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Concept of industrial-scale diafiltration systems

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Abstract

The use of diafiltration is now the state-of-the-art in the food and beverage, biotech and pharmaceutical industry. In this paper, the advantages and disadvantages of the most common process modes of diafiltration, batch and continuous, are discussed. Further, the new concept of counter-current diafiltration, which leads to a significant reduction of diafiltration liquid consumption, is introduced. The three concepts are compared in a case study of a plant to concentrate a protein solution. In this study, the process layouts are based on a DSS GR 61 membrane (MWCO of 20,000 Dalton and 100% protein rejection) and a DSS plate-and-frame module. Each continuous diafiltration processes consist of 3 pre-filtration steps followed by 2 to 10 diafiltration steps. The different process layouts are optimized and compared considering technical and economical aspects. It is revealed that all three concepts show similar separation performance. However, taking a 4-stage diafiltration process, the continuous diafiltration requires 40% smaller membrane area compared to counter-current diafiltration, but 140% more diafiltration liquid. Further, comparing batch and counter-current diafiltration, the membrane area for counter-current diafiltration is 115% larger, while the diafiltration liquid requirement of batch process is 74% higher. The trends are also reflected in the higher investment cost and membrane area related operating costs of the counter-current diafiltration process but might be balanced by reduced costs for pre-treatment of the diafiltration liquid and concentration/post-treatment of the permeate. Furthermore, the study demonstrates that addition of fresh diafiltration liquid increases the diafiltration liquid consumption but directly reduces investment and membrane area related operating costs. It can be therefore concluded that counter-current diafiltration is a novel approach to develop case-specific optimized diafiltration processes.

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... This plate-and-frame module was chosen as a case study, because it exhibits 3D velocity fields and significant entrance/outlet effects and, furthermore, is a versatile membrane module widely used in research, e.g. [7,[13][14][15][16][17][18][19]. Both the Grober [5,13] and the Rautenbach [7] correlations have been applied to predict the mass-transfer coefficient in this module. ...
... (9). The following mass-transfer correlation was obtained by fitting Eq. (11) to the Sh numbers predicted by CFD: Sh = 0.142Re 0.46 Sc 0.37 (15) This correlation has average and maximum relative errors of 1 and 4%, respectively, in the range of 64 < Re < 570 and 450 < Sc < 8900. The Reynolds number exponent in the mass-transfer correlations for feed channel geometries with 2D distribution of velocity and concentration, at laminar flow regime, is either 0.33 or 0.5 depending whether the velocity profiles are fully developed or developing, e.g. ...
... The values of Sh obtained by CFD, the correlations obtained by the curve fitting of the CFD results (Eqs. (15) and (16)) and the VVM results (Eq. (18)) as well as the Levêque, Grober and Rautenbach correlations are compared in Fig. 11. ...
Article
The flow structure and solute concentration distribution in a nanofiltration/reverse osmosis plate-and-frame module with radial thin feed channels that have considerable entrance and outlet effects was determined by computational fluid dynamics (CFD). Simulations were performed for binary aqueous solutions, Reynolds (Re) numbers in the range of 64–570 (based on the channel height) and Schmidt (Sc) numbers between 450 and 8900.The CFD simulations showed that both the velocity field and the solute concentration distribution exhibit important 3D effects and, at rather low Reynolds numbers (Re≥118), flow instabilities start to appear in the entrance/outlet regions. However, those instabilities do not affect significantly the average concentration polarization on the membranes surface up to the maximum Reynolds number simulated (Re=570). The friction factors predicted by CFD were in agreement with the corresponding experimental values for the range of Re numbers investigated.The simulations allowed the determination of a mass-transfer correlation at vanishing mass-transfer rates and a correlation for mass-transfer correction factor. The obtained mass-transfer correlation at vanishing mass-transfer rates was compared with the ones available in the literature as well as with the Sherwood numbers determined by the velocity variation method, using diluted aqueous solutions of glycerol. It was also found that a generalized mass-transfer correction factor correlation for high mass-transfer rates, previously developed for membrane modules with 2D configurations, is still valid to predict the average concentration polarization in the module investigated.
... However, the 0.1 µm membranes used in the dairy industry for milk protein fractionation also retain most bacteria, which thus accumulate in the retentate. Notably, it is common in the industry to partially recirculate the retentate during MF or ultrafiltration, where, for example, higher counts of microorganisms accumulate in the feed flow with time during the crossflow MF before a diafiltration step [10,11]. These effects support biofouling on the membrane surfaces, which increases the fouling resistance and may become critical in terms of hygiene due to the fact that microbial growth can occur in deposited protein layers similar to biofilms produced by the microbiome itself. ...
... Membranes 2020,10, 326 ...
Article
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This study determined the maximum possible filtration time per filtration cycle and the cumulated number of operational hours per year as a function of the processing temperature during milk protein fractionation by 0.1 µm microfiltration (MF) of pasteurized skim milk. The main stopping criteria were the microbial count (max. 105 cfu/mL) and the slope of the pH change as a function of filtration time. A membrane system in a feed and bleed configuration with partial recirculation of the retentate was installed, resembling an industrial plants’ operational mode. Filtration temperatures of 10, 14, 16, 20, and 55 °C were investigated to determine the flux, pH, and bacterial count. While the processing time was limited to 420 min at a 55 °C filtration temperature, it could exceed 1440 min at 10 °C. These data can help to minimize the use of cleaning agents or mixing phase losses by reducing the frequency of cleaning cycles, thus maximizing the active production time and reducing the environmental impact.
