Cross-flow Filtration Research Articles

DOP032 Extracellular vesicles from Bifidobacterium longum Subspecies infantis attenuate intestinal inflammation via macrophage polarization

Abstract Background Inflammatory Bowel Disease (IBD) is characterized by chronic intestinal inflammation driven by a complex interplay of genetic, environmental, and immune interactions1. Despite significant advancements in IBD therapies, many patients still face challenges in achieving complete remission or maintaining long-term treatment efficacy. We hypothesize that extracellular vesicles from Bifidobacterium longum subspecies infantis (B. infantis-EVs) can regulate immune responses, promote balanced macrophage polarization, and modulate the gut microbiota, ultimately attenuating intestinal inflammation. Methods B. infantis-EVs were isolated via tangential flow filtration (TFF)2. In vitro studies examined cellular morphology, expression of inflammatory cytokines, and immunofluorescence staining of activated RAW 264.7 macrophage cells34. In a 3% dextran sulfate sodium (DSS) mouse model, disease severity was assessed using the Disease Activity Index (DAI), colon length, survival rate, and metagenome analysis. To confirm the targeting capability of B. infantis-EVs for inflamed lesions, cellular uptake was analyzed using confocal microscopy, and biodistribution was assessed with an In Vivo Imaging System (IVIS). Results To investigate the effects of B. infantis-EVs on macrophage polarization, we examined the cellular morphology and macrophage markers of RAW 264.7 cells. B. infantis-EVs suppress macrophage cells from driving an M1-like phenotype, and downregulated M1 markers (iNOS and CD86) while upregulating M2 markers (Arg1 and CD200R) (Fig. 1a-c). They also decreased the expression of LPS-induced pro-inflammatory cytokines (IL-1β, IL-2, IL-6, and TNF-α) while increasing anti-inflammatory cytokines (IL-10 and TGF-β) (Fig. 1d). In vivo, oral administration of B. infantis-EVs mitigated weight loss (p=0.0120), preserved colon length (p=0.0018), reduced DAI (p=0.0079), lowered histological score (p=0.0003), and modulated gut microbiota composition in DSS-treated mice compared to the DSS + PBS groups. Additionally, fluorescence intensities were stronger in the inflamed group treated with Cy5-labeled B. infantis-EVs compared to non-inflamed group at all-time points tested both cellular uptake and biodistribution (Fig. 1e). These findings suggest that B. infantis-EVs have the capability to target inflamed lesions and exhibit significant anti-inflammatory effects. Conclusion In this study, B. infantis-EVs attenuated intestinal inflammation via the modulation of macrophage polarization with its targeting capability to inflamed lesions. B. infantis-EVs could emerge as an innovative and promising therapeutic option for future IBD treatment.

Evaluation of Ceramic Membrane Filtration for Alternatives to Microplastics in Cosmetic Formulations Using FlowCam Analysis.

The rapid expansion of the cosmetics industry has significantly increased the adoption of alternative microplastics in response to increasingly stringent global environmental regulations. This study presents a comparative analysis of the treatment performance of silica powder and cornstarch-common alternatives for microplastics in cosmetics-using ceramic membrane filtration combined with flow imaging microscopy (FlowCam) to analyze particle behavior. Bench-scale crossflow filtration experiments were performed with commercially available alumina ceramic membranes. By analyzing high-resolution images from FlowCam, the transport and retention behaviors of the two microplastic alternatives were examined by comparing their morphological properties. Despite their similar particle sizes, the cornstarch demonstrated a higher removal efficiency (82%) than the silica (72%) in the ceramic membrane filtration due to its greater tendency to aggregate. This increased tendency for aggregation suggests that cornstarch may contribute to faster fouling, while the stability and uniformity of silica particles result in less fouling. The FlowCam analysis revealed that the cornstarch particles experienced a slight increase in circularity and compactness over time, likely due to physical swelling and aggregation, while the silica particles retained their shape and structural integrity. These findings highlight the impact of the morphological properties of alternative microplastics on their filtration behavior and fouling potential.

