Virus filtration is used for validation of virus clearance in the manufacture of monoclonal antibodies. Requirements for this size exclusion process include 10,000-fold reduction of virus particles and at least 95 % recovery of the monoclonal antibody in the permeate. The size difference between the rejected parvovirus particles, 25 nm, and monoclonal antibody, 10-12 nm, is about two. Membranes are designed with pore sizes around the average size of the parvovirus. Given the polydispersity in membrane pore size and virus particles, filter performance is dependent on membrane properties, feed and operating conditions. Compromised performance usually occurs due to product related foulants such as irreversible and reversible aggregates. Three commercial asymmetric hollow fiber membranes were investigated. The location of minute virus of mice entrapment within the membrane was determined by laser scanning confocal microscopy in the presence and absence of a monoclonal antibody or bovine serum albumin that forms irreversible aggregates. Experiments were conducted under constant flux for 12 h and constant pressure for 12.5-40 h. Membrane throughput was 900 L m(-2) and effective parvovirus removal (LRVs above 4) was verified under all conditions tested. Lower permeate fluxes and longer filtration times led to virus capture deeper within the membrane. Moreover, product-membrane interaction at low fouling conditions led to the migration of virus particle deeper within the membrane. Product aggregates, similar in size to virus particles led to displacement of virus particles deeper within the membrane and broadening of the entrapment zone. These results provide unique insights into virus filter performance.

Robust virus reduction and high permeability are characteristic properties of virus filters, which are modeled as having an asymmetric multilayer membrane structure with a pore size distribution. In this study, an advanced heterogeneous multilayer model for the multicomponent solution containing viruses, protein monomers and aggregates, has been developed to reproduce the filtration behavior, virus reduction, and virus/protein retention distribution in the virus filter with asymmetric membrane structure. Calculations based on the multilayer membrane structure with consideration of the effect of aggregate size and concentration numerically reproduce the experimental results that virus LRV (log reduction value) decreases when a large number of protein aggregates close in size to that of virus are present in the solution and that high virus LRV can be achieved even when the permeability is significantly reduced by the filtration of high concentration protein solution. In addition, the model calculation reproduced the filtration behavior of both constant flux and constant pressure filtrations with the same physical parameters, suggesting the equivalence of both filtration control modes. The advanced multilayer model was well able to reproduce filtration behavior, virus LRV and virus/protein retention distribution in the membrane by the same physical parameters at 1 mg/mL IgG. However, at 10 mg/mL IgG, while filtration behavior and virus LRV could also be reproduced, the virus/protein retention distribution in the membrane could not be well reproduced. This may simply indicate the possibility that larger sized aggregates that do not follow the size exclusion mechanism may be present in the concentrated feed solution.

This study aims to develop fouling-resistant membranes utilizing zwitterionic polymers for an integrated electrocoagulation (EC) and nanofiltration (NF) process to effectively remove microcystin-LR (MC-LR). The fabricated membranes were thoroughly characterized through contact angle measurements, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The efficacy of these modified membranes was investigated for synthetic microcystin removal, employing both commercial NF 270 membranes and modified NF 270 with zwitterionic polymers. Furthermore, real lake water containing microcystin was subjected to crossflow filtration using both commercial and modified NF membranes. The results indicated that the zwitterionic polymer-modified membranes demonstrated significantly better fouling resistance, with flux decline reduced from 37% to 15.5%, and improved microcystin-LR removal from 95% to 99.5% compared to unmodified membranes. To further enhance performance and meet drinking water standards, an EC step was implemented as a pretreatment for microcystin removal. The integrated EC-NF system exhibited superior performance, achieving complete MC-LR removal (below detection limit) and a 27% improvement in flux compared to the individual processes of either EC or NF. This enhancement in performance suggests the potential of this innovative integrated membrane system for applications in water treatment processes, particularly in addressing challenges related to fouling and contaminant removal. The comprehensive analysis and promising outcomes presented in this study contribute valuable insights to the advancement of membrane technology for sustainable water purification.