... Following studies extended this result for more complex process models and diluant utilization schemes by maximization of mass flow through the membrane [26] or by means of optimal control theory [27,28]. However, as pointed out by [29] and other related studies, there is a need to account for the consumption of diluant if its price is significant. Jaffrin and Charrier [6] proposed variable volume diafiltration approach for reduction of water consumption for UF/DF of water-ethanol solutions of bovine serum. ...
... and (29). Resulting expression J (w T , w D , c * ) can be differentiated w.r.t. ...
Article
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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.
... Clarification and concentration of Spirulina extracts by the means of micro-and ultrafiltration (Jaouen et al. 1999) and nanofiltration and reverse osmosis (Chaiklahan et al. 2011) has been reported in literature. Diafiltration of sugars with ultrafiltration membranes is a very well explored field (Lipnizcki et al. 2002). During this pretreatment step preservation of proteins is important, since denaturation could release the chromophore allowing it to permeate through the ultrafiltration membrane. ...
Article
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A dia-ultrafiltration process for purification of phycocyanin-based solutions is presented. The aim of the process is to remove additives present in a commercial food colorant, mainly D-trehalose. Optimization of parameters such as molecular weight cut-off, initial concentration of feed, process temperature and transmembrane pressure has been conducted. The focus has been on obtaining a fast and effective removal of additives, while at the same time keeping operational conditions mild enough to avoid degradation and hereby loss of colour.
... As suggested by Fikar, Kovacs, and Czermak (2010), DF is a membrane-assisted process that is designed to achieve the twinobjectives of concentrating and purifying a multi-solute system according to a specific wash-water utilization strategy. DF is considered a work of art in membrane separation technology, where the water is added into the batch tank until the desired concentration of the retentate is reached (Lipnizki, Boelsmand, & Madsen, 2002). ...
... The study revealed also the impact on the economics of a process is different from the environmental impact. For example, while increasing the facility capacity increases water and energy consumption, it can have a positive impact on the cost of [LMH] 200 Duration [Hrs] Item Energy required Source/Comment PW and CIP production 558 kJ/L [28] SIP Production 797 J/s-L Energy to heat water from 25°C to 250°C Filtration 50 J/s-m 2 [47] Media and Buffer Preparation 69.0 J/s-L [48] Liquid waste treatment [Heat to 80 Celsius] 639 J/s-kg-water Inactivation of mammalian cells at 85°C [34] Lighting 15 J/s-m 2 [33] ...
Article
Life-cycle assessment (LCA) is an environmental assessment tool that quantifies the environmental impact associated with a product or a process (e.g. water consumption, energy requirements, and solid waste generation). While LCA is a standard approach in many commercial industries, its application has not been exploited widely in the bioprocessing sector. To contribute towards the design of more cost-efficient, robust and environmentally-friendly manufacturing process for monoclonal antibodies (mAbs), a framework consisting of an LCA and economic analysis combined with a sensitivity analysis of manufacturing process parameters and a production scale-up study is presented. The efficiency of the framework is demonstrated using a comparative study of the two most commonly-used upstream configurations for mAb manufacture, namely fed-batch (FB) and perfusion-based processes. Results obtained by the framework are presented using a range of visualization tools, and indicate that a standard perfusion process (with a pooling duration of 4 days) has similar cost of goods than a FB process but a larger environmental footprint because it consumed 35% more water, demanded 17% more energy, and emitted 17% more CO2 than the fed-batch process. Water consumption was the most important impact category, especially when scaling-up the processes, as energy was required to produce process water and water-for-injection, while CO2 was emitted from energy generation. The sensitivity analysis revealed that the perfusion process can be made more environmentally-friendly than the FB process if the pooling duration is extended to 8 days. This article is protected by copyright. All rights reserved.
... DF is the industrial-scale unit operation for buffer exchange [3] and can also be run continuously, but requires a more complex setup than continuous filtration, as multiple filter units and intermittent dilution steps need to be included [52,53,21]. Rucker-Pezzini et al. [54] reported a single-pass DF process using three consecutive commercial SPTFF modules with interim retentate vessels into which the DF buffer was added. ...
Article
The biopharmaceutical industry has an ongoing interest in improving manufacturing efficiency and productivity while at the same time reducing manufacturing costs by developing intensified, linked and continuous processes. In recent years, upstream productivity of bioprocesses has improved significantly resulting in increased volumes and increased titers, which have put downstream processes under enormous pressure. Single Pass Tangential Flow Filtration (SPTFF) is a technology that offers an opportunity to reduce process volumes efficiently through inline concentration in one single pass through a series of membranes without the need for retentate recirculation. This technology links upstream and downstream operations and has the capability to ensure continuous production. This review seeks to investigate both early papers on SPTFF and recent developments in the field, including single-use SPTFF and 3D printed membrane modules. To our knowledge, this review is the first to address SPTFF and is aimed at gathering all relevant information about the topic, with a special focus on application in bioprocessing from which this technology has evolved. Due to a growing need for intensified processes, interest in SPTFF within the biopharmaceutical industry is increasing, hence the importance of gathering all relevant information on the topic in this review. The review starts with a thorough comparison between normal tangential flow filtration (TFF) and SPTFF, including principles, configuration, and typical features of these technologies. Also addressed are the design equations and how to tackle fouling. The review ends by providing relevant information about the main applications of SPTFF in bioprocessing as well as future perspectives on the operation. The review mainly deals with application in the biopharmaceutical industry but includes examples from the food industry and wastewater treatment.
