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.

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.

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.

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.

Single-Layer Graphene Membranes Withstand Ultrahigh Applied Pressure.

High mechanical strength is essential for pressure-driven membrane separations with nanoporous single-layer graphene, but its ability to withstand high pressures remains to be demonstrated. We monitored failure of centimeter-scale single-layer graphene membranes on porous supports subjected to high pressures. Consistent with theory, the membranes were found to withstand higher pressures when placed on porous supports with smaller pore diameters, but failure occurred over a surprisingly broad range of pressures, attributed to heterogeneous susceptibility to failure at wrinkles, defects, and slack in the suspended graphene. Remarkably, nonwrinkled areas withstood pressure exceeding 100 bar at which many kinds of membrane suffer from compaction. Our study shows that single-layer graphene membranes can sustain ultrahigh pressure especially if the effect of wrinkles is isolated using supports with small pores and suggests the potential for the use of single-layer graphene in high-pressure membrane separations.

Knudsen effusion through polymer-coated three-layer porous graphene membranes.

Graphene membranes have the potential to exceed the permeance and selectivity limits of conventional gas separation membranes. Realizing this potential in practical systems relies on overcoming numerous scalability challenges, such as isolating or sealing permeable defects in macroscopic areas of graphene that can compromise performance and developing methods to create high densities of selective pores over large areas. This study focuses on a centimeter-scale membrane design, where leakage is reduced by substrate selection, permeable polymer film coating, and stacking of three independent layers of graphene, while (selective) pores are created by high density ion bombardment. The three-layer graphene provides high resistance to gas flow, which decreases with ion bombardment and results in selectivity consistent with Knudsen effusion. The results suggest that the permeable pores created in three layer graphene were larger than those required for molecular sieving and that designs based on single layer graphene may lend themselves more easily to molecular sieving of gases.

Enhanced water transport and salt rejection through hydrophobic zeolite pores.

The potential of improvements to reverse osmosis (RO) desalination by incorporating porous nanostructured materials such as zeolites into the selective layer in the membrane has spurred substantial research efforts over the past decade. However, because of the lack of methods to probe transport across these materials, it is still unclear which pore size or internal surface chemistry is optimal for maximizing permeability and salt rejection. We developed a platform to measure the transport of water and salt across a single layer of zeolite crystals, elucidating the effects of internal wettability on water and salt transport through the ≈5.5 Å pores of MFI zeolites. MFI zeolites with a more hydrophobic (i.e., less attractive) internal surface chemistry facilitated an approximately order of magnitude increase in water permeability compared to more hydrophilic MFI zeolites, while simultaneously fully rejecting both potassium and chlorine ions. However, our results also demonstrated approximately two orders of magnitude lower permeability compared to molecular simulations. This decreased performance suggests that additional transport resistances (such as surface barriers, pore collapse or blockages due to contamination) may be limiting the performance of experimental nanostructured membranes. Nevertheless, the inclusion of hydrophobic sub-nanometer pores into the active layer of RO membranes should improve both the water permeability and salt rejection of future RO membranes (Fasano et al 2016 Nat. Commun. 7 12762).

Nanofiltration across Defect-Sealed Nanoporous Monolayer Graphene.

Monolayer nanoporous graphene represents an ideal membrane for molecular separations, but its practical realization is impeded by leakage through defects in the ultrathin graphene. Here, we report a multiscale leakage-sealing process that exploits the nonpolar nature and impermeability of pristine graphene to selectively block defects, resulting in a centimeter-scale membrane that can separate two fluid reservoirs by an atomically thin layer of graphene. After introducing subnanometer pores in graphene, the membrane exhibited rejection of multivalent ions and small molecules and water flux consistent with prior molecular dynamics simulations. The results indicate the feasibility of constructing defect-tolerant monolayer graphene membranes for nanofiltration, desalination, and other separation processes.

Polymeric Nanoparticles Amenable to Simultaneous Installation of Exterior Targeting and Interior Therapeutic Proteins.

Effective delivery of therapeutic proteins is a formidable challenge. Herein, using a unique polymer family with a wide-ranging set of cationic and hydrophobic features, we developed a novel nanoparticle (NP) platform capable of installing protein ligands on the particle surface and simultaneously carrying therapeutic proteins inside by a self-assembly procedure. The loaded therapeutic proteins (e.g., insulin) within the NPs exhibited sustained and tunable release, while the surface-coated protein ligands (e.g., transferrin) were demonstrated to alter the NP cellular behaviors. In vivo results revealed that the transferrin-coated NPs can effectively be transported across the intestinal epithelium for oral insulin delivery, leading to a notable hypoglycemic response.

