Effect of Membrane Permeance and System Parameters on the Removal of Protein-Bound Uremic Toxins in Hemodialysis.

Inadequate clearance of protein-bound uremic toxins (PBUTs) during dialysis is associated with morbidities in chronic kidney disease patients. The development of high-permeance membranes made from materials such as graphene raises the question whether they could enable the design of dialyzers with improved PBUT clearance. Here, we develop device-level and multi-compartment (body) system-level models that account for PBUT-albumin binding (specifically indoxyl sulfate and p-cresyl sulfate) and diffusive and convective transport of toxins to investigate how the overall membrane permeance (or area) and system parameters including flow rates and ultrafiltration affect PBUT clearance in hemodialysis. Our simulation results indicate that, in contrast to urea clearance, PBUT clearance in current dialyzers is mass-transfer limited: Assuming that the membrane resistance is dominant, raising PBUT permeance from 3 × 10-6 to 10-5 m s-1 (or equivalently, 3.3 × increase in membrane area from ~ 2 to ~ 6 m2) increases PBUT removal by 48% (from 22 to 33%, i.e., ~ 0.15 to ~ 0.22 g per session), whereas increasing dialysate flow rates or adding adsorptive species have no substantial impact on PBUT removal unless permeance is above ~ 10-5 m s-1. Our results guide the future development of membranes, dialyzers, and operational parameters that could enhance PBUT clearance and improve patient outcomes.

Cascaded compression of size distribution of nanopores in monolayer graphene.

Monolayer graphene with nanometre-scale pores, atomically thin thickness and remarkable mechanical properties provides wide-ranging opportunities for applications in ion and molecular separations1, energy storage2 and electronics3. Because the performance of these applications relies heavily on the size of the nanopores, it is desirable to design and engineer with precision a suitable nanopore size with narrow size distributions. However, conventional top-down processes often yield log-normal distributions with long tails, particularly at the sub-nanometre scale4. Moreover, the size distribution and density of the nanopores are often intrinsically intercorrelated, leading to a trade-off between the two that substantially limits their applications5-9. Here we report a cascaded compression approach to narrowing the size distribution of nanopores with left skewness and ultrasmall tail deviation, while keeping the density of nanopores increasing at each compression cycle. The formation of nanopores is split into many small steps, in each of which the size distribution of all the existing nanopores is compressed by a combination of shrinkage and expansion and, at the same time as expansion, a new batch of nanopores is created, leading to increased nanopore density by each cycle. As a result, high-density nanopores in monolayer graphene with a left-skewed, short-tail size distribution are obtained that show ultrafast and ångström-size-tunable selective transport of ions and molecules, breaking the limitation of the conventional log-normal size distribution9,10. This method allows for independent control of several metrics of the generated nanopores, including the density, mean diameter, standard deviation and skewness of the size distribution, which will lead to the next leap in nanotechnology.

More than magnetic isolation: Dynabeads as strong Raman reporters towards simultaneous capture and identification of targets.

Dynabeads are superparamagnetic particles used for immunomagnetic purification of cells and biomolecules. Post-capture, however, target identification relies on tedious culturing, fluorescence staining and/or target amplification. Raman spectroscopy presents a rapid detection alternative, but current implementations target cells themselves with weak Raman signals. We present antibody-coated Dynabeads as strong Raman reporter labels whose effect can be considered a Raman parallel of immunofluorescent probes. Recent developments in techniques for separating target-bound Dynabeads from unbound Dynabeads makes such an implementation feasible with high specificity. We deploy Dynabeads anti-Salmonella to bind and identify Salmonella enterica, a major foodborne pathogen. Dynabeads present major peaks around 1000 and 1600 cm-1 from aliphatic and aromatic C-C stretching of the polystyrene coating and near 1350 cm-1 from the É£-Fe2O3 and Fe3O4 core, confirmed with electron dispersive X-ray (EDX) imaging. Minor to no contributions are made from the surface antibodies themselves as confirmed by Raman analysis of surface-activated, antibody-free beads. Dynabeads' Raman signature can be measured in dry and liquid samples even at single shot ~30 × 30 µm area imaging using 0.5 s, 7 mW laser acquisition with single and clustered beads providing a 44- and 68-fold larger Raman intensity compared to signature from cells. Higher polystyrene and iron oxide content in clusters yields larger signal intensity and conjugation to bacteria strengthens clustering as a bacterium can bind to more than one bead as observed via transmission electron microscopy (TEM). Our findings shed light on the intrinsic Raman reporter nature of Dynabeads. When combined with emerging techniques for the separation of target-bound Dynabeads from unbound Dynabeads such as using centrifugation through a density media bi-layer, they have potential to demonstrate their dual function for target isolation and detection without tedious staining steps or unique plasmonic substrate engineering, advancing their applications in heterogeneous samples like food, water, and blood.