... The selection of optimal diafiltration strategy in continuous processing is very case specific. In general, a reduced consumption of fresh diluant but a larger membrane area is required for the countercurrent approach (i.e., reintroduction of permeate as diluant in the process train) as compared to cocurrent process if the same degree of purification is to be attained (Lipnizki et al. 2002). etc. ...
... The selection of optimal diafiltration strategy in continuous processing is very case specific. In general, a reduced consumption of fresh diluant but a larger membrane area is required for the countercurrent approach (i.e., reintroduction of permeate as diluant in the process train) as compared to cocurrent process if the same degree of purification is to be attained (Lipnizki et al. 2002). ...
... Removal of excess salt can be obtained by dilution of the concentrate. Such activity called diafiltration is commonly used at the level of the ultrafiltration for desalting colloidal solutions [8][9][10][11][12][13][14]. ...
Conference Paper
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The work presents a proposal for desalination of chromium(III) wastewater by nafiltration combined with diafiltration. For the variant with a double diafiltration mode was obtained the double lowering salt retention in relation to classic nafiltration. On the basis of the results of the study, it was found that to obtain a high level of washing out salt dependent on the degree of concentration in the initial step of the process and the number of diafiltration steps. It was observed that the addition of a solvent (deionised water at pH 6.8) has led to an increase in pH in the solution, which in the case of a high level of chromium retention led to the formation of chromium(III) salt sediment and blocking the membrane. Therefore, in order to obtain the highest degree desalination of chromium(III) wastewater proposed to use a solvent pH of the tested solution and at least 2-3 times washing solution.
... Diafiltration is a method for removing permeable molecules (impurities, salts, solvents, etc.) from a solution to maximise the purity of desired substances such as proteins, polysaccharides, etc. (Frank et al., 2002;Li et al., 2009;Roma´n et al., 2009). Theoretical studies of the diafiltration process have been widely performed in recent years. ...
Article
This work presents a theoretical study of the diafiltration and concentration processes on xylo‐oligosaccharides (XOs) syrup using nanofiltration (NF). In our previous study of the separation performance of the NF process on XOs syrup, the models of flux (J v) and observed retention (R obs) of an NF membrane have been established. In the present study, these models were employed to construct the balance equations of syrup volume and XOs concentration in a feed tank. In experiments, the constant‐volume continuous diafiltration (CVCD) and the discontinuous diafiltration processes were implemented. In CVCD simulation, the flux curve predicted by the model agreed well with the experimental data. In discontinuous diafiltration simulation, the calculated total content of XOs was 94.5%, which was about 1.5% less than the experimental result (96.11%) given by discontinuous diafiltration operation on a XOs syrup with initial XOs content 83.5%.
... The following mathematical model (Eq. (1)) describes our type of diafiltration mode [19,22,23]. This model is based on a few assumptions: rejection factor of high molecular substances is equal to 100%, volume of the solution in the storage stirred tank remains steady and rejection factor of low molecular substance is constant. ...
Article
The methods of beer dealcoholisation can be divided in two large groups: physical and biological methods. One of the physical methods - reverse osmosis was chosen and studied. Four standard solutions were suggested for further research. These standard solutions contained basic substances of beer: water, ethanol and glucose. The effect of the substances added to the solution, and influence of retentate flow on the permeate flux were studied. The results of initial experiments were taken as the basis for further diafiltration process, where significant reduction of the ethanol concentration in the retentate was expected. Experimental results were compared with values calculated from mathematical model found in the cited literature. It was found out that the experimental data agree very well with calculated model data. During long-time process of diafiltration the concentration of ethanol decreased from the initial value 4.49 to 0.24 vol%. The studied diafiltration process is suitable for the dealcoholisation of investigated mixtures.
... Lin and Livingston (2007) demonstrated the use of a countercurrent nanofiltration membrane cascade for organic solvent exchange, although the extent of buffer exchange was only about 4-fold (corresponding to 77% exchange). Lipnizki, Boelsmand, & Madsen, (2002) presented limited results for a continuous countercurrent process for protein diafiltration based on earlier work by Madsen (2001) that showed the potential for reduced buffer consumption due to the countercurrent staging, although no quantitative analysis of the system performance was presented. Lutz (2015) described the use of a single-pass diafiltration process with diafiltration buffer added between stages (equivalent to repeated steps of concentration and dilution). ...
Article
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
... Counter-current DF, which suggests the recycling of UF, nanofiltration, or reverse osmosis permeates, represents an alternative to classical DF. However, it would require larger membrane areas in dairy plants ( Barba et al., 2000;Lipnizki and Madsen, 2002). Similarly, Foley (2006) studied the possibility of combining UF with variable-volume DF, which consists of adding water at a lower rate than the permeation flux, concentrating the solution simultaneously with purification by DF. ...
Article
High-milk protein concentrates (>80% on a dry weight basis) are typically produced by ultrafiltration (UF) with constant-volume diafiltration (DF). To maximize protein retention at a commercial scale, polymeric spiral-wound UF membranes with a molecular weight cut-off (MWCO) of 10 kDa are commonly used. Flux decline and membrane fouling during UF have been studied extensively and the selection of an optimal UF-DF sequence is expected to have a considerable effect on both the process efficiency and the volumes of by-products generated. The objective of this study was to characterize the performance of the UF-DF process by evaluating permeate flux decline, fouling resistance, energy and water consumption, and retentate composition as a function of MWCO (10 and 50 kDa) and UF-DF sequence [3.5×-2 diavolumes (DV) and 5×-0.8DV]. The UF-DF experiments were performed on pasteurized skim milk using a pilot-scale filtration system operated at 50°C under a constant transmembrane pressure of 465 kPa. The results showed that MWCO had no effect on permeate flux for the same UF-DF sequence. Irreversible resistance was also similar for both sequences, whatever the MWCO, suggesting that soluble protein deposition within the pores is similar for all conditions. Despite lower permeate fluxes and greater reversible resistance for the 5×-0.8DV sequence, the overall energy consumption of the 2 UF-DF sequences was similar. However, the 3.5×-2DV sequence required more water for DF and generated larger volumes of permeate to be processed, which will require more membrane area and lead to greater environmental impact. A comparative life cycle assessment should however be performed to confirm which sequence has the lowest environmental impact.