Critical assessment of purification processes for the robust production of polymeric nanomedicine.

Polymeric nanoparticles are among the most widely used nanocarriers for delivering therapeutic molecules. However, their synthesis processes often generate undesirable impurities that could be toxic and challenging to eliminate. In this study, we compared three purification techniques - centrifugation, dialysis, and tangential flow filtration (TFF) - to evaluate their efficacy in removing residual drug, surfactant, and solvent while preserving the nanoparticles' physicochemical features (hydrodynamic size, zeta potential, polydispersity index). Centrifugation excels in eliminating unencapsulated drug and residual surfactant but significantly affects the nanoparticles' physicochemical properties, such as colloidal stability and size homogeneity. On the other hand, dialysis is a gentler technique effective in removing residual solvent but less so for residual surfactant and unencapsulated drug. TFF emerges as a balanced approach, offering a compromise between the two but none of these techniques achieves satisfactory purification at lab-scale alone. While each technique has its merits, none can meet all requirements independently. The optimal purification strategy often involves a combination of techniques, determined on a case-by-case basis considering factors like purity levels, time, costs, and the preservation of critical properties such as drug loading and colloidal stability. This study underscores the need for a nuanced approach in selecting purification strategies for polymeric nanoparticles in drug delivery applications.

Controlling tangential flow filtration in biomanufacturing processes via machine learning: A literature review

Controlling tangential flow filtration in biomanufacturing processes via machine learning: A literature review

Distinct molecular properties and functions of small EV subpopulations isolated from human umbilical cord MSCs using tangential flow filtration combined with size exclusion chromatography.

As functional derivatives of mesenchymal stem cells (MSCs), small extracellular vesicles (sEVs) have garnered significant attention and application in regenerative medicine. However, the technical limitations for large-scale isolation of sEVs and their heterogeneous nature have added complexity to their applications. It remains unclear if the heterogeneous sEVs represent different aspects of MSCs functions. Here, we provide a method for the large-scale production of sEVs subpopulations derived from human umbilical cord mesenchymal stem cells (HucMSCs), utilizing tangential flow filtration combined with size exclusion chromatography. The resulting subpopulations, S1-sEVs and S2-sEVs, exhibited stable variations in size, membrane-marked proteins, and carrying cargos, thereby displaying distinct functions both in vitro and in animal disease models. S1-sEVs, that highly expressed CD9, HRS and GPC1, demonstrated a greater immunomodulatory impact, while S2-sEVs with enriched expression of CD63 and FLOT1/2 possessed enhanced capacities in promoting cell proliferation and angiogenesis. These discrepancies are attributed to the specific proteins and miRNAs they contain. Further investigation revealed that the two distinct sEVs subpopulations corresponded to different biological processes: the ESCRT pathway (S1-sEVs) and the ESCRT-independent pathway represented by lipid rafts (S2-sEVs). Therefore, we propose the potential for large-scale isolation and purification of sEVs subpopulations from HucMSCs with distinct functions. This approach may provide advantages for targeted therapeutic interventions in various MSC indications.

Single-Pass Tangential Flow Filtration (SPTFF) for Continuous mRNA Concentration and Purification

Single-Pass Tangential Flow Filtration (SPTFF) for Continuous mRNA Concentration and Purification

Dual-Stage Cross-Flow Filtration: Integrated Capture and Purification of Virus-Like Particles.