Wound dressings used in medical applications serve as a protective barrier for wounds, creating an environment that promotes wound healing. The typical traditional wound dressings often present challenges, including weak barrier function and tendency to adhere to wounds. Therefore, there is a critical need to develop advanced wound dressing with strong antibacterial properties that can prevent the spread of infection and accelerate the healing process. To develop hydrogels with antibacterial properties, silver nanoparticles (AgNPs) derived from 1 mM AgNO 3 using a green catalyst matcha green tea extract ( camellia sinensis) were incorporated into chitosan and alginate This was accomplished by mixing silver nitrate and green tea extract to produce the nanoparticles, which were then added to the hydrogel using crosslinkers. The synthesized nanomaterials and hydrogels were characterized using UV-VIS spectroscopy, TEM, EDX, FTIR, and SEM techniques. Their antimicrobial efficiency has been evaluated through inhibition zone assays, antibiofilm evaluation against P.aeruginosa, E. coli, S. aureus, C.albicans, and A.niger, and minimum inhibitory concentration (MIC). It was found that, novel hydrogel, infused with AgNPs, exhibited superior water absorption and retention, ensuring a moist wound environment while effectively absorbing a substantial wound exudate. Additionally, the antimicrobial hydrogel demonstrated robust mechanical properties and potent antimicrobial activity. This study highlights the exceptional antibacterial properties of a newly developed natural polymer hydrogel incorporated with Ag nanoparticles with anti-inflammatory action. Hence, the silver-loaded hydrogel proves to be an ideal wound dressing material.

Over the past few decades, significant efforts have been dedicated to advancing technologies for the removal of micropollutants from water. Achieving complete pure water with a single treatment process is challenging and nearly impossible. One promising approach among various alternatives is adopting hybrid technology, which is considered as a win-win technology. It utilizes the advantages of each technique, resulting in the enhancement of wastewater treatment. This pioneering idea is designed to significantly enhance water quality, addressing real-world implementation hurdles, and offer a promising solution to the worldwide issue of water scarcity. This review assesses the merits and drawbacks of the hybrid photocatalytic membrane technology employed in wastewater treatment. Notably, this hybrid process not only improves the membrane filtration capacity and permeates water quality but also enhances the antifouling performance of the membrane. However, it is crucial to acknowledge potential drawbacks, such as membrane structure degradation and photocatalytic activity loss in nanoparticles during the operation period. While improvements in wastewater treatment efficiency are evident, there remains ample room for further enhancements. The review summarizes the future directions and challenges of implementing such an integrated system.

The growing demand for viral vectors as nanoscale therapeutic agents in gene therapy necessitates efficient and scalable purification methods. This study examined the role of nanoscale biomaterials in optimizing viral vector clarification through a model system mimicking real AAV2 crude harvest material. Using lysed HEK293 cells and silica nanoparticles (20 nm) as surrogates for AAV2 crude harvest, we evaluated primary (depth filters) and secondary (membrane-based) filtration processes under different process parameters and solution conditions. These filtration systems were then assessed for their ability to recover nanoscale viral vectors while reducing DNA (without the need for endonuclease treatment), protein, and turbidity. Primary clarification demonstrated that high flux rates (600 LMH) reduced the depth filter’s ability to leverage adsorptive and electrostatic interactions, resulting in a lower DNA removal. Conversely, lower flux rates (150 LMH) enabled >90% DNA reduction by maintaining these interactions. Solution conductivity significantly influenced performance, with high conductivity screening electrostatic interactions, and the model system closely matching real system outcomes under these conditions. Secondary clarification highlighted material-dependent trade-offs. The PES membranes achieved exceptional AAV2 recovery rates exceeding 90%, while RC membranes excelled in DNA reduction (>80%) due to their respective surface charge and hydrophilic properties. The integration of the primary clarification step dramatically improved PES membrane performance, increasing the final flux from ~60 LMH to ~600 LMH. Fouling analysis revealed that real AAV2 systems experienced more severe and complex fouling compared to the model system, transitioning from intermediate blocking to irreversible cake layer formation, which was exacerbated by nanoscale impurities (~10–600 nm). This work bridges nanomaterial science and biomanufacturing, advancing scalable viral vector purification for gene therapy.