... In [10], time-optimal control of UF/DF described by famous limiting flux model was investigated and simple formula for optimal concentration to switch from concentration to the constant volume diafiltration mode (CVD) was derived. This result became an industrial practice to operate UF/DF processes despite that it does not account for minimization of the amount of utilized solvent which can represent a significant operational cost factor [11]. ...
Conference Paper
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Presented work deals with the cost optimal operation of batch ultrafiltration/diafiltration (UF/DF) processes. The economic optimization problem comprises two classical optimization criteria, namely minimum time and minimum diluant (solvent) consumption. In order to reflect the varying prices of individual parts of operational cost to the economically optimal process on longer time horizon, we treat the resulting optimization problem as a multi-objective one. We use analytical solution to this problem, obtained by applying Pontryagin's minimum principle, which provides conditions for switching of optimal control structure and for evaluation of economically optimal diluant utilization strategy. The here developed methodology is applied to the examples of UF/DF processes taken from the literature and economical benefits of using such advanced control strategy are discussed.
... In the first case, a solid-liquid biphasic system is placed in the filtration module, and usually it is used for the purification of solid by removing of small-size species or highly soluble in the washing solvent. On the other hand, when separation operation is performed in homogeneous phase, a solution is introduced in the filtration module (Lipnizki et al., 2002). Homogeneous-phase diafiltration is the basic principle of most advanced separation techniques such as polymer enhanced ultrafiltration (PEUF) or liquid-phase polymer-based retention (LPR) (Palencia, 2015;Palencia et al., 2017;Rivas et al., 2017;Huang and Feng, 2019). ...
Article
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Cite as: Espinosa-Duque A., Mora M.A., Palencia M. Modeling of constant-volume continuous diafiltration by solute distribution space's perturbations through geometric series: Part I:Inert system (Washing method). J. Sci. Technol. Appl. 11 (2021) 13-23. Abstract. A new modeling of the washing method during constant-volume continuous diafiltration is described. This model is based on the analysis of small perturbations experimented by a dissolution in the inner of a diafiltration module. Thus, the analysis of small perturbations promoted during the diafiltration process permits to conclude an analytical model to describe the concentration changes in function of system parameters (e.g., filtration factor, permeate volume, time). Mathematical expression for the description of retention profile is characterized to be a geometric series with constant ratio given by r = 1/(1+ϕ) with a corresponding equivalent exponential equation, in addition, all parameters of model are completely defined in term of physical variables. It is concluded that retention profiles of inert system are completely defined by two volumetric parameters related with the experiment design: "collecting tube volume" and volume contained in the filtration cell. However, if the minimal permeate volume produced by the perturbation is considered, then "collecting tube volume" is equal to membrane's permeability.
... The manufacture of MPC may thus require substantial use of water if a DF is performed (Gavazzi-April et al., 2018;Novak, 1992). It also generates significant volumes of milk UF and DF permeates, even under optimized conditions (Foley, 2006;Gavazzi-April et al., 2018;Lipnizki et al., 2002). For example, manufacturing around 60 � 10 3 kg of dried MPC80 or MPC85 from 1500 � 10 3 kg of milk would require between 243 and 871 kg of potable water during DF, and would generate between 1476 � 10 3 to 1973 � 10 3 kg of combined UF and DF permeates (Gavazzi-April et al., 2018). ...
Article
Milk protein concentrates (MPC) are increasingly used as protein fortifiers in food formulations, as a means to increase cheese yield, and in the manufacture of Greek-style yogurt. However, manufacturing of MPC requires significant volumes of input water and generates polluting by-products such as permeates and/or diafiltrates. Reverse osmosis was suggested to reduce the impact of both issues by reclaiming water from dairy fluids, thereby reducing the volumes of by-products to be treated. Filtration performance data was obtained from the reverse osmosis of dairy fluids, namely skim milk and ultrafiltration permeate, and from the polishing process of their respective permeates. It allowed the comparison of various water reclamation scenarios through a predictive analysis, which revealed that, without increasing operational costs, preconcentrating the skim milk prior the MPC manufacture would reduce the use of water and electricity by 35% and 10%, respectively, compared to a traditional process that consists in the concentration of skim milk by ultrafiltration, followed by the concentration of the resulting retentate by reverse osmosis.
... (2) a diafiltration step to purify the retentate by the addition of the diafiltration liquid and (3) a final concentration step to maximise the concentration of the high molecular weight solutes in the retained product [84]. ...
Article
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Short-chain fructooligosaccharides (ScFOS) are a group of linear fructose oligomers that include 1-kestose, 1-nystose and 1-β-fructofuranosylnystose. ScFOS, which naturally occur at low levels in different plant products, are of high interest as food ingredients because of their prebiotic character, organoleptic characteristics and technological properties. Two different industrial processes are used to achieve large-scale ScFOS production: inulin hydrolysis (enzymatic or chemical hydrolysis) or sucrose biotransformation by transfructosylation (enzymatic synthesis) using specific enzymes like fructosyltransferases and fructofuranosidases. Enzymatic ScFOS synthesis seems to be more advantageous than inulin hydrolysis since it is less expensive, and leads to lower molecular weight FOS. The biotechnological process described to carry out this catalysis includes the production of transfructosylation enzymes, separation, enzyme immobilisation and finally the ScFOS production and purification. Such ScFOS production processes may be conducted under submerged or solid-state fermentation under discontinuous or continuous conditions. Several methodologies with different economic/environmental costs and production yields have been described to carry out these ScFOS production stages, although industrial scale-up needs to be optimised. This review tries to address a revision about enzymatic ScFOS production methods and its scale-up to industrial levels.