Virus-like particles (VLPs) are a versatile technology for the targeted delivery of genetic material through packaging and potential surface modifications for directed delivery or immunological issues. Although VLP production is relatively simple as they can be recombinantly produced using microorganisms such as Escherichia coli, their current downstream processing often relies on individually developed purification strategies. Integrating size-selective separation techniques may allow standardized platform processing across VLP purification. This study presents an innovative dual-stage cross-flow filtration (CFF) set-up for integrated capture and purification of VLPs, enabling processing solely based on the size-selective separation techniques precipitation and filtration. The2 μm/300 kDa MWCO membrane configuration allows the seamless integration of selective VLP precipitation, two consecutive diafiltration steps-first, for washing the VLP precipitates in the first membrane stage, and second, for isolating the re-dissolved VLPs by continuously removing precipitant and contaminants in the second membrane stage-and ultrafiltration for setting a target VLP concentration. Compared to a single-stage CFF set-up, this dual-stage CFF set-up with its integrative, automated design demonstrated the capabilities of product accumulation and contaminant handling while maintaining high productivity. Overall, this study represents a significant advancement toward standardized platform processing of protein nanoparticles through precipitation and filtration, and underscores the potential to expand its applicability to diverse biological molecules, unique process conditions, other phase behavior-dependent processes, and continuous processing.

Evaluating the Separation Performance and Efficiency of MF Membranes in Industrial Textile Wastewater Treatment

The rapid growth of the population and industrial development have led to a significant increase in wastewater generation across various sectors. The textile industry stands out as a major contributor to economic growth but also a substantial source of environmental pollution. The typical effluents discharged from textile industries are a complex mixture of dyes, metals, and other pollutants. The presence of high levels of pollutants may overwhelm traditional treatment methods. Therefore, it is necessary to use more advanced techniques such as membrane filtration to treat the wastewater. Membrane technology has recently become famous for wastewater treatment due to its flexibility, high efficiency in removing contaminants, and low energy usage. There are several membrane filtration methods which are extensively used in water treatment procedures, including microfiltration (MF), ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO). In this study, the membrane process investigated the effect of feed pressure using a commercial MF flat sheet membrane on the performance of treatment. The pressure of the feed varies from 2 to 10 bar, with a stepwise increment of 2 bar. The water flux was measured using a cross-flow filtration system, and performance was assessed by calculating the water flux and removal efficiencies for total suspended solids (TSS) and turbidity. The results show that the MF membrane has a high removal efficiency of total suspended solids and turbidity. The removal efficiency of TSS ranged from 87.1% to 96.2%, while the removal efficiency of turbidity ranged from 91.2% to 93.7%.

Effects of Preparation Conditions on Performance of PES:PEG Flat Sheet Membrane for MG Dye Separation

This study deals with the morphology and performance properties of a novel thin flat sheet ultrafiltration membrane; Malachite Green (MG) dye filtration behavior was evaluated in the cross-flow filtration system. The prepared membranes included the incorporation of 16 wt. % of polyether sulfone (PES)/DMF and 5 wt.% of Polyethylene Glycol (PEG) via the phase inversion process. Adding PEG decreased the internal concentration polarization, improved the membrane hydrophilicity, changed pore morphologies, and enhanced membrane performance. The SEM and AFM tests were used to characterize the composition and structure of the membrane. With different casting conditions, the membrane shape changed. The effect of membrane thickness (100, 150, and 200) µm and coagulation bath properties temperature (15, 25, and 35) °C and composition DMF (10, 20, 30 %) in water on the fabricated membrane were investigated. To evaluate the membrane filtration performance, the fabricated membranes were applied in an ultrafiltration system to treat Malachite Green dye solution at a concentration of (10 ppm) as a model pollutant. Based on the obtained results, the ideal membrane parameters were150 µm in thickness, 35°C in temperature, and 10% in composition DMF; the removal efficiency was observed to be (94.5%, 93%, and 99.5%) while the permeate flux (45, 35 and 30) LMH, respectively.