Tangential flow microfiltration is easily adapted for batch and continuous bioreactor clarification. The permeate can be introduced directly to the subsequent capture step. However, the commercial use of tangential flow filtration (TFF) is limited by membrane fouling, leading to a compromised performance. Here, we explored the possibility of reducing membrane fouling by integrating a hydrocyclone as the primary clarification operation. The overflow from the hydrocyclone was introduced directly as the feed to the microfiltration module. Chinese hamster ovary cells were used as the feed stream to investigate the feasibility of this integrated process. A range of cell viabilities from 0% (cell lysate) to 96% were investigated. The cell densities ranged from 0.9 to 10 million cells per mL. Two commercially available hollow fiber microfiltration membranes were used, an essentially symmetric membrane and a reverse asymmetric membrane where the more open support structure faced the feed stream. The reverse asymmetric membrane was more resistant to fouling in the absence of an integrated hydrocyclone. Integrating a hydrocyclone led to a reduction in the flux decline for the symmetric membrane, but did not affect the performance of the reverse asymmetric membrane. The careful choice of membrane morphology and pore size is important when designing an integrated process.

Virus filtration is used to ensure the high level of virus clearance required in the manufacture of biopharmaceutical products such as monoclonal antibodies. Flux decline during virus filtration can occur due to the formation of reversible aggregates consisting of self-assembled monomeric monoclonal antibody molecules, particularly at high antibody concentrations. While size exclusion chromatography is generally unable to detect these reversible aggregates, dynamic light scattering may be used to determine their presence. Flux decline during virus filtration may be minimized by pretreating the feed using a membrane adsorber in order to disrupt the reversible aggregates that are present. The formation of reversible aggregates is highly dependent on the monoclonal antibody and the feed conditions. For the pH values investigated here, pretreatment of the feed using a hydrophobic interaction membrane adsorber was the most effective in minimizing flux decline during virus filtration. Ion exchange membranes may also be effective if the monoclonal antibody and membrane are oppositely charged. Consequently, the effectiveness of ion exchange membrane adsorbers is much more dependent on solution pH when compared to hydrophobic interaction membrane adsorbers. Size based prefiltration was found to be ineffective at disrupting these reversible aggregates. These results can help guide the development of more effective virus filtration processes for monoclonal antibody production.

Membrane technology offers the potential for low-footprint solutions for industrial separation processes. However, using hazardous and conventional toxic solvents in membrane fabrication has raised sustainability concerns, prompting researchers to seek safer, bio-based solvent alternatives. Further disposal of used membranes is problematic. Both these concerns adversely affect the overall life cycle analysis. Green chemistry principles aim to reduce hazardous substances in chemical applications. Many studies have explored replacing conventional toxic solvents with less harmful green solvents. This opinion article covers the most recent trends, challenges, future directions, and advancements in sustainable membrane manufacturing over the past 4 years. These advances will lead to more sustainable membrane processes.