... Compared to conventional tangential flow filtration (TFF) in which the retentate is pumped in a loop and passes the membrane module several times, single pass tangential flow filtration (SPTFF) is more suitable for integration into continuous manufacturing schemes. As early as 2002, Lipnizki [14]and co-workers conducted a theoretical study of batch and continuous diafiltration of a protein solution using between two and ten plate-and-frame membrane modules. They compared three operation modes: (i) batch diafiltration with retentate recycling and all modules operation in parallel, (ii) continuous diafiltration with the retentate passing the modules sequentially and the admixture of diafiltration buffer between the stages, and (iii) continuous counter-current diafiltration injecting fresh diafiltration buffer only once in the final stage and always using the permeate as diafiltration solution of the proceeding stage. ...
Article
Looking at current trends within downstream processing (DSP) of high value bioproducts, it shows that there are ongoing efforts in replacing batch processes by continuous variants. However, a unit procedure which still lacks a simple and compact continuous variant is diafiltration. Here, we present such a single piece of diafiltration equipment achieving continuous buffer exchange of up to 99.90%. The device is composed of a 3D-printed single pass diafiltration (SPDF) module containing two commercial ultrafiltration membranes. While the retentate is flowing through a narrow channel between the two membranes, the channels above and below can supply diafiltration buffer or remove permeate solution. The obtained results illustrate systematically the vulnerability of the device to the effect of concentration polarization at the membrane surface, and that this problem can be strongly reduced using an alternating direction of diafiltration buffer perfusion through the membranes as process inherent backflush. By this, a quasi-stationary operation could be obtained during continuous diafiltration, making the device an interesting option for in-process buffer exchange.
... Although most saccharides are neutral molecules in aqueous solution, the presence of electrolyte can change the electric layer on the membrane surface, membrane pore size distribution and solute properties, which leads to increase of saccharide transfer due to solute dehydration induced by the electrolyte [91]. Diafiltration process is an effective technique to achieve both high purification rate and economically acceptable permeate flux, and thus it has been widely in food, beverage, and biotechnological industries to concentrate protein or to recover saccharides [92]. Especially, Wang et al. has proven that the diafiltration process by using NF membrane is a feasible process to concentrate OS and simultaneously remove NaCl from soybean whey wastewater [93]. ...
Article
Saccharide production is critical to the development of biotechnology in the field of food and biofuel. The extraction of saccharide from biomass-based hydro-lysate mixtures has become a trend due to low cost and abundant biomass reserves. Compared to conventional methods of fractionation and recovery of saccharides, nanofiltration (NF) has received considerable attention in recent decades because of its high selectivity and low energy consumption and environmental impact. In this review the advantages and challenges of NF based technology in the separation of saccharides are critically evaluated. Hybrid membrane processes, i.e., combining NF with ultrafiltration, can complement each other to provide an efficient approach for removal of unwanted solutes to obtain higher purity saccharides. However, use of NF membrane separation technology is limited due to irreversible membrane fouling that results in high capital and operating costs. Future development of NF membrane technology should therefore focus on improving material stability, antifouling ability and saccharide targeting selectivity, as well as on engineering aspects such as process optimisation and membrane module design.
... water usage of 62 kg water/ kg whey protein was estimated to produce WPI. The water consumption of both processes was evaluated to be around the same order of magnitude, as a proper diafiltration design will reduce the water usage of the pea fractionation process, which was demonstrated by (Gavazzi-April, Benoit, Doyen, Britten, & Pouliot, 2018;Lipnizki, Boelsmand, & Madsen, 2002). Moreover, so far the presented values are based on lab scale experiments. ...
Article
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To meet the consumer demand for minimally processed foods and clean labels, the potential of processes where chemicals are omitted and only water is used needs to be explored. Mild wet fractionation of yellow pea, a water-only process, is investigated on maximum separation and efficient water use. By only using water, starch and protein from pea could be successfully separated, resulting in fractions high in yield and purity. Multiple washing steps of both the starch and the non-soluble protein fraction were performed to enhance separation. As a result of starch- and non-soluble protein pellet washing, the starch fraction was further depleted in protein and the protein solubility in the non-soluble protein fraction decreased. Ultrafiltration of the soluble protein fraction served to concentrate and the extracted water has potential to be reused in the process. Small solutes were concurrently extracted, which resulted in a higher protein purity in the soluble protein concentrate of 75%. The presented method has potential for upscale use in industry to produce protein fractions comparable to protein isolates obtained through conventional fractionation.