Post-docking hydrophilic Ag-MOF-303 filled in TFC for nanofiltration of charged PhACs in water

Modifying membrane pore size and surface charge to enhance nanofiltration selectivity presents a crucial challenge in managing pollutants with varying charge properties. This study introduces Ag-MOF-303, synthesized by incorporating Ag into hydrophilic MOF-303 through molecular docking, effectively reducing the pore size to the nanofiltration scale. Subsequently, Ag-MOF-303 was deposited onto a PVDF substrate via interfacial polymerization, forming thin-film composite (TFC) polyamide membranes with enhanced selectivity and permeability. Notably, Ag-MOF-303@PVDF is positively charged, enabling the removal of differently charged pollutants from water. Structure-activity analysis confirmed the effective construction of the functional layer, where the Al3+ and Ag+ content significantly influenced the membrane’s charge properties. Cross-flow filtration experiments revealed a permeability of 14 L·m−2·h−1·bar−1 for Ag-MOF-3030.2%@PVDF, achieving rejection rates exceeding 90 % for CaCl2 and MgSO4 due to the Donnan effect. The membrane showed notable selective removal of six pharmaceutically active compounds with varying charges, maintaining a selectivity coefficient around 70, driven by the combined effects of Donnan exclusion and size sieving. Moreover, Ag-MOF-3030.2%@PVDF displayed stable pore size at 0.4 nm, achieving over 80 % flux recovery after protein and lysozyme fouling, thereby enhancing antifouling and antibacterial properties. This novel strategy of utilizing hydrophilic MOF-303, modified via molecular docking to reduce pore size for the nanofiltration of variously charged micropollutants, provides valuable insights into MOF post-modification techniques and the separation mechanisms in nanofiltration, thereby expanding the application potential of positively charged nanofiltration membranes.

Permeability–selectivity trade-off for a universal leaky channel inspired by mobula filters

Mobula rays have evolved leaf-shaped filter structures to separate food particles from seawater, which function similarly to industrial cross-flow filters. Unlike cross-flow filtration, where permeability and selectivity are rationally designed following trade-off analyses, the driving forces underlying the evolution of mobula filter geometry have remained elusive. To bridge the principles of cross-flow and mobula filtration, we establish a universal framework for the permeability–selectivity trade-off in a leaky channel inspired by mobula filters, where permeability and selectivity are characterized by the pore-scale leaking rate and the cut-off particle size, respectively. Beyond the classic pore-flow regime in cross-flow filtration, we reveal transition and vortex regimes pertinent to mobula filtration. Combining theory, physical experiments, and simulations, we present distinct features of water permeability and particle selectivity across the three regimes. In particular, we identify an unreported 1/2-scaling law for the leaking rate in the vortex regime. We conclude by demonstrating that mobula filters strike an elegant balance between permeability and selectivity, which enables mobula rays to simultaneously satisfy biological requirements for breathing and filter feeding. By integrating cross-flow and mobula filtration into a universal framework, our findings provide fundamental insights into the physical constraints and evolutionary pressures associated with biological filtration geometries and lay the foundation for developing mobula-inspired filtration in industry.

Anhydrous interfacial polymerization induced by isopropanol to construct high permeance polyamide membranes for organic solvent nanofiltration

Highly permeable polyamide (PA) membranes with precise molecular sieving capabilities are crucial for energy-efficient chemical separations. There is a critical need to design solvent-stabilized membranes with enhanced permeance to improve separation efficiency. In this work, we propose a novel anhydrous interfacial polymerization (IP) method, where flexible polyethyleneimine (PEI) and rigid p-phenylenediamine (PPD) are uniquely dissolved in isopropanol (IPA) and subsequently crosslinked with trimethyl chloride (TMC) in situ to fabricate high-performance PA membranes. Notably, the use of IPA as a solvent represents a significant advancement in membrane fabrication. This approach resulted in PA membranes with a relatively loose selective layer compared to traditional PA membranes, allowing for exceptionally high solvent permeance while maintaining strong rejection performance in organic solvent nanofiltration (OSN). The obtained PEI + PPD/TMC PA membranes demonstrated outstanding ethanol (EtOH) permeance of 46.44 L m−2 h−1 bar−1 in the organic solvent system, along with good rejection for small organic molecules, such as 93.84% for Eriochrome Black T (EBT, 461.38 Da). In addition, the performance of the PEI + PPD/TMC PA membranes remained at a high level even during 510 min of continuous cross-flow filtration, under high pressure (5 bar) testing, and after 6 cycles of separation, which demonstrated their good stability in long-term service. This work establishes a robust foundation for employing anhydrous IP reactions and innovative solvent systems, such as IPA, to develop high-permeance PA membranes.

