The Experts below are selected from a list of 4197 Experts worldwide ranked by ideXlab platform
Greg Foley - One of the best experts on this subject based on the ideXlab platform.
-
Class and Homework Problems: The Lambert W function in ultrafiltration and Diafiltration
Chemical engineering education, 2016Co-Authors: Greg FoleyAbstract:Novel analytical solutions based on the Lambert W function for two problems in ultrafiltration and Diafiltration are described. Example problems, suitable for incorporation into an introductory module in unit operations, membrane processing or numerical methods are provided in each case.
-
optimal feeding strategy of Diafiltration buffer in batch membrane processes
Journal of Membrane Science, 2012Co-Authors: Radoslav Paulen, Zoltan Kovacs, Miroslav Fikar, Greg Foley, Peter CzermakAbstract:This work addresses the optimal control strategy of Diafiltration buffer utilisation in discontinuous membrane processes that are designed to fulfil the twin aims of concentration and fractionation. The problem of optimal process operation is formulated using a general membrane response model that encounters concentration-dependent flux and rejections. We consider two problems, operation time minimisation and diluant consumption minimisation, and we apply theory of optimal control and derive necessary conditions of optimality. Through selected case studies from the literature, we demonstrate how to apply the proposed methodology to determine optimal time-dependent wash-water feeding policy. The analytical results are confirmed by numerical computations, using numerical methods of dynamic optimisation. The presented methodology allows decision makers to analyse suboptimality of conventional Diafiltration strategies in terms of processing time and diluant consumption. Results show that depending on the complexity of the membrane response model, it may be attractive to implement optimal trajectory.
-
minimizing the process time for ultrafiltration Diafiltration under gel polarization conditions
Journal of Membrane Science, 2011Co-Authors: Radoslav Paulen, Zoltan Kovacs, Miroslav Fikar, Peter Czermak, Greg FoleyAbstract:Abstract This study examines a generalized ultrafiltration/Diafiltration process that is designed to reduce the initial volume of a given process liqueur and to eliminate impurities from the product solution. This theoretical investigation focuses on applications where the permeate flux is given by the gel polarization model. The goal of this paper is to use optimal control theory to determine optimal time-varying diluant addition that minimizes treatment time. We propose a Diafiltration model in a dimensionless form with normalized model equations in order to determine general features of optimal diluant utilization strategy. Based on the model, we formulate the optimal control problem and apply the theory of optimal control exploiting the Pontryagin’s minimum principle. We confirm the analytical results by numerical computations using numerical methods of dynamic optimization. We prove that optimal control strategy is to perform a constant-volume Diafiltration step at optimal macro-solute concentration that guarantees maximal removal of micro-solute at any time instant. This constant-volume Diafiltration step is preceded and followed by optional ultrafiltration or pure dilution steps that force the concentrations at first to arrive to the optimal macro-solute concentration and at last to arrive to the desired final concentrations. Finally, we provide practical optimization diagrams that allow decision makers to determine the optimal diluant control of a given separation task.
-
Minimizing the process time for ultrafiltration/Diafiltration under gel polarization conditions
Journal of Membrane Science, 2011Co-Authors: Radoslav Paulen, Zoltan Kovacs, Miroslav Fikar, Greg Foley, Peter CzermakAbstract:Abstract This study examines a generalized ultrafiltration/Diafiltration process that is designed to reduce the initial volume of a given process liqueur and to eliminate impurities from the product solution. This theoretical investigation focuses on applications where the permeate flux is given by the gel polarization model. The goal of this paper is to use optimal control theory to determine optimal time-varying diluant addition that minimizes treatment time. We propose a Diafiltration model in a dimensionless form with normalized model equations in order to determine general features of optimal diluant utilization strategy. Based on the model, we formulate the optimal control problem and apply the theory of optimal control exploiting the Pontryagin’s minimum principle. We confirm the analytical results by numerical computations using numerical methods of dynamic optimization. We prove that optimal control strategy is to perform a constant-volume Diafiltration step at optimal macro-solute concentration that guarantees maximal removal of micro-solute at any time instant. This constant-volume Diafiltration step is preceded and followed by optional ultrafiltration or pure dilution steps that force the concentrations at first to arrive to the optimal macro-solute concentration and at last to arrive to the desired final concentrations. Finally, we provide practical optimization diagrams that allow decision makers to determine the optimal diluant control of a given separation task.