Molecular Self-Assembly Enables Tuning of Nanopores in Atomically Thin Graphene Membranes for Highly Selective Transport.

Atomically thin membranes comprising nanopores in a 2D material promise to surpass the performance of polymeric membranes in several critical applications, including water purification, chemical and gas separations, and energy harvesting. However, fabrication of membranes with precise pore size distributions that provide exceptionally high selectivity and permeance in a scalable framework remains an outstanding challenge. Circumventing these constraints, here, a platform technology is developed that harnesses the ability of oppositely charged polyelectrolytes to self-assemble preferentially across larger, relatively leaky atomically thin nanopores by exploiting the lower steric hindrance of such larger pores to molecular interactions across the pores. By selectively tightening the pore size distribution in this manner, self-assembly of oppositely charged polyelectrolytes simultaneously introduced on opposite sides of nanoporous graphene membranes is demonstrated to discriminate between nanopores to seal non-selective transport channels, while minimally compromising smaller, water-selective pores, thereby remarkably attenuating solute leakage. This improved membrane selectivity enables desalination across centimeter-scale nanoporous graphene with 99.7% and >90% rejection of MgSO4 and NaCl, respectively, under forward osmosis. These findings provide a versatile strategy to augment the performance of nanoporous atomically thin membranes and present intriguing possibilities of controlling reactions across 2D materials via exclusive exploitation of pore size-dependent intermolecular interactions.

Nonlinear ion transport mediated by induced charge in ultrathin nanoporous membranes.

Ultrathin membranes with nanoporous conduits show promise for ionic separations and desalination applications, but the mechanisms underlying the nonlinear ionic transport observed in these systems are not well understood. Here, we demonstrate how induced charge at membrane interfaces can lead to nonlinear ionic transport and voltage-dependent conductance through such channels. The application of an electric field on a polarizable membrane leads to induced charges at the membrane interfaces. The induced charges in turn are screened by diffuse charges in the electrolyte, which are acted upon by the electric field. For extremely thin membranes, the induced charge effect can be significant even for moderate applied voltages commonly used in experiments. We apply a continuum Poisson-Nernst-Planck model to characterize the current-voltage behavior of ultrathin membranes over a wide parameter space. The predictions of the model are compared to recent experiments on graphene and MoS_{2} membranes in an electric field. We expect the role of induced charge to be especially pronounced in the limit of atomically thin membranes.

Monolayer graphene membranes for molecular separation in high-temperature harsh organic solvents.

The excellent thermal and chemical stability of monolayer graphene makes it an ideal material for separations at high temperatures and in harsh organic solvents. Here, based on understanding of solvent permeation through nanoporous graphene via molecular dynamics simulation, a resistance model was established to guide the design of a defect-tolerant graphene composite membrane consisting of monolayer graphene on a porous supporting substrate. Guided by the model, we experimentally engineered polyimide (PI) supporting substrates with appropriate pore size, permeance, and excellent solvent resistance and investigated transport across the resulting graphene-covered membranes. The cross-linked PI substrate could effectively mitigate the impacts of leakage through defects across graphene to allow selective transport without defect sealing. The graphene-covered membrane showed pure solvent permeance of 24.1 L m-2 h-1 bar-1 and stable rejection (∼90%) of Allura Red AC (496.42 g mol-1) in a harsh polar solvent, dimethylformamide (DMF), at 100 °C for 10 d.