Efficient bioreactor clarification for harvesting virus particles is often challenging. Tangential flow filtration is attractive as it can be easily adapted for batch and perfusion operations. Here the feasibility of using reverse asymmetric hollow fiber membranes, where the more open support structure faces the feed stream, has been investigated for harvesting adeno associated virus serotype 2. The open support structure of these membranes stabilizes a secondary membrane consisting of rejected particulate matter. It is essential that the stabilized secondary membrane remains highly permeable. Flux stepping experiments were conducted in total recycle mode in order to determine the critical flux. The critical flux is the maximum stable flux. Higher fluxes lead to a rapid increase in transmembrane pressure under constant flux operation. The critical flux is shown to increase with increasing wall shear rate (feed flow rate). The reduction in turbidity of the permeate relative to the feed decreases with increasing wall shear rate. Harvesting adeno associated virus was conducted at a wall shear rate of 2000 s-1. The permeate flux was set at 15 Lm-2 h-1. The feed was concentrated till the transmembrane pressure reached 3.5 kPa. Diafiltration then commenced using 3 diavolumes. While commencing diafiltration with a smaller feed volume will reduce diluent usage and dilution of the product, it is essential that the transmembrane pressure is not too high to create a compacted low permeability secondary membrane. Here the transmembrane pressure was almost constant at 3.5 kPa during diafiltration. Virus recovery was 94%.

A novel multi-modal anion exchange (MMAEX) membrane with both electrostatic and hydrophobic interaction moieties was developed for the separation of full and empty AAV2 capsids with only slight differences in surface charge and hydrophobicity. Both gradient and two-step elution have been able to separate the full and empty capsids effectively. During gradient elution with slight increase in conductivity coupled with weakening electrostatic and enhanced hydrophobic interactions between the ligand and the capsids, two distinctive elution peaks representing empty and full capsids were resolved. Full capsid recovery of 94 % at 89 % purity has been achieved with a loading density of ∼1012 virus particles per milliliter of membrane volume. During the two-step elution process, the functionalized membrane can achieve 88 % full capsid recovery at 75 % purity, or 67 % recovery at 89 % purity, or 59 % recovery at 93 % purity at first-step conductivity of 7.0, 7.5 and 8.0 mS/cm respectively and a loading density of ∼1013 particles per milliliter of membrane volume. Our results indicate that our MMAEX membrane coupled with careful modulation of capsid-ligand interaction has superior performance for separating the full and empty AAV capsids.

Microcystin-LR (MCLR) is a toxin produced by harmful algal blooms that is emerging as a threat to drinking and recreational water systems worldwide. Nanofiltration (NF) is an effective technique for purifying contaminated water sources; however, membrane fouling caused by coexisting organic matter limits the practicality of the process. This research studies the use of an electrocoagulation (EC) pretreatment to limit fouling during the NF process. Water for this study was taken from Lake Fayetteville, a local body of water where MCLR concentrations have been recorded to be >15 µg/L. EC was performed using polyaluminum chloride as a background electrolyte at various operating conditions. EC-treated water was then further treated with NF to assess the impact of the EC pretreatment on NF fouling. It was found that the larger particle size of the sludge produced using aluminum electrodes at pH 7 had the best combination of settling ability and organic carbon removal (92%). This also led to the smallest flux decline during six-hour NF experiments of just 9%. These results highlight the potential of an EC pretreatment as an antifouling technique for the NF treatment of water contaminated with algal toxins.

Membrane technology offers the potential for low-footprint solutions for industrial separation processes. However, using fabrication has raised sustainability concerns, prompting researchers to seek safer, bio-based solvent alternatives. Further disposal of used membranes is problematic. Both these concerns adversely affect the overall life cycle analysis. Green chemistry principles aim to reduce hazardous substances in chemical applications. Many studies have explored replacing conventional toxic solvents with less harmful green solvents. This opinion article covers the most recent trends, challenges, future directions, and advancements in sustainable membrane manufacturing over the past 4 years. These advances will lead to more sustainable membrane processes.

