems. SSMB separation of XOSs, a functional food additive in the form of a oligomeric saccharide, was firstly conducted. DOWEX MONOSPHERETM 99/310 resin ionized with K+, which has better selectivity compared with Ca2+ and Na+ was used as the stationary phase.Breakthrough experiments showed that XOSs and the two major industrial impurities, xylose and arabinose, all exhibit linear isotherms. Transport-dispersive (TD) model parameters were determined by pulse experiments carried out at various flowrates. Finally, both the averaged and individual parameters of XOSs and XOS2-XOS7 were obtained. Lab-scale SSMB experiments and the corresponding simulations were carried out to validate the acquired TD model parameters and adsorption isotherms. After that, in order to investigate the optimal operating conditions of this process, the multi-objective optimizations were carried out for three cases with various objectives and constraints. It was found that, for a given SSMB unit, there exist a pareto curve for simultaneous maximization of purity and unit throughput. The flowrate ratios (m values), however, exhibit some trends that are different from those of conventional SMB and cannot be explained by the direct use of Triangle Theory with averaged m values. According to the literature, the fructose-glucose system is representative and have linear isotherms over a wide concentration range, which makes it an excellent example system to conduct some basic analysis and performance prediction. Therefore, the multi-objective optimization of SMB and SSMB processes was conducted and compared based on the fructose-glucose system. The results show that the solvent consumption of SSMB is always less than that of SMB unit

Design of Mixed-Solvent Extraction and Size-Exclusion Simulated Moving Bed Chromatography to Recover Valuable Compounds from Electronic Waste

More than one million tons of polycarbonates and over 500,000 tons of flame retardants are consigned to landfills each year in the form of waste electrical and electronic equipment. Electronic waste is the fasting growing waste steam at a rate of 3-5% per year. Two separation processes are developed to efficiently recover these valuable compounds

Chiral Separation of Racemic Mandelic Acid by the Coupling Crystallization Process and Simulated Moving Bed Technology

Chirality is a major concern in the modern pharmaceutical, food and agricultural industries. The importance of enantiopure drugs has risen dramatically in recent years due to FDA regulations requiring that all chiral bioactive molecules must be isolated and tested for the efficacy and safety, and have to be as pure as possible containing a single pure enantiomer. There are essentially three strategies that can be applied to obtain single pure isomers: (a) extraction from plants and animal materials (b) enantio-selective asymmetric synthesis so that only one isomer is formed in the first place, or (c) making a racemate and finding a method for separating the enantiomers. Only few enantiomers exist in nature and most of them are racemates. A highly efficient chiral asymmetric synthesis route would be the ideal situation, but it usually takes about 10-15 years to develop a synthesis recipe. Hence, the best strategy would be to synthesize the drug in racemate form and separate the isomers to produce single pure enantiomer. Among the variety of enantioseparation methods, chromatography and crystallization are the most dominant methods for the recovery of pure enantiomers. However, both methods have limitations. Crystallization cannot obtain enantiopure enantiomers from the racemic compound directly. In SMB, solvent consumption increases exponentially if desired purity requirement is close to 100%. In this work, the coupling of SMB for enrichment followed by direct crystallization is applied for the chiral resolution to circumvent limitations of each method. In order to take advantage of both the processes, SMB chromatography is used for partial enrichment thereby reducing solvent consumption followed by direct crystallization to obtain 100% pure enantiomers. Here, the chiral resolution of mandelic acid as racemic compound was considered to investigate the performance of the hybrid SMB-crystallization process theoretically as well as experimentally. The solubility and metastable zone limit of (R,S)-MA and (R)-MA in water and the crystallization kinetics parameters of (R,S)-mandelic acid and (R)-mandelic acid by optimization of the crystallization model based on the necessary experimental data collected in unseeded cooling batch crystallizers were determined. For the SMB part, the choice of mobile phase and determination of binary competitive equilibrium isotherms parameters of (R,S)-Mandelic acid and the experimental and modeling studies of SMB process have also been accomplished