Highly porous nanofiber-supported monolayer graphene membranes for ultrafast organic solvent nanofiltration.

Scalable fabrication of monolayer graphene membrane on porous supports is key to realizing practical applications of atomically thin membranes, but it is technologically challenging. Here, we demonstrate a facile and versatile electrospinning approach to realize nanoporous graphene membranes on different polymeric supports with high porosity for efficient diffusion- and pressure-driven separations. The conductive graphene works as an excellent receptor for deposition of highly porous nanofibers during electrospinning, thereby enabling direct attachment of graphene to the support. A universal "binder" additive is shown to enhance adhesion between the graphene layer and polymeric supports, resulting in high graphene coverage on nanofibers made from different polymers. After defect sealing and oxygen plasma treatment, the resulting nanoporous membranes demonstrate record-high performances in dialysis and organic solvent nanofiltration, with a pure ethanol permeance of 156.8 liters m−2 hour−1 bar−1 and 94.5% rejection to Rose Bengal (1011 g mol−1) that surpasses the permeability-selectivity trade-off.

Rapid screening of nanopore candidates in nanoporous single-layer graphene for selective separations using molecular visualization and interatomic potentials.

Nanoporous single-layer graphene is promising as an ideal membrane because of its extreme thinness, chemical resistance, and mechanical strength, provided that selective nanopores are successfully incorporated. However, screening and understanding the transport characteristics of the large number of possible pores in graphene are limited by the high computational requirements of molecular dynamics (MD) simulations and the difficulty in experimentally characterizing pores of known structures. MD simulations cannot readily simulate the large number of pores that are encountered in actual membranes to predict transport, and given the huge variety of possible pores, it is hard to narrow down which pores to simulate. Here, we report alternative routes to rapidly screen molecules and nanopores with negligible computational requirement to shortlist selective nanopore candidates. Through the 3D representation and visualization of the pores' and molecules' atoms with their van der Waals radii using open-source software, we could identify suitable C-passivated nanopores for both gas- and liquid-phase separation while accounting for the pore and molecule shapes. The method was validated by simulations reported in the literature and was applied to study the mass transport behavior across a given distribution of nanopores. We also designed a second method that accounts for Lennard-Jones and electrostatic interactions between atoms to screen selective non-C-passivated nanopores for gas separations. Overall, these visualization methods can reduce the computational requirements for pore screening and speed up selective pore identification for subsequent detailed MD simulations and guide the experimental design and interpretation of transport measurements in nanoporous atomically thin membranes.

Molecular size-dependent subcontinuum solvent permeation and ultrafast nanofiltration across nanoporous graphene membranes.

Selective solvent and solute transport across nanopores is fundamental to membrane separations, yet it remains poorly understood, especially for non-aqueous systems. Here, we design a chemically robust nanoporous graphene membrane and study molecular transport in various organic liquids under subnanometre confinement. We show that the nature of the solvent can modulate solute diffusion across graphene nanopores, and that breakdown of continuum flow occurs when pore size approaches the solvent's smallest molecular cross-section. By holistically engineering membrane support, modelling pore creation and defect management, high rejection and ultrafast organic solvent nanofiltration of dye molecules and separation of hexane isomers are achieved. The membranes exhibit stable fluxes across a range of solvents, consistent with flow across rigid pores whose size is independent of the solvent. These results demonstrate that nanoporous graphene is a rich materials system for controlling subcontinuum flow that could enable new membranes for a range of challenging separation needs.

Iron oxide xerogels for improved water quality monitoring of arsenic(III) in resource-limited environments via solid-phase extraction, preservation, storage, transportation, and analysis of trace contaminants (SEPSTAT).