Abstract 4119680: First-in-Man Treatment of Heart Failure by Repeated Intravenous Infusions of a Cardiovascular Cell-Derived Extracellular Vesicle-Enriched Secretome

Background: Most of the effects of intramyocardially transplanted stem cells can be duplicated by the sole administration of their secretome but this approach has not yet been tested in heart failure (HF). Methods: The SECRET-HF phase I trial (NCT05774509) was designed according to a Bayesian optimal interval scheme to assess the effects of repeated intravenous infusions of a cellular secretome in 12 patients with a non-ischemic dilated cardiomyopathy. The main inclusion criteria are severe symptoms (NYHA Class III despite an optimal guideline-directed medical therapy), a reduced left ventricular (LV) ejection fraction (EF ≤40%) and ineligibility for a heart transplant. The Investigational Medicinal Product was derived from human induced pluripotent stem cells reprogrammed from a healthy donor and differentiated in cardiovascular progenitor cells (CPC). Following CPC culture in a dedicated "vesiculation" medium, the conditioned media were collected, filtered, enriched for extracellular vesicles, concentrated by tangential flow filtration and scaled out into glass vials stored at -80°C. Quality controls were implemented throughout the whole process which was conducted according to current Good Manufacturing Practices. Results: Three patients, out of the 4 of the initial low-dose cohort, have now been treated. All had been previously fitted with an automatic internal cardioverter defibrillator (AICD). The secretome was delivered intravenously 3 times, 3 weeks apart, at a dose of 20 x10 9 particles/kg for each infusion. By November, 2024, the follow-up will be 16, 9, 6 and 2 months for each of them (mean: 8 months). So far, none of the treated patients has experienced a dose-limiting toxicity; in particular, there have been no post-treatments ventricular arrhythmia detected by the AICD, no allo-immunization and no inflammation based on the enumeration of lymphocyte subpopulations by flow cytometry. At 6 months, the first patient improved to NYHA Class II with a decrease in echographic LVEDV and LVESV (from 108 mL/m 2 to 87 mL/m 2 and from 80 mL/m 2 to 60 mL/m 2 , respectively) and a concomitant increase in LVEF from 25% to 32%. At 1 month post-treatment, the second patient also reports a symptomatic improvement (NYHA Class II) with an increase in EF from 21% to 28%. Conclusions: This initial experience supports the safety of repeated intravenous administrations of a cardiovascular cellular secretome as a potential noninvasive and user-friendly treatment of severe HF.

Structure-performance relationship in tailored poly(amide-sulfone) membranes for desalination

Poly(amide-sulfone)s were considered the missing link for water desalination membranes, owing to their exceptional properties resulting from the synergism effects of two amide and sulfone structures. To achieve this, a sulfone-based diamine was first synthesized by reacting 4,4′-dichlorodiphenyl sulfone with 3-aminophenol. Subsequently, alternative copolymers of poly(amide-sulfone) were prepared via polycondensation reactions of the synthesized diamine monomer and various diacid chlorides including adipoyl dichloride, isophthaloyl dichloride, and terephthaloyl dichloride. The chemical structures were approved using Fourier transform infrared spectroscopy and hydrogen nuclear magnetic resonance spectroscopy. Porous membranes of the polymers as substrates were prepared by solution casting and phase-inversion method. To form thin film composite membranes, a thin polyamide layer was created through interfacial polymerization on the top surface of prepared substrates using m-phenylenediamine and trimesoyl chloride. After characterization, the performance of all membranes was assessed by evaluating pure water flux, NaCl rejection, and flux recovery ratio using a cross-flow filtration system. The impact of the amide group within the poly(amide-sulfone) substrate structure on thin-film efficiency was explored. Results, revealed that the structure significantly influenced membrane performance. Specifically, the highest pure water flux was 549.50 L.m−2.h−1. Also, NaCl rejection of 98.27 % and flux recovery ratio of 94.21 % were observed among them at pressure of 10 bar. This study provided valuable insights for developing novel poly(amide-sulfone) membranes tailored for desalination applications.