Chapter
The ultrafiltration (UF) with diafiltration is the state-of-the-art process in the bulk pharmaceutical industry to separate solutions containing high and low molecular weight solutes. By applying UF with diafiltration, a feed stream can be separated into a concentrate with a high concentration of high molecular weight solutes and a permeate, which is nearly 100% free of high molecular weight solutes. The UF with diafiltration process commonly consists of three stages that include a preconcentration stage achieving similar concentrations of low molecular weight components in retentate and permeate, a diafiltration stage to purify retentate by addition of a diafiltration liquid, and a final concentration stage to maximize the concentration of high molecular weight solutes in retentate. UF combined with diafiltration is used after the fermentation to separate the citric acid from the biomass. The UF permeate can then be further purified by using reverse osmosis (RO)/nanofiltration (NF) to remove any remaining impurities such as biomass, salts, and sucrose and thus minimizing the posttreatment. The purified citric acid is then mixed with calcium carbonate resulting in calcium citrate containing approximately 75% of citric acid. Electrodialysis (ED) is used as a recovery method for the citric acid to replace the lime/sulfuric acid precipitation and thus avoid the production of calcium sulfate as a by-product from the citric acid production.
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Membrane filtration represents a unique separation technique as it can be employed for both concentrating and purifying a multicomponent process stream. To achieve these twin-objectives, diafiltration is required. Diafiltration is an operation mode of a pressure-driven membrane filtration process in which a diluant (i.e.,∼water or any other solvent or buffer) is added to the process liquor in order to enhance the degree of separation of membrane-retained macrosolutes from membrane-permeable microsolutes. Depending on the separation target, diafiltration may be performed with microfiltration, ultrafiltration, nanofiltration, or reverse osmosis membranes. The separation target can be reached by using either batch or continuous processing mode. Diafiltration is an indispensable tool in separating multicomponent process streams and widely used in the food and beverage, chemical, biotechnological, and pharmaceutical industries. This article introduces the reader to the fundamentals of diafiltration. It provides a brief survey on the most important applications and discusses the various configurations, general design equations, control strategies, and diluant utilization strategies used in batch and continuous diafiltration practiceKeywords:diafiltration;microfiltration;ultrafiltration;nanofiltration;reverse osmosis;batch membrane filtration;continuous processing
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Cambridge Core - Chemical Engineering - Membrane Filtration - by Greg Foley
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A brief outline on the membrane-based integrated systems precedes the essential part of this chapter. The classification of different hybrid processes is proposed along with the four main groups, that is, membranes with conventional unit processes, membrane contactors, membrane with aggregation processes, and membrane reactors.Essentially, this chapter comprises an overview of major applications of membrane-based integrated systems in various industry sectors, such as textile, tannery, pulp and paper, metal finishing, and electronic and food industry.Attention is focused not only on those membrane processes that have become well entrenched in industrial practice in recent years, delivering a long reference list of successful implementations and know-how, but also on some membrane-based integrated processes that are in use only in very specific applications and also at the laboratory level, which are waiting for a broader successful industrial implementation, anticipating a sharp development and generally many breakthroughs in future.
Article
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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.
Article
Process streams in biorefineries are complex mixtures of various kinds of substances that have to be separated and concentrated. The main components in biorefinery process streams are cellulose, hemicelluloses, lignin and extractives. Due to the complex nature of these streams, fractionation often has to be performed in a number of successive stages, using a cascade configuration. Suspended solids and colloidal matter are separated by microfiltration (MF). Macromolecules, for example hemicelluloses and protein, are concentrated by ultrafiltration (UF). Monosaccharides, multivalent inorganic ions and low-molar-mass lignin are concentrated by nanofiltration (NF) and salts are removed by reverse osmosis (RO). Retained solutes can be purified by diafiltration (DF). The basic principles, process design and optimization of MF, UF and DF are reviewed in this chapter. The requirements for membrane plants in pulp and paper mills are very similar to the industrial challenges in lignocellulosic biorefineries.
Article
The current study carried out, developed a protocol to efficiently process laccase from fermentation broths of Ganoderma sp. WR-1. Selection of a downstream protocol based on required yield and purity was achieved. Purification using fractional ammonium sulphate precipitation, three phase partitioning, ultrafiltration, diafiltration, and chromatography techniques were investigated. Ammonium sulphate and three phase partitioning resulted in a loss of 20% and 40% laccase activity. Successful ultrafiltration required separation of the extracellular polymeric substances (EPS) which was formed during fermentation. Freeze-thawing of the broth post-fermentation, followed by depth and microfiltration separated the EPS successfully. Operating parameters of pH, temperature and transmembrane pressure during ultrafiltration were optimized as 7, 21°C and 25psi respectively. Yields of 97% and ease of scalability made ultrafiltration the operation of choice for laccase concentration. Further product improvement by diafiltration in different operational modes, mode 1 (pre-diafiltration followed by post-concentration) and mode 2 (pre-concentration followed by post-diafiltration) using 10 and 30kDa membranes was carried out. Diafiltration, using a 30kDa membrane in mode 1 resulted in 3.7-fold purification with 90% yields. Anion, cation and hydrophobic interaction chromatography of the diafiltered broth to increase fold purity was performed. Anion exchange chromatography was the most suited technique as a substantially purified laccase was obtained with overall yields of 81%.
Article
Galactosyl-oligosaccharide (GOS) is a prebiotic carbohydrate, produced from lactose hydrolysis, that serves as a value-added functional food element for humans. Now GOS can be produced through enzymatic reaction with lactose either in batch mode or with immobilized enzyme on membrane. In the second case, the main concern is the fouling of the membrane that could reduce both the GOS yield and purity. The present study is thus an attempt to project the superiority of a membrane reactor called the rotating disk membrane bioreactor (RDMBR) over batch mode to obtain purified GOS with high yield. It was found that GOS yield and purity were 32.4% and 77% respectively in batch mode followed by diafiltration-assisted nanofiltration. However, in the immobilized state they were 67.4% and 80.2% at 105 rad s–1 membrane speed. Retention of monosaccharides that inhibit enzyme in the reaction volume of batch mode reduced the yield of GOS. On the contrary, simultaneous production and purification of GOS in RDMBR led to a high yield of GOS.