Arsenic is a widespread trace groundwater contaminant that presents a range of health risks and has an acceptable level of only 10 µg L-1 in drinking water. However, in many countries arsenic quantification in water is limited to centralized laboratories because it requires the use of elemental analysis techniques with high capital cost. As a result, routine water samples are frequently not tested for trace contaminants such as arsenic. In order to facilitate improved arsenic monitoring, we present the use of iron oxide xerogels for adsorption of arsenic(iii) from water samples at neutral pH, dry storage for over 120 days, and desorption of stored arsenic at elevated pH. Iron oxide xerogels offer high surface area (340 m2 g-1) and an As(iii) adsorption capacity of 165 mg g-1. Using an extraction solution of 100 mM sodium hydroxide and 1 mM sodium phosphate, As(iii) is reliably eluted from iron oxide xerogels for initial As(iii) concentrations from 10 µg L-1 to 1000 µg L-1, with a calculated detection limit of less than 4 µg L-1 and less than 17% difference in recovered As(iii) between test solutions with low and high interfering ion concentrations. By demonstrating the ability for iron oxide xerogels to reliably adsorb, store, and release arsenic, we enable the development of protocols for solid-phase extraction, preservation, storage, transportation, and analysis of trace contaminants (SEPSTAT), where arsenic would be adsorbed from water samples onto xerogel-based sorbents and shipped to centralized laboratories for recovery and quantification.

Engineering and characterization of gymnosperm sapwood toward enabling the design of water filtration devices.

Naturally-occurring membranes in the xylem tissue of gymnosperm sapwood enable its use as an abundantly-available material to construct filters, with potential to facilitate access to safe drinking water in resource-constrained settings. However, the material's behavior as a filter is poorly understood, and challenges such as short shelf life have not been addressed. Here, we characterize the operational attributes of xylem filters and show that the material exhibits a highly non-linear dependence of flow resistance on thickness upon drying, and a tendency for self-blocking. We develop guidelines for the design and fabrication of xylem filters, demonstrate gravity-operated filters with shelf life >2 years, and show that the filters can provide >3 log removal of E. coli, MS-2 phage, and rotavirus from synthetic test waters and coliform bacteria from contaminated spring, tap, and ground waters. Through interviews and workshops in India, we use a user-centric approach to design a prototype filtration device with daily- to weekly-replaceable xylem filters, and uncover indicators of social acceptance of xylem as a natural water filter. Our work enhances the understanding of xylem as a filtration material, and opens opportunities for engineering a diverse range of low-cost, biodegradable xylem-based filtration products on a global scale.

Author Correction: High permeability sub-nanometre sieve composite MoS2 membranes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

High permeability sub-nanometre sieve composite MoS2 membranes.

Two-dimensional membranes have gained enormous interest due to their potential to deliver precision filtration of species with performance that can challenge current desalination membrane platforms. Molybdenum disulfide (MoS2) laminar membranes have recently demonstrated superior stability in aqueous environment to their extensively-studied analogs graphene-based membranes; however, challenges such as low ion rejection for high salinity water, low water flux, and low stability over time delay their potential adoption as a viable technology. Here, we report composite laminate multilayer MoS2 membranes with stacked heterodimensional one- to two-layer-thick porous nanosheets and nanodisks. These membranes have a multimodal porous network structure with tunable surface charge, pore size, and interlayer spacing. In forward osmosis, our membranes reject more than 99% of salts at high salinities and, in reverse osmosis, small-molecule organic dyes and salts are efficiently filtered. Finally, our membranes stably operate for over a month, implying their potential for use in commercial water purification applications.

Solid-Phase Extraction, Preservation, Storage, Transport, and Analysis of Trace Contaminants for Water Quality Monitoring of Heavy Metals.

Accurate quantification of trace contaminants currently requires collection, preservation, and transportation of large volumes (250-1000 mL) of water to centralized laboratories, which impedes monitoring of trace-level pollutants in many resource-limited environments. To overcome this logistical challenge, we propose a new paradigm for trace contaminant monitoring based on dry preservation: solid-phase extraction, preservation, storage, transport, and analysis of trace contaminants (SEPSTAT). We show that a few grams of low-cost, commercially available cation exchange resin can be repurposed to extract heavy metal cations from water samples even in the presence of background ions, dryly preserve these cations for at least 24 months, and release them by acid elution for accurate quantification. A compact, human-powered device incorporating the sorbent removes spiked contaminants from real water samples in a few minutes. The device can be stored and transported easily and produces a sample suitable for measurement by standard methods, predicting the original sample heavy metal concentration generally within an error of 15%. These results suggest that, by facilitating the collection, storage, handling, and transportation of water samples and by enabling cost-effective use of high-throughput capital-intensive instruments, SEPSTAT has the potential to increase the ease and reach of water quality monitoring of trace contaminants.