Evaporation-induced cavitation in nanofluidic channels.

Cavitation, known as the formation of vapor bubbles when liquids are under tension, is of great interest both in condensed matter science as well as in diverse applications such as botany, hydraulic engineering, and medicine. Although widely studied in bulk and microscale-confined liquids, cavitation in the nanoscale is generally believed to be energetically unfavorable and has never been experimentally demonstrated. Here we report evaporation-induced cavitation in water-filled hydrophilic nanochannels under enormous negative pressures up to -7 MPa. As opposed to receding menisci observed in microchannel evaporation, the menisci in nanochannels are pinned at the entrance while vapor bubbles form and expand inside. Evaporation in the channels is found to be aided by advective liquid transport, which leads to an evaporation rate that is an order of magnitude higher than that governed by Fickian vapor diffusion in macro- and microscale evaporation. The vapor bubbles also exhibit unusual motion as well as translational stability and symmetry, which occur because of a balance between two competing mass fluxes driven by thermocapillarity and evaporation. Our studies expand our understanding of cavitation and provide new insights for phase-change phenomena at the nanoscale.

Microstructured barbs on the North American porcupine quill enable easy tissue penetration and difficult removal.

North American porcupines are well known for their specialized hairs, or quills that feature microscopic backward-facing deployable barbs that are used in self-defense. Herein we show that the natural quill's geometry enables easy penetration and high tissue adhesion where the barbs specifically contribute to adhesion and unexpectedly, dramatically reduce the force required to penetrate tissue. Reduced penetration force is achieved by topography that appears to create stress concentrations along regions of the quill where the cross sectional diameter grows rapidly, facilitating cutting of the tissue. Barbs located near the first geometrical transition zone exhibit the most substantial impact on minimizing the force required for penetration. Barbs at the tip of the quill independently exhibit the greatest impact on tissue adhesion force and the cooperation between barbs in the 0-2 mm and 2-4 mm regions appears critical to enhance tissue adhesion force. The dual functions of barbs were reproduced with replica molded synthetic polyurethane quills. These findings should serve as the basis for the development of bio-inspired devices such as tissue adhesives or needles, trocars, and vascular tunnelers where minimizing the penetration force is important to prevent collateral damage.

Bioinspired multivalent DNA network for capture and release of cells.

Capture and isolation of flowing cells and particulates from body fluids has enormous implications in diagnosis, monitoring, and drug testing, yet monovalent adhesion molecules used for this purpose result in inefficient cell capture and difficulty in retrieving the captured cells. Inspired by marine creatures that present long tentacles containing multiple adhesive domains to effectively capture flowing food particulates, we developed a platform approach to capture and isolate cells using a 3D DNA network comprising repeating adhesive aptamer domains that extend over tens of micrometers into the solution. The DNA network was synthesized from a microfluidic surface by rolling circle amplification where critical parameters, including DNA graft density, length, and sequence, could readily be tailored. Using an aptamer that binds to protein tyrosine kinase-7 (PTK7) that is overexpressed on many human cancer cells, we demonstrate that the 3D DNA network significantly enhances the capture efficiency of lymphoblast CCRF-CEM cells over monovalent aptamers and antibodies, yet maintains a high purity of the captured cells. When incorporated in a herringbone microfluidic device, the 3D DNA network not only possessed significantly higher capture efficiency than monovalent aptamers and antibodies, but also outperformed previously reported cell-capture microfluidic devices at high flow rates. This work suggests that 3D DNA networks may have broad implications for detection and isolation of cells and other bioparticles.

Selective ionic transport through tunable subnanometer pores in single-layer graphene membranes.

We report selective ionic transport through controlled, high-density, subnanometer diameter pores in macroscopic single-layer graphene membranes. Isolated, reactive defects were first introduced into the graphene lattice through ion bombardment and subsequently enlarged by oxidative etching into permeable pores with diameters of 0.40 ± 0.24 nm and densities exceeding 10(12) cm(-2), while retaining structural integrity of the graphene. Transport measurements across ion-irradiated graphene membranes subjected to in situ etching revealed that the created pores were cation-selective at short oxidation times, consistent with electrostatic repulsion from negatively charged functional groups terminating the pore edges. At longer oxidation times, the pores allowed transport of salt but prevented the transport of a larger organic molecule, indicative of steric size exclusion. The ability to tune the selectivity of graphene through controlled generation of subnanometer pores addresses a significant challenge in the development of advanced nanoporous graphene membranes for nanofiltration, desalination, gas separation, and other applications.

