Efficient simulation of chromatographic separation processes

This work presents the development and testing of an efficient, high resolution algorithm developed for the solution of equilibrium and non-equilibrium chromatographic problems as a means of simultaneously producing high fidelity predictions with a minimal increase in computational cost. The method involves the coupling of a high-order WENO scheme, adapted for use on non-uniform grids, with a piecewise adaptive grid (PAG) method to reduce runtime while accurately resolving the sharp gradients observed in the processes under investigation. Application of the method to a series of benchmark chromatographic test cases, within which an increasing number of components are included over short and long spatial domains and containing shocks, shows that the method is able to accurately resolve the discontinuities and that the use of the PAG method results in a reduction in the CPU runtime of up to 90%, without degradation of the solution, relative to an equivalent uniform grid

Efficient Simulation of Chromatographic Processes Using the Conservation Element/Solution Element Method

Chromatographic separation processes need efficient simulation methods, especially for nonlinear adsorption isotherms such as the Langmuir isotherms which imply the formation of concentration shocks. The focus of this paper is on the space–time conservation element/solution element (CE/SE) method. This is an explicit method for the solution of systems of partial differential equations. Numerical stability of this method is guaranteed when the Courant–Friedrichs–Lewy condition is satisfied. To investigate the accuracy and efficiency of this method, it is compared with the classical cell model, which corresponds to a first-order finite volume discretization using a method of lines approach (MOL). The evaluation is done for different models, including the ideal equilibrium model and a mass transfer model for different adsorption isotherms—including linear and nonlinear Langmuir isotherms—and for different chromatographic processes from single-column operation to more sophisticated simulated moving bed (SMB) processes for the separation of binary and ternary mixtures. The results clearly show that CE/SE outperforms MOL in terms of computational times for all considered cases, ranging from 11-fold for the case with linear isotherm to 350-fold for the most complicated case with ternary center-cut eight-zone SMB with Langmuir isotherms, and it could be successfully applied for the optimization and control studies of such processes

OUTLOOK FOR EMERGING TECHNOLOGIES IN SUGAR PROCESSING

Agribusiness,

Countercurrent chromatography in analytical chemistry (IUPAC technical report)

© 2009 IUPACCountercurrent chromatography (CCC) is a generic term covering all forms of liquid-liquid chromatography that use a support-free liquid stationary phase held in place by a simple centrifugal or complex centrifugal force field. Biphasic liquid systems are used with one liquid phase being the stationary phase and the other being the mobile phase. Although initiated almost 30 years ago, CCC lacked reliable columns. This is changing now, and the newly designed centrifuges appearing on the market make excellent CCC columns. This review focuses on the advantages of a liquid stationary phase and addresses the chromatographic theory of CCC. The main difference with classical liquid chromatography (LC) is the variable volume of the stationary phase. There are mainly two different ways to obtain a liquid stationary phase using centrifugal forces, the hydrostatic way and the hydrodynamic way. These two kinds of CCC columns are described and compared. The reported applications of CCC in analytical chemistry and comparison with other separation and enrichment methods show that the technique can be successfully used in the analysis of plants and other natural products, for the separation of biochemicals and pharmaceuticals, for the separation of alkaloids from medical herbs, in food analysis, etc. On the basis of the studies of the last two decades, recommendations are also given for the application of CCC in trace inorganic analysis and in radioanalytical chemistry

Ecodesign of Batch Processes: Optimal Design Strategies for Economic and Ecological Bioprocesses

This work deals with the multicriteria cost-environment design of multiproduct batch plants, where the design variables are the equipment item sizes as well as the operating conditions. The case study is a multiproduct batch plant for the production of four recombinant proteins. Given the important combinatorial aspect of the problem, the approach used consists in coupling a stochastic algorithm, indeed a Genetic Algorithm (GA) with a Discrete Event Simulator (DES). To take into account the conflicting situations that may be encountered at the earliest stage of batch plant design, i.e. compromise situations between cost and environmental consideration, a Multicriteria Genetic Algorithm (MUGA) was developed with a Pareto optimal ranking method. The results show how the methodology can be used to find a range of trade-off solutions for optimizing batch plant design