Neural stem cell-derived extracellular vesicles purified by monolith chromatography retain stimulatory effect on in vitro scratch assay.

BackgroundExtracellular vesicles (EVs) have gained traction as potential cell-free therapeutic candidates. Development of purification methods that are scalable and robust is a major focus of EV research. Yet, there is still little in the literature which evaluates purification methods against potency of the EV product. AimsIn the present study, we examine two monolith chromatography methods with a focus on assessing the ability of purified EVs to retain stimulatory effects on firbroblasts to connect scalable purification methods with product outputs. MethodsWe characterised EVs recovered from CTX0E03 (CTX) neural stem cell-conditioned medium in terms of biomarker distribution, functional capacity, and purity. We evaluated the ability of EVs to promote wound closure in an in vitro scratch assay prior to, and following two monolith chromatography steps (anion exchange, and hydrophobic interaction) to determine whether these options may better serve EV bioprocessing. ResultsEVs from CTX cells were successful in initiating wound repair on a fibroblast scratch assay over 72 hours with a single 20μg dose. EV preparations presented the markers CD9, CD81, CD63, but also contained culture albumin and DNA as process impurities. EVs recovered by tangential flow filtration could be successfully purified further by both monolith chromatography steps. Post-monolith EV stimulation was conserved. ConclusionThe results indicate that monolith chromatography is a viable purification method for EVs derived from cell culture that doesn't detract from the product's ability to stimulate fibroblasts, suggesting that product functionality is conserved. Further work is needed in developing suitable downstream processes and analytics to achieve clinically relevant purities for injectable biologics.

An Experimental and Modeling Approach to Study Tangential Flow Filtration Performance for mRNA Drug Substance Purification.

Following the recent COVID-19 pandemic, mRNA manufacturing processes are being actively developed and optimized to produce the next generation of mRNA vaccines and therapeutics. Herein, the performance of the tangential flow filtration (TFF) was evaluated for high-recovery, and high-purity separation of mRNA from unreacted nucleoside triphosphates (NTPs) from the in vitro transcription (IVT) reaction mixture.For the first time, the fouling modelwas successfully validated with TFF experimentaldata to describe the adsorption of mRNA on filtration membrane. The fouling model enables monitoring of the mRNA purification processes, designing an appropriate strategy for filter clean-up, replacing the column at the right time and reducing the process cost. Recovery greater than 70% mRNA without degradation was obtained by implementing a capacity load of ∼19g/m2, <2.5psi transmembrane pressure (TMP) and feed flux of 300 LMH.This approach also enables the purification of multiple mRNA drug substance sequences for the treatment of a wide range of different diseases.

Fabrication and optimization of parameters of high-performance polyamide thin film composite membranes for desalination

Abstract Herein, we report the synthesis of polyamide thin film composite (PA-TFC) membranes through interfacial polymerization (IP) using an aqueous solution of diaminodiphenylmethane (DDM) and terephthaloyl chloride (TPC) in n-hexane, onto polysulfone (PSF) surface. The synthesized membranes were characterized by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscope (SEM) and contact angle measurement. To optimize the conditions for achieving a better membrane function, desalination (%) and permeate flow rate (L/m2.h.bar) were evaluated as a function of synthesis conditions. The membrane efficiency for salt rejection was evaluated against NaCl using a bench-top cross-flow filtration assembly where the membrane showed up to 73.13% salt rejections of NaCl. While, the salt rejection of Na2SO4 and MgSO4 were showed up to 84.92% and 82.94%. The promising synthesized membranes exhibited a permeate flux of 41.7 L/m2.hr.bar. The contact angle analysis revealed that the synthesized PA-TFC membranes are hydrophilic as the value of contact angle measured as 109°-100°. The synthesized membrane offered facile and effective access for the synthesis of high-performance PA-TFC membranes.