Technologies for large-scale manufacturing of viral vectors for gene therapies, such as tangential flow filtration and membrane chromatography, are under development. In these early stages of process development, techno-economic analyses are useful for identifying membrane properties yielding the greatest impact on process performance. In this study, we adapted a techno-economic framework used for monoclonal antibody capture for adeno-associated viral vector purification. We added mechanistic models to simulate flux decline during harvesting and separating full and empty capsids during polishing. Graphical user interfaces were added to help users explore the design search space. We selected a base process and manipulated selected variables to see their impact on large-scale manufacturing performance. These sensitivity analyses revealed that, under the selected process conditions, increasing module capacity reduces cost of goods more effectively than increasing operational flux in tangential flow membrane filtration modules for virus harvesting. Membrane chromatography columns with relatively low dynamic binding capacity (DBC) and short residence time (RT) offered similar or better economic performance than those with high DBC and long RT. Additionally, the difference in equilibrium solid-phase concentration between full and empty capsids as a function of salt concentration significantly affects purity.

SPECIALTY GRAND CHALLENGE article Front. Membr. Sci. Technol., 12 January 2024Sec. Membrane Transport, Modeling and Simulation Volume 2 - 2023 | https://doi.org/10.3389/frmst.2023.1357625

Chinese hamster ovary (CHO) cells are among the most common cell lines used for therapeutic protein production. Membrane fouling during bioreactor harvesting is a major limitation for the downstream purification of therapeutic proteins. Host cell proteins (HCP) are the most challenging impurities during downstream purification processes. The present work focuses on identification of HCP foulants during CHO bioreactor harvesting using reverse asymmetrical commercial membrane BioOptimal™ MF-SL. In order to investigate foulants and fouling behavior during cell clarification, for the first time a novel backwash process was developed to effectively elute almost all the HCP and DNA from the fouled membrane filter. The isoelectric points (pIs) and molecular weights (MWs) of major HCP in the bioreactor harvest and fouled on the membrane were successfully characterized using two-dimensional gel electrophoresis (2D SDS-PAGE). In addition, a total of 8 HCP were identified using matrix-assisted laser desorption/ionization-mass spectroscopy (MALDI-MS). The majority of these HCP are enzymes or associated with exosomes, both of which can form submicron-sized particles which could lead to the plugging of the filters.

Efficient extraction of Cs+ from aqueous solution was investigated by liquid-liquid extraction based on ionic liquids (ILs). In this study, Di(aminobenzo)-18-crown-6 (DAB18C6) was used as the extractant and three ILs (1-butyl-3-methylimidazolium hexafluorophosphate ([C(4)mim][PF6]), 1-hexyl-3-methylimidazolium hexafluorophosphate ([C(6)mim][PF6]), and 1-butyl-3-methylimidazolium bis-trifluoromethyl sulfonamide ([C(4)mim][NTf2])) were employed as co-extractants in the construction of a liquid-liquid extraction system for efficient and selective extraction of Cs+ from aqueous solutions. It was demonstrated that the DAB18C6-[C(4)mim][NTf2] mixed solvent system at 0.12 mol/L DAB18C6, a mass ratio of ILs/CHCl3 of 1:4 and a volumetric ratio of O/A of 1:1 exhibited a high % extraction of Cs+ up to 99.94 %, with a higher selectivity for Cs+ relative to coexisting ions such as K+ (beta(Cs/K) = 1216.7) and Rb+ (beta(Cs/Rb) = 139.03). The high selectivity of the extraction system for Cs+ was attributed to the lower hydration binding energy of Cs+ (-366.51 kJ/mol) and the stronger interaction between DAB18C6 and Cs+, g(r) = 12.7. Further, the hydrogen bonding interaction between the amino crown ether and ionic liquid increases the viscosity and surface tension of the extraction system, thus enhancing the stability of the system. Noteworthy, the most stable structure formed by DAB18C6-Cs+-[NTF2](-) is attributed to cation exchange. In summary, this study demonstrates the great potential for efficient separation and extraction of cesium from aqueous solutions.