Conference Paper
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An economically optimal operation of batch diafiltration processes is studied. The processes are characterized by complex membrane transport models that adequately describe non-ideal membrane characteristics of real-life systems. We consider the optimization criterion which comprises two conflicting objectives, a minimization of processing time and a minimization of solvent consumption. The problem is treated in the multi-objective form in order to investigate the impact of operational cost factors on optimal operation policy. Thanks to the application of Pontryagin's minimum principle (PMP), we find the economically optimal operation of studied process in the analytical form. Developed methodology is applied to two case studies taken from literature.
Article
This work aimed to separate proteins and polyphenols from rapeseed stem extracts. Results showed that coagulation with 40 % w/w ethanol and ultra-filtration with the 10 kDa membrane were two efficient methods for polyphenols purification. The purity of polyphenols increased from 80.3 % to 97.0 % after separation. The combination of ethanol coagulation with ultrafiltration permitted decreased the ethanol consumption from 40% w/w to 10 % w/w while maintaining high polyphenols purity. Significant protein loss at room temperature was observed during the stability test, which emphasizes the importance of elaborating a fast and effective separation method for rapeseed stem extracts.
Article
Diafiltration is a membrane filtration technique that rapidly removes permeable molecules from a solution by controlling the tangential and orthogonal flows over a membrane and by replenishing the permeate with an equivalent amount of replacement buffer. However, its application to the purification of many key biomaterials and nanomaterials has been limited by the large dead volume (>10 mL) that is required to automate the process. To address this challenge, we have developed a diafiltration-on-a-chip device that can process low-volume samples (50 µL). The key innovation of this device is a magnetically-driven on-chip peristaltic pump that is able to continuously drive fluid flow at rates as high as 50 mL/hr with minimal external instrumentation and a dead volume of <50 µL. To demonstrate the utility of this device, we purified microbeads from dye with >99% purity and >96% retention within two hours. We additionally showed that cells could be purified from microbeads with >97% purity and >97% retention in two hours. Because our approach requires minimal instrumentation, it is well suited for on-chip parallelization, which was demonstrated by incorporating four complete diafiltration systems onto a single credit card-sized chip.
Article
The direct utilisation of side streams from membrane processing and evaporation is of great potential interest for dairies to reduce water consumption. In an analytical screening of 89 industrially obtained processing side streams, samples varied in pH and conductivity in broad ranges of 4.22 to 7.56 and 0.001 to 0.949 Siemens per meter, respectively. Detailed compositional data of the side streams enabled an assessment of their applicability as diafiltration (DF) media for milk protein purification during microfiltration (MF) or ultrafiltration (UF). Microfiltration experiments with simulated nanofiltration (NF) permeates showed that slight compositional variations of DF media can significantly affect milk filtration performance. Analyis of dairy side streams regarding chemical milieu followed by assessment of their applicabilty as DF medium and testing of single effects on microfiltration.
Article
Milk protein fractionation for casein/whey protein separation by microfiltration in diafiltration mode was investigated using washing waters differing in pH, calcium content and ionic strength. Properties of the deposit layer and process efficiency were assessed as functions of diafiltration progress and deposited layer structures were analysed. Results were compared with findings obtained in crossflow mode with a gradual change from milk to diafiltration medium. Deionised water as well as softened water induced a significant increase of deposited casein layer hydration, thereby increasing flux levels and separation efficiency. Dependent on water hardness, tap water was found to induce fewer changes to the deposit hydration and process performance indicating less change of casein micelles. These findings are consistent with the generic colloidal behaviour of casein micelles as previously determined through laboratory experiments. Therefore, waters with a certain degree of hardness could be recommended as the most suitable diafiltration medium not requiring pre-treatment.
Article
Besides deionised water, tap or softened water could be used as diafiltration media for separation and purification of the casein fraction from milk by means of membrane technology. The effect of compositional differences on key properties of casein micelles was investigated with these media and simulated milk serum as reference at laboratory scale under conditions mimicking typical industrially applied diafiltration processes. Evaluation of zeta-potential, particle size distribution, voluminosity as well as casein and calcium composition revealed marked differences of micellar attributes at temperatures of 10 and 50 °C depending mainly on the medium hardness. While tap water induced a slight micellar contraction, dehardened water types differently fostered a swelling that was followed by partial disintegration over contact time especially at 50 °C. Results demonstrate that water composition impacts micellar properties in typical DF conditions, which can, in consequence, be crucial for processing efficiency and product functionality of obtained casein products.
Article
Lycopene is a carotenoid found in tomatoes and other red fruits and vegetables. It is known for its antioxidant properties, which is associated with the prevention of cancer. Raw tomatoes and tomato‐based products are important sources of dietary lycopene. This study aimed to evaluate the integration of diafiltration and reverse osmosis processes to concentrate tomato pulp and to obtain a lycopene‐rich extract with a high antioxidant capacity and a low molecular weight. Diafiltration was efficient in desalting the tomato pulp, maintaining the lycopene concentration of the tomato at the same level as the whole tomato pulp. The permeate flux of the diafiltrated tomato pulp was 29.5 L·h−1·m−2 and the concentration factor of lycopene was 2.4. Additionally, it was found that the antioxidant capacity increased at the same rate than the lycopene content. Lycopene is a carotenoid found in tomatoes with higher antioxidant capacity. The membrane separation processes are considered as an alternative to the thermal processes, providing the concentration of these bioactive compounds present in the tomato using soft process temperatures, besides preserving the sensory and aroma characteristics. The integration of the processes with microfiltration and diafiltration membranes allows the production of a final product from the tomato with high concentration of lycopene, promoting the assistance in the prevention of various diseases related to human health, and a reduced soluble solids content of reduced molecular weight.