-
evaluation of variable volume Diafiltration processes using the logarithmic integral
Desalination and Water Treatment, 2011Co-Authors: Greg FoleyAbstract:The minimum process times for ultrafiltration with constant volume Diafiltration (UFCVD) and ultrafiltration with variable volume Diafiltration (UFVVD) are compared for limiting flux conditions. Using the series definition of the Logarithmic Integral, the optimum concentration to begin VVD is found by numerical solution of a non-linear algebraic equation. This equation is used to establish a criterion for UFVVD to be faster than UFCVD. Calculations indicate that this criterion is never satisfied and thus UFVVD can never be done more rapidly than UFCVD.
Andrew L Zydney - One of the best experts on this subject based on the ideXlab platform.
-
purification of a conjugated polysaccharide vaccine using tangential flow Diafiltration
Biotechnology and Bioengineering, 2019Co-Authors: Parinaz Emami, Seyed Pouria Motevalian, Erin Pepin, Andrew L ZydneyAbstract:: Conjugated vaccines prepared from the capsular polysaccharide of Streptococcus pneumoniae can provide immunization against invasive pneumococcal disease, meningitis, and otitis media. One of the critical steps in the production of these vaccines is the removal of free (unreacted) polysaccharides from the protein-polysaccharide conjugate. Experimental studies were performed to evaluate the effects of membrane pore size, filtrate flux, and solution conditions on the transmission of both the conjugate and free polysaccharide through different ultrafiltration membranes. Conjugate purification was done using Diafiltration performed in a linearly-scalable tangential flow filtration cassette. More than 98% of the free polysaccharide was removed within a 5-diavolume Diafiltration process, which is a significant improvement over previously reported results for purification of similar conjugated vaccines. These results clearly demonstrate the opportunities for using ultrafiltration/Diafiltration for the final purification of conjugated vaccine products.
-
countercurrent staged Diafiltration for formulation of high value proteins
Biotechnology and Bioengineering, 2018Co-Authors: Anirudh M K Nambiar, Ying Li, Andrew L ZydneyAbstract:A number of groups have studied the application of continuous bioreactors and continuous chromatographic systems as part of efforts to develop an integrated continuous biomanufacturing process. The objective of this study was to examine the feasibility of using a countercurrent staged Diafiltration process for continuous protein formulation with reduced buffer requirements. Experiments were performed using a polyclonal immunoglobulin (IgG) with CadenceTM Inline Concentrators. Model equations were developed for the product yield, impurity removal, and buffer requirements as a function of the number of stages and the stage conversion (ratio of permeate to feed flow rate). Data from a countercurrent two-stage system were in excellent agreement with model calculations, demonstrating the potential of using countercurrent staged Diafiltration for protein formulation. Model simulations demonstrated the importance of the countercurrent staging on both the extent of buffer exchange and the amount of buffer required per kg of formulated product. The staged Diafiltration process not only provides for continuous buffer exchange, it could also provide significant reductions in the number of pump passes while providing opportunities for reduced buffer requirements. This article is protected by copyright. All rights reserved
-
ph variations during Diafiltration due to buffer nonidealities
Biotechnology Progress, 2017Co-Authors: Youngbin Baek, Deyu Yang, Nripen Singh, Abhiram Arunkumar, Sanchayita Ghose, Zheng Jian Li, Andrew L ZydneyAbstract:Diafiltration is used for final formulation of essentially all biotherapeutics. Several studies have demonstrated that buffer/excipient concentrations in the final diafiltered product can be different than that in the Diafiltration buffer due to interactions between buffer species and the protein product. However, recent work in our lab has shown variations in solution pH that are largely independent of the protein concentration during the first few diavolumes. Our hypothesis is that these pH variations are due to non-idealities in the acid-base equilibrium coefficient. A model was developed for the Diafiltration process accounting for the ionic strength dependence of the pKa. Experimental results obtained using phosphate and histidine buffers were in excellent agreement with model predictions. A decrease in ionic strength leads to an increase in the pKa for the phosphate buffer, causing a shift in the solution pH, even under conditions where the initial feed and the Diafiltration buffer are at the same pH. This effect could be eliminated by matching the ionic strength of the feed and Diafiltration buffer. The experimental data and model provide new insights into the factors controlling the pH profile during Diafiltration processes. This article is protected by copyright. All rights reserved.