Geochemical Consequences of Melt Percolation: The Upper Mantle as a Chromatographic Column

As magmas rise toward the surface, they traverse regions of the mantle and crust with which they are not in equilibrium; to the extent that time and the intimacy of their physical contact permit, the melts and country rocks will interact chemically. We have modeled aspects of these chemical interactions in terms of ion-exchange processes similar to those operating in simple chromatographic columns. The implications for trace element systematics are straightforward: the composition of melt emerging from the top of the column evolves from close to that of the incipient melt of the column matrix toward that of the melt introduced into the base of the column. The rate of evolution is faster in the incompatible than the compatible elements and, as a result, the abundance ratios of elements of different compatibilities can vary considerably with time. If diffusion and other dispersive processes in the melt are negligible and if exchange between melt and solid rock is rapid, extreme fractionations may occur, and the change from initial to final concentration for each element can be through an abrupt concentration front. Integration and mixing of the column output in a magma chamber or dispersive processes within the column, in particular the incomplete equilibration between matrix and fluid due to the slow diffusion in the solid phases, may lead to diffuse fronts and smooth trace element abundance patterns in the column output. If the matrix material is not replenished, the chromatographic process is a transient phenomenon. In some geological situations (e.g., under island arcs and oceanic islands), fresh matrix may be fed continuously into the column, leading to the evolution of a steady state. Aspects of the geochemistry of ultramafic rocks, island arc lavas, and comagmatic alkaline and tholeiitic magmas may be explained by the operation of chromatographic columns

Separation of nadolol racemates by high pH reversed-phase fixed-bed and simulated moving bed chromatography

The separation of nadolol racemates under high pH reversed-phase using both the fixed-bed (FB) and the simulated moving bed (SMB) preparative chromatographic techniques is reported after the previous published work [1] where the Waters XBridge C18 adsorbent and an ethanol:water:diethylamine solvent mixture were validated to allow the separation of the multicomponent feed mixture composed by four nadolol stereoisomers into two pure racemates (two pairs of enantiomers). In this work, the experimental preparative separations using one commercial fixed-bed preparative HPLC Azura system equipped with one sole column of preparative dimensions (30 mm ID × 250 mm L) and one labscale SMB apparatus (the FlexSMB-LSRE pilot unit) equipped with six semi-preparative columns (19 mm ID × 100 mm L) are presented. Both systems use the Waters XBridge C18 adsorbent of 10 μm particle diameter. The screening of the mobile phase composition elected the 30:70:0.1 (v/v/v) ethanol:water:diethylamine solvent mixture to perform both FB and SMB preparative operations. A large set of experimental, modelling and simulation results are presented, including pulses, measurement and modelling of the adsorption equilibrium isotherms, and its validation through breakthroughs measurements. The modelling and simulation steps allowed the prediction and the optimization of both the FB and SMB operating conditions. For FB, using a feed concentration of 9 g/L of an equimolar mixture of the two nadolol racemates, both were recovered almost pure (at least 99.9 %), with a global system productivity of 3.06 gfeed/(Lbed.hr) and a solvent consumption of 4.21 Lsolvent/gfeed. For SMB, the pilot unit’s pressure drops limits imposed a maximum internal flow-rate of only 5 mL/min and, for a nadolol feed concentration of 2 g/L, both racemates were recovered 100 % pure, with a system productivity of 0.13 gfeed/(Lbed.hr) and a solvent consumption of 6.19 Lsolvent/gfeed. Additional simulation results showed that a SMB preparative unit can perform the 9 g/L nadolol racemate separation with a system productivity of 3.61 gfeed/(Lbed.hr) and a solvent consumption of only 1.95 Lsolvent/gfeed using the same average internal flow-rate as in FB operation. Even better SMB productivities can still be obtained using the same feed or solvent flow-rates as in FB operation if the internal SMB flow-rates are allowed and not limited by the system pressure drop. The experimental results presented in this work validate the strategy of separating a four nadolol stereoisomers mixture into two pure nadolol racemates, each one composed by a pair of nadolol enantiomers, using an achiral C18 adsorbent through FB and SMB chromatographic techniques. Each nadolol racemate can later be purified into pure nadolol stereoisomers using standard binary chiral FB and SMB chromatography. In this way, this works introduces a real and experimental solution for the complete multicomponent preparative separation of the four nadolol stereoisomers.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES (PIDDAC) to CIMO (UIDB/00690/2020 and UIDP/00690/ 2020) and SusTEC (LA/P/0007/2020). National funding by FCT, Foundation for Science and Technology, through the individual research grant (SFRH/BD/137966/2018) of Rami S. Arafah is also acknowledged.info:eu-repo/semantics/publishedVersio