Scalable Production and Biophysical Characterization of High-Molecular-Weight Relaxed and Tense Quaternary State Polymerized Human Hemoglobin as Potential Red Blood Cell Substitutes.

High-molecular-weight (HMW) (>500 kDa) glutaraldehyde-polymerized human hemoglobin (PolyhHb) is a promising hemoglobin-based oxygen carrier (HBOC) due to its decreased risk of vasoconstriction and oxidative tissue injury. Previously, HMW tense (T) quaternary state PolyhHb was synthesized at the pilot scale with tangential flow filtration (TFF) for the removal of low-molecular-weight species. However, T-state PolyhHb is limited to specific biomedical applications due to its low oxygen affinity, thus motivating the need to produce high oxygen affinity relaxed (R) quaternary state PolyhHb at the pilot scale. This study explored the pilot-scale synthesis and extensive biophysical characterization of both HMW T- and R-state PolyhHb. The resultant characterization demonstrated the successful synthesis of low and high oxygen affinity PolyhHb with increased molecular weight (∼1000-1500 kDa). Overall, T- and R-state PolyhHb provides a platform for manufacturing oxygen therapeutics with a diverse range of oxygen affinities and potential biomedical applications.

Particulate fouling simulation in unit micropore using a hydrodynamically coupled Lagrangian framework

Predicting and mitigating pore clogging is challenging for the sustainable operation of water treatment systems. During transport and filtration through membrane micropores, buoyant contaminants in water gradually deposit on the surface, reducing the membrane's lifespan and performance, and sometimes completely blocking the pores. To alleviate the negative effects of fouling and to ensure sustainable operation, it is necessary to understand the fundamental mechanisms of fouling and to predict the probability of fouling formation under specific geometrical and material conditions. In this study, multiscale simulations are conducted to understand the fundamental mechanisms of particulate fouling at a microscopic level based on a Lagrangian framework incorporating inter-particle hydrodynamic interactions. We investigate both dead-end and cross-flow filtration, considering the direction of the feed stream relative to the unit micropore. The results elucidate the quantitative background of fouling history, which agrees with experimental findings. Depending on the level of hydrodynamic stress specific to the clog location and the nature of inter-particle interactions, deformation or resuspension of the clog is observed, competing with deposition, which leads to a two-way fouling history. Dominant deposition leads to micropore clogging, and to the best of the authors' knowledge, this is the first study to observe complete blockage and subsequent reopening. With this approach, the microscopic backgrounds between permanent and temporary pore blocking are distinguished. This study is expected to provide useful insights for controlling operational conditions to optimize anti-fouling performance in the transport and filtration through micropores.

Heterogeneous Covalent Organic Framework Membranes Mediated by Polycations for Efficient Ions Separation.

Precise ions sieving at angstrom-scale is gaining tremendous attention thanks to its significant impact at the water-energy nexus. Herein, a novel polycation-modulated interfacial polymerization (IP) strategy is developed to prepare a heterogeneously charged covalent organic frameworks (COFs) membrane. Cationic poly(diallyldimethylammonium chloride) (PDDA) regulates the growth and assembly of anionic COFs nanosheets, which thus provides a negative, smooth top surface and positive, rough bottom surface, indicating the presence of heterogeneously charged angstrom-scale channels through the membrane. Experiments and simulations are conducted to understand the facilitated ions transport behavior relative to specific interactions raised by heterogeneously charged channels and angstrom-scale steric hinderance as well, rendering the membrane with robust mono-/divalent cations sieving capabilities. The selectivity (61.6) of Li+ to Mg2+ in mixed saline under the continuous cross-flow filtration mode is superior to most of the reported nanofiltration membranes. This polycation-mediated interfacial polymerization strategy offers a compelling opportunity to develop versatile heterogeneously charged COF membranes for exquisite ion sieving.