-
small molecule clearance in ultrafiltration Diafiltration in relation to protein interactions study of citrate binding to a fab
Biotechnology and Bioengineering, 2009Co-Authors: Chithkala Harinarayan, Andrew L Zydney, K Skidmore, R Van ReisAbstract:Ultrafiltration/Diafiltration (UFDF) is commonly utilized in the purification of recombinant proteins to concentrate and buffer exchange the product. It is often the final step in the purification process, placing the protein in its final formulation and clearing small molecules introduced in upstream purification steps. This article presents a case study of reduced small molecule clearance in ultrafiltration/Diafiltration of an antigen-binding fragment of a monoclonal antibody. Citrate, a commonly utilized small molecule in downstream processes, is shown to have reduced clearance due to specific interactions with the protein product. The study presents process solutions and utilizes a simple model to characterize clearance of small molecules which exhibit interactions with product protein.
-
Small molecule clearance in ultrafiltration/Diafiltration in relation to protein interactions:Study of citrate binding to a Fab.
Biotechnology and Bioengineering, 2009Co-Authors: Chithkala Harinarayan, Andrew L Zydney, K Skidmore, R Van ReisAbstract:Ultrafiltration/Diafiltration (UFDF) is commonly utilized in the purification of recombinant proteins to concentrate and buffer exchange the product. It is often the final step in the purification process, placing the protein in its final formulation and clearing small molecules introduced in upstream purification steps. This article presents a case study of reduced small molecule clearance in ultrafiltration/Diafiltration of an antigen-binding fragment of a monoclonal antibody. Citrate, a commonly utilized small molecule in downstream processes, is shown to have reduced clearance due to specific interactions with the protein product. The study presents process solutions and utilizes a simple model to characterize clearance of small molecules which exhibit interactions with product protein.
Zoltan Kovacs - One of the best experts on this subject based on the ideXlab platform.
-
time optimal operation of multi component batch Diafiltration
Computers & Chemical Engineering, 2015Co-Authors: Martin Jelemenský, Zoltan Kovacs, Miroslav Fikar, Radoslav PaulenAbstract:Abstract We study the minimum-time operation of batch multi-component Diafiltration processes. We employ the technique of Pontryagin's minimum principle to derive the candidates for an optimal operation. The optimal operation is defined as a state-feedback strategy. Simulations and numerical optimizations are applied to confirm the optimality of the proposed time-optimal operation. Obtained results are evaluated on two case studies, a typical multi-component Diafiltration processes. Standard operational approaches are compared to the optimal operation and the resulting improvements show attractivity of the proposed approach.
-
economically optimal batch Diafiltration via analytical multi objective optimal control
Journal of Process Control, 2015Co-Authors: Zoltan Kovacs, Martin Jelemenský, Radoslav Paulen, Miroslav FikarAbstract:Abstract This paper studies the problem of economically oriented optimal operation of batch membrane Diafiltration processes that are designed to concentrate the valuable components of the solution and to purge the impurities from it. We consider a complex economical objective that accounts for the total operational costs comprising a cost of consumed diluant, costs related to duration of processing, and a cost of product loss. The optimization problem is formulated as a multi-objective optimal control problem in order to investigate the impact of operational cost factors on optimal operation policy. This is achieved thanks to the use of the analytical approach that exploits Pontryagin's minimum principle. We show that the economically optimal control strategy is to carry out an operation involving saturated (bang-bang or constraint-tracking) control modes and a singular arc. For the most common cases of Diafiltration problems, it turns out that the switching of the consecutive control modes can be realized in the state feedback fashion, i.e. the entire optimal operation is defined analytically in the space of process states. We demonstrate the applicability of the presented approach and we illustrate achievable benefits, over traditional control methods for the batch Diafiltration processes, on two case studies taken from the literature.