Towards continuous biomanufacturing a computational approach for the intensification of monoclonal antibody production

Current industrial trends encourage the development of sustainable, environmentally friendly processes with reduced energy and raw material consumption. Meanwhile, the increasing market demand as well as the tight regulations in product quality, necessitate efficient operating procedures that guarantee products of high purity. In this direction, process intensification via continuous operation paves the way for the development of novel, eco-friendly processes, characterized by higher productivity compared to batch (Nicoud, 2014). The shift towards continuous operation could advance the market of high value biologics, such as monoclonal antibodies (mAbs), as it would lead to shorter production times, decreased costs, as well as significantly less energy consumption (Konstantinov and Cooney, 2015, Xenopoulos, 2015). In particular, mAb production comprises two main steps: the culturing of the cells (upstream) and the purification of the targeted product (downstream). Both processes are highly complex and their performance depends on various parameters. In particular, the efficiency of the upstream depends highly on cell growth and the longevity of the culture, while product quality can be jeopardized in case the culture is not terminated timely. Similarly, downstream processing, whose main step is the chromatographic separation, relies highly on the setup configuration, as well as on the composition of the upstream mixture. Therefore, it is necessary to understand and optimize both processes prior to their integration. In this direction, the design of intelligent computational tools becomes eminent. Such tools can form a solid basis for the: (i) execution of cost-free comparisons of various operating strategies, (ii) design of optimal operation profiles and (iii) development of advanced, intelligent control systems that can maintain the process under optimal operation, rejecting disturbances. In this context, this work focuses on the development of advanced computational tools for the improvement of the performance of: (a) chromatographic separation processes and (b) cell culture systems, following the systematic PAROC framework and software platform (Pistikopoulos et al., 2015). In particular we develop model-based controllers for single- and multi-column chromatographic setups based on the operating principles of an industrially relevant separation process. The presented strategies are immunized against variations in the feed stream and can successfully compensate for time delays caused due to the column residence time. Issues regarding the points of integration in multi-column systems are also discussed. Moreover, we design and test in silico model-based control strategies for a cell culture system, aiming to increase the culture productivity and drive the system towards continuous operation. Challenges and potential solutions for the seamless integration of the examined bioprocess are also investigated at the end of this thesis.Open Acces

Optimization of Chiral Separation of Nadolol by Simulated Moving Bed Technology

Simulated Moving Bed (SMB) technology has gained increasing attention as one of the most powerful techniques for chromatographic separations due to its cost-effectiveness and efficiency. Application of SMB technology is especially important in the pharmaceutical industry for production of enantiopure drugs, as required under strict FDA regulations, to avoid possible adverse effects of racemic drugs. In this study, the performance of the SMB process in separation of racemic nadolol on a perphenyl carbamoylated beta cyclodextrin (β-CD) stationary phase was investigated. The equilibrium dispersive model coupled with bi-Langmuir adsorption isotherm and lumped kinetic approximation, constitute the mathematical model used to simulate the dynamic behavior of SMB. Multi-objective optimization was carried out using a robust state-of-the-art optimization technique, non-dominated sorting genetic algorithm (NSGA). Two optimization problems were solved to simultaneously maximize productivity and purity of the product and minimize consumption of desorbent. The generated Pareto optimal solutions showed that selection of operating conditions can significantly affects the performance of SMB to meet the desired objectives