The hydrolysis of cellulose using ionic liquid (IL) has been extensively studied but there is limited understanding of the removal of IL from the biomass hydrolysate. Finding a suitable method for the recovery and reuse of IL is one of the biggest challenges before its large-scale application. Selecting an appropriate combined recovery process is very important. This study proposed a facile ion-exchange combined method for the recovery of IL from the modeled cellulose hydrolysate mixture containing sugars as well as γ-valerolactone (GVL) via an adsorption–desorption mechanism using sulfonic acid cation-exchange (Amberlyst 15 (H)) resin. The results showed that the resin could adsorb more than 94% of 1-ethyl-3-methylimidazolium chloride [Emim]Cl IL at ambient conditions within a contact time of 20 min. The other coexisting constituents like glucose and GVL have no significant effect on the adsorption efficiency of IL. The adsorption of IL on Amberlyst 15 (H) resin was observed to be pseudo-second-order adsorption. The regeneration of the adsorbed IL was possible up to 70% using low-cost, easily available sodium chloride (NaCl) solution. Similarly, despite the interference of other unwanted byproducts in the real biomass hydrolysate sample, an IL adsorption efficiency up to 51% was reached under similar operating conditions. This study thus opens the facile possibility of extracting and recycling IL used in the biomass hydrolysis process.

The development of an ideal membrane for membrane distillation (MD) is of the utmost importance. Enhancing the efficiency of MD by adding nanoparticles to or onto a membrane’s surface has drawn considerable attention from the scientific community. It is crucial to thoroughly examine state-of-the-art nanomaterials-enabled MD membranes with desirable properties, as they greatly enhance the efficiency and reliability of the MD process. This, in turn, opens up opportunities for achieving a sustainable water–energy–environment nexus. By introducing carbon-based nanomaterials into the membrane’s structure, the membrane gains excellent separation abilities, resistance to various feed waters, and a longer lifespan. Additionally, the use of carbon-based nanomaterials in MD has led to improved membrane performance characteristics such as increased permeability and a reduced fouling propensity. These nanomaterials have also enabled novel membrane capabilities like in situ foulant degradation and localized heat generation. Therefore, this review offers an overview of how the utilization of different carbon-based nanomaterials in membrane synthesis impacts the membrane characteristics, particularly the liquid entry pressure (LEP), hydrophobicity, porosity, and membrane permeability, as well as reduced fouling, thereby advancing the MD technology for water treatment processes. Furthermore, this review also discusses the development, challenges, and research opportunities that arise from these findings.

Even though membranes can lead to more environmentally sustainable separation processes, membrane casting typically involves toxic organic solvents. Recently, there has been increasing interest in substituting these toxic solvents for green solvents. In this study, polysulfone ultrafiltration membranes were fabricated by nonsolvent induced phase separation using two green, bio-derived solvents: Cyrene and gamma-valerolactone (GVL). The effect of coagulation bath composition was investigated, with water, ethanol, and water/ethanol mixtures tested as nonsolvents in the bath. Membranes were characterized and their performance was tested by dead-end filtration. For both Cyrene and GVL, using pure water in the coagulation bath resulted in membranes with residual solvent trapped inside. During dead-end filtration, these membranes were either impermeable (in the case of GVL) or had very low bovine serum albumin (BSA) rejection (in the case of Cyrene). Concentrations of similar to 50-75 v% ethanol in the coagulation bath led to improved solvent removal and better pore formation, as indicated by scanning electron microscopy. These membranes also had higher flux and rejection. For example, membranes cast using Cyrene with a 65:35 volumetric ratio of ethanol:water in the coagulation bath achieved 70.1 L/m(2)/h water flux at 2.41 bar and 96.7 % BSA rejection. Additionally, the effect of humidity on membranes cast using GVL was investigated. Membranes cast under moderate humidity had novel surface morphologies with porous dimples similar to 1 mu m wide. Overall, these results show that Cyrene and GVL are promising solvents for preparing polysulfone ultrafiltration membranes. The work highlights the importance of relating membrane properties to casting conditions.