-
time optimal control of batch multi component Diafiltration processes
Computer-aided chemical engineering, 2014Co-Authors: Martin Jelemenský, Zoltan Kovacs, Miroslav Fikar, Radoslav PaulenAbstract:Abstract This paper studies the time-optimal operation of batch multi-component Diafiltration processes. We employ the technique of Pontryagin’s minimum principle to derive the candidates for optimal operation. Simulations and numerical optimizations are applied to define the time-optimal solution. The obtained results are evaluated on a case study, a typical multi-component Diafiltration process. A comparison is provided between standard operational approaches and the newly derived optimal one.
-
optimal balancing of temporal and buffer costs for ultrafiltration Diafiltration processes under limiting flux conditions
Journal of Membrane Science, 2013Co-Authors: Zoltan Kovacs, Miroslav Fikar, Martin Jelemenský, Radoslav PaulenAbstract:Abstract This paper studies the problem of economically oriented optimal operation of an ultrafiltration/Diafiltration process that is designed to reduce the initial volume of a given process liquor and to eliminate impurities from the product solution in a batch setup. This theoretical investigation focuses on applications where the permeate flux is given by the well-known limiting flux model and the rejections of micro-solute and macro-solute are assumed to be zero and one, respectively. Unlike previous approaches to the problem, we consider a complex economical objective that accounts for the total operational costs involving both the cost of consumed diluant and processing time-related costs. The optimization problem is formulated as a multi-objective optimal control problem and it is solved using the analytical approach that exploits Pontryagin's minimum principle. We prove that economically optimal control strategy is to perform a constant-volume Diafiltration step at a given, optimal macro-solute concentration. This constant-volume Diafiltration step is preceded and followed by ultrafiltration or pure dilution steps that force the concentrations at first to arrive to the optimal macro-solute concentration and at last to arrive to the desired final concentrations. By taking into account the unit prices of both processing time and utilized diluant, we provide a practical algebraic formula that allows decision makers to evaluate the optimal starting point of the constant-volume Diafiltration step and to adapt it when considered prices change. Finally, we demonstrate the applicability and achievable benefit of the here presented approach on an industrial-scale case study using literature data.
-
optimal feeding strategy of Diafiltration buffer in batch membrane processes
Journal of Membrane Science, 2012Co-Authors: Radoslav Paulen, Zoltan Kovacs, Miroslav Fikar, Greg Foley, Peter CzermakAbstract:This work addresses the optimal control strategy of Diafiltration buffer utilisation in discontinuous membrane processes that are designed to fulfil the twin aims of concentration and fractionation. The problem of optimal process operation is formulated using a general membrane response model that encounters concentration-dependent flux and rejections. We consider two problems, operation time minimisation and diluant consumption minimisation, and we apply theory of optimal control and derive necessary conditions of optimality. Through selected case studies from the literature, we demonstrate how to apply the proposed methodology to determine optimal time-dependent wash-water feeding policy. The analytical results are confirmed by numerical computations, using numerical methods of dynamic optimisation. The presented methodology allows decision makers to analyse suboptimality of conventional Diafiltration strategies in terms of processing time and diluant consumption. Results show that depending on the complexity of the membrane response model, it may be attractive to implement optimal trajectory.
Radoslav Paulen - One of the best experts on this subject based on the ideXlab platform.