Chapter
In this chapter we derive necessary conditions for optimality (NCO) that can identify candidates for a solution of an OCP. We introduce analytical methods of solving the OCPs. Next, we discuss how gradients to optimisation criterion w.r.t. optimisation variables can be gathered. These represent a key issue in solving the OCP numerically. We present a few most popular numerical methods used to solve the problem of optimal control. We also discuss closed-loop implementation, handling of disturbances and nonlinear state-feedback control.
Book
This study concentrates on a general optimization of a particular class of membrane separation processes: those involving batch diafiltration. Existing practices are explained and operational improvements based on optimal control theory are suggested. The first part of the book introduces the theory of membrane processes, optimal control and dynamic optimization. Separation problems are defined and mathematical models of batch membrane processes derived. The control theory focuses on problems of dynamic optimization from a chemical-engineering point of view. Analytical and numerical methods that can be exploited to treat problems of optimal control for membrane processes are described. The second part of the text builds on this theoretical basis to establish solutions for membrane models of increasing complexity. Each chapter starts with a derivation of optimal operation and continues with case studies exemplifying various aspects of the control problems under consideration. The authors work their way from the limiting flux model through increasingly generalized models to propose a simple numerical approach to the general case of optimal operation for batch diafiltration processes. Researchers interested in the modelling of batch processes or in the potential industrial applications of optimal control theory will find this monograph a valuable source of inspiration, instruction and ideas. © Springer International Publishing Switzerland 2016. All rights reserved.
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The status of pilot-scale production methods for cellulose nanorods or nanocrystals and the 2,2,6,6-tetramethyl-4-hydroxypiperidine-1-oxyl (TEMPO) grade of cellulose nanofibrils are discussed. Both products appear to be poised for scale-up when markets develop, but there are a number of issues that need to be addressed. This chapter outlines concepts for conversion to continuous processes and other issues and concerns that need to be resolved for investments in commercial-scale production facilities. For large-scale production of cellulose nanocrystals, topic items include site selection, materials of construction, diafiltration, and acid recovery. For production of TEMPO grade fibrils, concerns include site selection, materials of construction, reaction kinetics relative to plant design, shear sensitivity of the treated pulp, and TEMPO recovery. Drying concerns are a significant problem in that currently practiced methods are energy intensive and do not provide readily dispersible nanoscale particles.
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Optimal control of any process can be achieved either in open or closed loop. In this chapter we concentrate mainly on the first class. It is devoted to definition of open-loop optimal control (dynamic optimisation) problems. We introduce three basic parts of an optimal control problem (OCP): objective functional, constraint functions, and process model and their common mathematical forms. Objective functional, optimisation criterion, or performance index represents mathematical expression of phenomenon for which, minimum (or maximum) we want to attain. The constraint functions of various types determine a search space of decision (optimisation) variables whose time evolutions or values are searched for. Process model function ties inputs, states and outputs of the process together and determines a search domain for optimisation procedure in a similar way the constraint functions do.
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Membrane processes are used in the context of filtration of liquid or gas mixtures and their purification. We focus our attention on the separation of dissolved species from liquid solutions. Such processes find applications mainly in biotechnology, pharmaceutical, and food industry, where highly purified final products are required or where the products can be degraded (chemically or biologically altered) by purification (e.g. proteins) using any of the standard separation techniques (e.g. distillation, evaporation). Current membrane technologies exploit a great variety of membrane processes such as processes based on membrane reactors, diafiltration, pervaporation, membrane distillation, electrodialysis, and so on. Common feature of these processes is the employment of the membrane separation principle. This chapter is devoted to brief presentation of basic theory of membrane separation and some of well-established pressure-driven membrane processes. Majority of attention is dedicated to diafiltration (DF) processes.
Article
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The yeast Yarrowia lipolytica is one of the most intensively studied non- conventional yeast species. They exhibit a remarkable performance in the efficient secretion of various heterologous proteins. The potential of having an in-situ isolation of the proteins would be very much desired since fermentation and product recovery can be carried out simultaneously. Incorporation of membrane technology for such purposes would be beneficial as an initial bulk volume reduction and partial purification. Consideration must be given to membrane as well as the protein as separation may be affected by the MWCO and various interactions possible between solvent, solute and the membrane which would lead to deterioration in efficiency and fouling. Studies related to Y. lipolytica cultivation and in-situ isolation which have been carried out are compiled and configuration of in-situ protein recovery for the yeast is proposed. The prospect for continuous recovery extracellular protein is highlighted.
Article
The new plate and frame module M39 from DSS is introduced. The main advantage is a reduction of pressure difference over the module compared to previous modules. This enables adjustment of the permeate flux according to needs. Sterile and sanitary design is discussed and the DSS UF-spiral constructed for heat sterilisation is introduced. The advantages and disadvantages of batch and continuous ultrafiltration plants are discussed. A new diafiltration concept — counter current diafiltration — is introduced and discussed together with the possibility of using purified permeate as diafiltration water. Ultrafiltration is only one part of a total factory. An important factor in obtaining the best economic and environmental process is determining the optimum overall process layout. The new diafiltration concept offers advantages by reducing environmental problems and investment requirements.
Madsen design of sanitary and sterile UF-and diafiltration plants
R.F. Madsen design of sanitary and sterile UF-and diafiltration plants, Separ. Purif. Technol., 22-23 (2001) 79-87.