Fieldwork-based determination of design priorities for point-of-use drinking water quality sensors for use in resource-limited environments.

Improved capabilities in microfluidics, electrochemistry, and portable assays have resulted in the development of a wide range of point-of-use sensors intended for environmental, medical, and agricultural applications in resource-limited environments of developing countries. However, these devices are frequently developed without direct interaction with their often-remote intended user base, creating the potential for a disconnect between users' actual needs and those perceived by sensor developers. As different analytical techniques have inherent strengths and limitations, effective measurement solution development requires determination of desired sensor attributes early in the development process. In this work, we present our findings on design priorities for point-of-use microbial water sensors based on fieldwork in rural India, as well as a guide to fieldwork methodologies for determining desired sensor attributes. We utilized group design workshops for initial identification of design priorities, and then conducted choice-based conjoint analysis interviews for quantification of user preferences among these priorities. We found the highest user preference for integrated reporting of contaminant concentration and recommended actions, as well as significant preferences for mostly reusable sensor architectures, same-day results, and combined ingredients. These findings serve as a framework for future microbial sensor development and a guide for fieldwork-based understanding of user needs.

Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective.

HYPOTHESIS: In conventional 'bulk' nanoprecipitation, the capacity to load hydrophobic drugs into the polymeric nanoparticles (NPs) is limited to about 1%. The size distribution of the resulting NPs becomes polydisperse when higher precursor concentration is used to increase the drug loading. Hence, it should be possible to enhance the hydrophobic drug loading in polymeric NPs while maintaining the uniform NP size distribution by optimizing the nanoprecipitation process and purification process. EXPERIMENTS: Systematic studies were performed to enhance the loading of docetaxel (Dtxl) by using a process of centrifugal spin-down, rapid mixing by turbulence, and addition of co-solvent. The size distributions and Dtxl loading of the NPs were measured using dynamic light scattering and HPLC, respectively. FINDINGS: The centrifugal spin-down process helps to maintain uniform size distribution even at the high precursor concentration. In bulk nanoprecipitation, the resulting NPs achieved Dtxl loading up to 3.2%. By adopting turbulence for rapid mixing, the loading of Dtxl increased to 4.4%. By adding hexane as co-solvent, the loading of Dtxl further increased to 5.5%. Because of the drug loading augmentation, high degree of control, and extremely high production rate, the developed method may be useful for industrial-scale production of personalized nanomedicines by nanoprecipitation.

Facile Fabrication of Large-Area Atomically Thin Membranes by Direct Synthesis of Graphene with Nanoscale Porosity.

Direct synthesis of graphene with well-defined nanoscale pores over large areas can transform the fabrication of nanoporous atomically thin membranes (NATMs) and greatly enhance their potential for practical applications. However, scalable bottom-up synthesis of continuous sheets of nanoporous graphene that maintain integrity over large areas has not been demonstrated. Here, it is shown that a simple reduction in temperature during chemical vapor deposition (CVD) on Cu induces in-situ formation of nanoscale defects (≤2-3 nm) in the graphene lattice, enabling direct and scalable synthesis of nanoporous monolayer graphene. By solution-casting of hierarchically porous polyether sulfone supports on the as-grown nanoporous CVD graphene, large-area (>5 cm2 ) NATMs for dialysis applications are demonstrated. The synthesized NATMs show size-selective diffusive transport and effective separation of small molecules and salts from a model protein, with ≈2-100× increase in permeance along with selectivity better than or comparable to state-of-the-art commercially available polymeric dialysis membranes. The membranes constitute the largest fully functional NATMs fabricated via bottom-up nanopore formation, and can be easily scaled up to larger sizes permitted by CVD synthesis. The results highlight synergistic benefits in blending traditional membrane casting with bottom-up pore creation during graphene CVD for advancing NATMs toward practical applications.