-
time optimal operation of multi component batch Diafiltration
Computers & Chemical Engineering, 2015Co-Authors: Martin Jelemenský, Zoltan Kovacs, Miroslav Fikar, Radoslav PaulenAbstract:Abstract We study the minimum-time operation of batch multi-component Diafiltration processes. We employ the technique of Pontryagin's minimum principle to derive the candidates for an optimal operation. The optimal operation is defined as a state-feedback strategy. Simulations and numerical optimizations are applied to confirm the optimality of the proposed time-optimal operation. Obtained results are evaluated on two case studies, a typical multi-component Diafiltration processes. Standard operational approaches are compared to the optimal operation and the resulting improvements show attractivity of the proposed approach.
-
Multi-objective optimization of batch dialfiltration processes in the presence of membrane fouling
2015 20th International Conference on Process Control (PC), 2015Co-Authors: Martin Jelemenský, Miroslav Fikar, Ayush Sharma, Radoslav PaulenAbstract:This paper deals with a multi-objective optimization of a general batch Diafiltration process in the presence of fouling. Fouling, as one of the major problems in the membrane separation process, causes the decrease in the membrane area and thus the decrease in the filtration rate. The optimization problem considers a weighted combination of objectives for minimum-time and minimum-diluant operation. We apply numerical (orthogonal collocation) and analytical (Pontryagins minimum principle) methods to obtain the optimal operation of Diafiltration process when fouling is considered. A case study from literature highlights the properties and economical benefits of the optimal operation.
-
economically optimal batch Diafiltration via analytical multi objective optimal control
Journal of Process Control, 2015Co-Authors: Zoltan Kovacs, Martin Jelemenský, Radoslav Paulen, Miroslav FikarAbstract:Abstract This paper studies the problem of economically oriented optimal operation of batch membrane Diafiltration processes that are designed to concentrate the valuable components of the solution and to purge the impurities from it. We consider a complex economical objective that accounts for the total operational costs comprising a cost of consumed diluant, costs related to duration of processing, and a cost of product loss. The optimization problem is formulated as a multi-objective optimal control problem in order to investigate the impact of operational cost factors on optimal operation policy. This is achieved thanks to the use of the analytical approach that exploits Pontryagin's minimum principle. We show that the economically optimal control strategy is to carry out an operation involving saturated (bang-bang or constraint-tracking) control modes and a singular arc. For the most common cases of Diafiltration problems, it turns out that the switching of the consecutive control modes can be realized in the state feedback fashion, i.e. the entire optimal operation is defined analytically in the space of process states. We demonstrate the applicability of the presented approach and we illustrate achievable benefits, over traditional control methods for the batch Diafiltration processes, on two case studies taken from the literature.
-
time optimal control of batch multi component Diafiltration processes
Computer-aided chemical engineering, 2014Co-Authors: Martin Jelemenský, Zoltan Kovacs, Miroslav Fikar, Radoslav PaulenAbstract:Abstract This paper studies the time-optimal operation of batch multi-component Diafiltration processes. We employ the technique of Pontryagin’s minimum principle to derive the candidates for optimal operation. Simulations and numerical optimizations are applied to define the time-optimal solution. The obtained results are evaluated on a case study, a typical multi-component Diafiltration process. A comparison is provided between standard operational approaches and the newly derived optimal one.