Mechanisms of molecular permeation through nanoporous graphene membranes.

We present an investigation of molecular permeation of gases through nanoporous graphene membranes via molecular dynamics simulations; four different gases are investigated, namely helium, hydrogen, nitrogen, and methane. We show that in addition to the direct (gas-kinetic) flux of molecules crossing from the bulk phase on one side of the graphene to the bulk phase on the other side, for gases that adsorb onto the graphene, significant contribution to the flux across the membrane comes from a surface mechanism by which molecules cross after being adsorbed onto the graphene surface. Our results quantify the relative contribution of the bulk and surface mechanisms and show that the direct flux can be described reasonably accurately using kinetic theory, provided the latter is appropriately modified assuming steric molecule-pore interactions, with gas molecules behaving as hard spheres of known kinetic diameters. The surface flux is negligible for gases that do not adsorb onto graphene (e.g., He and H2), while for gases that adsorb (e.g., CH4 and N2) it can be on the order of the direct flux or larger. Our results identify a nanopore geometry that is permeable to hydrogen and helium, is significantly less permeable to nitrogen, and is essentially impermeable to methane, thus validating previous suggestions that nanoporous graphene membranes can be used for gas separation. We also show that molecular permeation is strongly affected by pore functionalization; this observation may be sufficient to explain the large discrepancy between simulated and experimentally measured transport rates through nanoporous graphene membranes.

Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D flow focusing towards in vivo study.

Microfluidic synthesis of nanoparticles (NPs) can enhance the controllability and reproducibility in physicochemical properties of NPs compared to bulk synthesis methods. However, applications of microfluidic synthesis are typically limited to in vitro studies due to low production rates. Herein, we report the parallelization of NP synthesis by 3D hydrodynamic flow focusing (HFF) using a multilayer microfluidic system to enhance the production rate without losing the advantages of reproducibility, controllability, and robustness. Using parallel 3D HFF, polymeric poly(lactide-co-glycolide)-b-polyethyleneglycol (PLGA-PEG) NPs with sizes tunable in the range of 13-150 nm could be synthesized reproducibly with high production rate. As a proof of concept, we used this system to perform in vivo pharmacokinetic and biodistribution study of small (20 nm diameter) PLGA-PEG NPs that are otherwise difficult to synthesize. Microfluidic parallelization thus enables synthesis of NPs with tunable properties with production rates suitable for both in vitro and in vivo studies. FROM THE CLINICAL EDITOR: Applications of nanoparticle synthesis with microfluidic methods are typically limited to in vitro studies due to low production rates. The team of authors of this proof-of-principle study reports on the successful parallelization of NP synthesis by 3D hydrodynamic flow focusing using a multilayer microfluidic system to enhance production rate without losing the advantages of reproducibility, controllability, and robustness.

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.

Integration of solid-state nanopores in microfluidic networks via transfer printing of suspended membranes.

Solid-state nanopores have emerged as versatile single-molecule sensors for applications including DNA sequencing, protein unfolding, micro-RNA detection, label-free detection of single nucleotide polymorphisms, and mapping of DNA-binding proteins involved in homologous recombination. While machining nanopores in dielectric membranes provides nanometer-scale precision, the rigid silicon support for the membrane contributes capacitive noise and limits integration with microfluidic networks for sample preprocessing. Herein, we demonstrate a technique to directly transfer solid-state nanopores machined in dielectric membranes from a silicon support into a microfluidic network. The resulting microfluidic-addressable nanopores can sense single DNA molecules at high bandwidths and with low noise, owing to significant reductions in membrane capacitance. This strategy will enable large-scale integration of solid-state nanopores with microfluidic upstream and downstream processing and permit new functions with nanopores such as complex manipulations for multidimensional analysis and parallel sensing in two and three-dimensional architectures.

Self-sorting of deformable particles in an asynchronous logic microfluidic circuit.

A microfluidic circuit can automatically sort deformable particles based on the hydrodynamic resistance that the particles induce in a constrained microfluidic channel while flowing through it.

Spontaneous formation of heterogeneous patches on polymer-lipid core-shell particle surfaces during self-assembly.

Spontaneous formation of heterogeneous patches on the surface of lipid-based nanoparticles (NPs) and microparticles (MPs) due to the segregation of two different functional groups. Patch formation is observed when tracing the functional groups with quantum dots, gold nanoparticles, and fluorescent dyes. This discovery could have important implications for the future design of self-assembled NPs and MPs for different biomedical applications.