In-field determination of soil ion content using a handheld device and screen-printed solid-state ion-selective electrodes.

Small-holding farmers in the developing world suffer from sub-optimal crop yields because they lack a soil diagnostic system that is affordable, usable, and actionable. This paper details the fabrication and characterization of an integrated point-of-use soil-testing system, comprised of disposable ion-selective electrode strips and a handheld electrochemical reader. Together, the strips and reader transduce soil ion concentrations into to an alphanumeric output that can be communicated via text message to a central service provider offering immediate, customized fertilizer advisory. The solid-state ion-selective electrode (SS-ISE) strips employ a two-electrode design with screen-printable carbon nanotube ink serving as the electrical contacts for the working and reference electrodes. The working electrode comprises a plasticizer-free butyl acrylate ion-selective membrane (ISM), doped with an ion-selective ionophore and lipophilic salt. Meanwhile, the reference electrode includes a screen-printed silver-silver chloride ink and a polyvinyl-butyral membrane, which is doped with sodium chloride for stable reference potentials. As a proof of concept, potassium-selective electrodes are studied, given potassium's essential role in plant growth and reproduction. The ISE-based system is reproducibly manufactured to yield a Nernstian response with a sub-micromolar detection limit (pK+ of 5.18 ± 0.08) and near-Nernstian sensitivity (61 mV/decade) in the presence of a 0.02 M strontium chloride extraction solution. Analysis of soil samples using the printed electrodes and reader yielded a correlation coefficient of 𝑅2 = 0.89 with respect to values measured via inductively coupled plasma atomic emission spectroscopy (ICP-AES). The reliable performance of this system is encouraging toward its deployment for soil nutrient management in resource-limited environments.

Antibody-modified conduits for highly selective cytokine elimination from blood.

Cytokines play an important role in dysregulated immune responses to infection, pancreatitis, ischemia/reperfusion injury, burns, hemorrhage, cardiopulmonary bypass, trauma, and many other diseases. Moreover, the imbalance between inflammatory and antiinflammatory cytokines can have deleterious effects. Here, we demonstrated highly selective blood-filtering devices - antibody-modified conduits (AMCs) - that selectively eliminate multiple specific deleterious cytokines in vitro. AMCs functionalized with antibodies against human vascular endothelial growth factor A or tumor necrosis factor α (TNF-α) selectively eliminated the target cytokines from human blood in vitro and maintained them in reduced states even in the face of ongoing infusion at supraphysiologic rates. We characterized the variables that determine AMC performance, using anti-human TNF-α AMCs to eliminate recombinant human TNF-α. Finally, we demonstrated selective cytokine elimination in vivo by filtering interleukin 1 ß from rats with lipopolysaccharide-induced hypercytokinemia.

A Scalable Route to Nanoporous Large-Area Atomically Thin Graphene Membranes by Roll-to-Roll Chemical Vapor Deposition and Polymer Support Casting.

Scalable, cost-effective synthesis and integration of graphene is imperative to realize large-area applications such as nanoporous atomically thin membranes (NATMs). Here, we report a scalable route to the production of NATMs via high-speed, continuous synthesis of large-area graphene by roll-to-roll chemical vapor deposition (CVD), combined with casting of a hierarchically porous polymer support. To begin, we designed and built a two zone roll-to-roll graphene CVD reactor, which sequentially exposes the moving foil substrate to annealing and growth atmospheres, with a sharp, isothermal transition between the zones. The configurational flexibility of the reactor design allows for a detailed evaluation of key parameters affecting graphene quality and trade-offs to be considered for high-rate roll-to-roll graphene manufacturing. With this system, we achieve synthesis of uniform high-quality monolayer graphene ( ID/ IG < 0.065) at speeds ≥5 cm/min. NATMs fabricated from the optimized graphene, via polymer casting and postprocessing, show size-selective molecular transport with performance comparable to that of membranes made from conventionally synthesized graphene. Therefore, this work establishes the feasibility of a scalable manufacturing process of NATMs, for applications including protein desalting and small-molecule separations.