-
optimal balancing of temporal and buffer costs for ultrafiltration Diafiltration processes under limiting flux conditions
Journal of Membrane Science, 2013Co-Authors: Zoltan Kovacs, Miroslav Fikar, Martin Jelemenský, Radoslav PaulenAbstract:Abstract This paper studies the problem of economically oriented optimal operation of an ultrafiltration/Diafiltration process that is designed to reduce the initial volume of a given process liquor and to eliminate impurities from the product solution in a batch setup. This theoretical investigation focuses on applications where the permeate flux is given by the well-known limiting flux model and the rejections of micro-solute and macro-solute are assumed to be zero and one, respectively. Unlike previous approaches to the problem, we consider a complex economical objective that accounts for the total operational costs involving both the cost of consumed diluant and processing time-related costs. The optimization problem is formulated as a multi-objective optimal control problem and it is solved using the analytical approach that exploits Pontryagin's minimum principle. We prove that economically optimal control strategy is to perform a constant-volume Diafiltration step at a given, optimal macro-solute concentration. This constant-volume Diafiltration step is preceded and followed by ultrafiltration or pure dilution steps that force the concentrations at first to arrive to the optimal macro-solute concentration and at last to arrive to the desired final concentrations. By taking into account the unit prices of both processing time and utilized diluant, we provide a practical algebraic formula that allows decision makers to evaluate the optimal starting point of the constant-volume Diafiltration step and to adapt it when considered prices change. Finally, we demonstrate the applicability and achievable benefit of the here presented approach on an industrial-scale case study using literature data.
F Veglio - One of the best experts on this subject based on the ideXlab platform.
-
whey protein concentrate production in a pilot scale two stage Diafiltration process
Separation Science and Technology, 2001Co-Authors: D Barba, Francesca Beolchini, D Cifoni, F VeglioAbstract:A pilot scale two-stage batch Diafiltration process for whey protein concentrate (WPC) production is presented in this work. This process has two main advantages: a significant water saving with respect to a single-stage Diafiltration process and a membrane surface saving with respect to a continuous multistage process. Every unit operation of the process has been experimented in a pilot scale (ultrafiltration, Diafiltration, drying), in order to produce a WPC powder. Lactose content decreased from about 75% (of whey) to 4.5% (calculated as mass of lactose per total solute mass) and proteins increased from 15% to 83% (calculated as mass of proteins per total solute mass), with a water consumption of about 1.5 L/L of whey. Permeability tests enabled the calculation of the main mass-transfer resistances through the membrane: the intrinsic membrane resistance, RM , was 13.8 ± 0.1, the one due to fouling, RF , was 3.68 ± 0.04, and the one due to polarization, RG , was estimated at 2.4 ± 0.4 (at 150 kPa TMP) 1...
-
minimizing water use in Diafiltration of whey protein concentrates
Separation Science and Technology, 2000Co-Authors: D Barba, Francesca Beolchini, F VeglioAbstract:A multistage countercurrent Diafiltration process for whey protein concentrates (WPC) production is presented. Experimental tests of whey Diafiltration have validated a mathematical model for the concentration of components in the permeate for the case of washing with a dilute solution containing whey components. This model has been used together with material balances in order to simulate the multistage process. Water saving with respect to a single-stage conventional Diafiltration was demonstrated. In the case of a WPC production of 95.5% from the whey of a local dairy farm which contained 7.7 g/L proteins, 43 g/L lactose, 1.1 g/L nonproteic nitrogen, and 5.4 g/L ashes, the necessary volumes of water, V D (volume of water per volume of treated solution), needed decreased from 5.4 for a single stage to 2.9 for a two-stage process down to 1.5 for a six-stage process. The adopted procedure can be easily applied to any Diafiltration process.
-
water saving in a two stage Diafiltration for the production of whey protein concentrates
Desalination, 1998Co-Authors: D Barba, Francesca Beolchini, F VeglioAbstract:Abstract Whey proteins are of higher nutritive value than many other animal proteins. This makes whey an attractive raw material in the production of whey protein concentrates (WPC) [1]. These ingredients have been used extensively in various segments of the food industry including dairy, bakery, meat industry, confectionery, beverage production and the manufacture of baby and dietary foods. Due to the progress in membrane technology, it is possible now to obtain WPC containing the desired quantities of soluble native proteins, lactose and mineral matter [1]. To obtain WPC with 65% of proteins or more in the solid content, water is normally added during ultrafiltration, realising a Diafiltration operation. The WPC thus obtained contain lower concentration of lactose which broadens their use in food products applications [1]. The Diafiltration operation is characterized by high water consumption [2]. The aim of this work is the study of a two stage Diafiltration process, where water consumption results to be lower with respect to conventional Diafiltration.