Smart Microcapsules with Molecular Polarity‐ and Temperature‐Dependent Permeability

Microcapsules with molecule‐selective permeation are appealing as microreactors, capsule‐type sensors, drug and cell carriers, and artificial cells. To accomplish molecular size‐ and charge‐selective permeation, regular size of pores and surface charges have been formed in the membranes. However, it remains an important challenge to provide advanced regulation of transmembrane transport. Here, smart microcapsules are designed that provide molecular polarity‐ and temperature‐dependent permeability. With capillary microfluidic devices, water‐in‐oil‐in‐water (W/O/W) double‐emulsion drops are prepared, which serve as templates to produce microcapsules. The oil shell is composed of two monomers and dodecanol, which turns to a polymeric framework whose continuous voids are filled with dodecanol upon photopolymerization. One of the monomers provides mechanical stability of the framework, whereas the other serves as a compatibilizer between growing polymer and dodecanol, preventing macrophase separation. Above melting point of dodecanol, molecules that are soluble in the molten dodecanol are selectively allowed to diffuse across the shell, where the rate of transmembrane transport is strongly influenced by partition coefficient. The rate is drastically lowered for temperatures below the melting point. This molecular polarity‐ and temperature‐dependent permeability renders the microcapsules potentially useful as drug carriers for triggered release and contamination‐free microreactors and microsensors.     

Smart Drug Delivery Nanocarriers with Self‐Assembled DNA Nanostructures

Self‐assembled DNA nanostructures have emerged as a type of nano‐biomaterials with precise structures, versatile functions and numerous applications. One particularly promising application of these DNA nanostructures is to develop universal nanocarriers for smart and targeted drug delivery. DNA is the genetic material in nature, and inherently biocompatible. Nevertheless, cell membranes are barely permeable to naked DNA molecules, either single‐ or double‐ stranded; transport across the cell membrane is only possible with the assistance of transfection agents. Interestingly, recent studies revealed that many DNA nanostructures could readily go into cells with high cell uptake efficiency. In this Progress Report, we will review recent advances on using various DNA nanostructures, e.g., DNA nanotubes, DNA tetrahedra, and DNA origami nanorobot, as drug delivery nanocarriers, and demonstrate several examples aiming at therapeutic applications with CpG‐based immunostimulatory and siRNA‐based gene silencing oligonucleotides.     

Permeability of the nuclear envelope at isolated Xenopus oocyte nuclei studied by scanning electrochemical microscopy

In interphase eukaryotic cells, molecular transport between the cytoplasm and the nucleus is mediated by the nuclear pore complex (NPC), which perforates the double-membraned nuclear envelope (NE). Local permeability of the NE at large intact nuclei (approximately 400 microm in diameter) isolated from Xenopus laevis oocytes was studied by scanning electrochemical microscopy (SECM). Steady-state tip current versus tip-nucleus distance curves (approach curves) were measured with 10- and 2-microm-diameter Pt disk microelectrodes at the nuclei in isotonic buffer solutions containing redox-active molecules. The approach curves in the normalized form are independent of the tip diameter, indicating diffusion-limited membrane transport of the redox molecules. SECM chronoamperometry demonstrated that a decrease in the steady-state tip current at short tip-nucleus distances is due to smaller diffusion coefficients and concentrations of the redox molecules in the nucleus than those in the buffer solution. The experimental approach curves fit very well with theoretical ones for freely permeable membranes, yielding the NE permeability to the molecules that is at least 2 orders of magnitude larger than permeability of bilayer lipid membranes and cell membranes. This result indicates that passive transport of the redox molecules across the NE is facilitated by open NPC pores. The flux of the redox molecules sustainable by a single NPC channel (>9.8 x 10(6) molecules per NPC per second) and the diameter of the channel pore (>15 nm) were estimated from the SECM data by assuming the NE as an array of nanometer-sized NPC pores. The effects of the redox molecules on the nucleus and the NPC function were examined by studying signal-mediated nuclear import of rhodamine-labeled bovine serum albumin with and without nuclear localization signals by fluorescence microscopy.     

Graphynes for Water Desalination and Gas Separation

Selective transport of mass through membranes, so‐called separation, is fundamental to many industrial applications, e.g., water desalination and gas separation. Graphynes, graphene analogs yet containing intrinsic uniformly distributed pores, are excellent candidates for highly permeable and selective membranes owing to their extreme thinness and high porosity. Graphynes exhibit computationally determined separation performance far beyond experimentally measured values of commercial state‐of‐the‐art polyamide membranes; they also offer advantages over other atomically thin membranes like porous graphene in terms of controllability in pore geometry. Here, recent progress in proof‐of‐concept computational research into various graphynes for water desalination and gas separation is discussed, and their theoretically predicted outstanding permeability and selectivity are highlighted. Challenges associated with the future development of graphyne‐based membranes are further analyzed, concentrating on controlled synthesis of graphyne, maintenance of high structural stability to withstand loading pressures, as well asthe demand for accurate computational characterization of separation performance. Finally, possible directions are discussed to align future efforts in order to push graphynes and other 2D material membranes toward practical separation applications.     

Creation of Nonspherical Microparticles through Osmosis‐Driven Arrested Coalescence of Microfluidic Emulsions

Droplet‐based microfluidics enable the production of emulsions and microparticles with spherical shapes, but the high‐throughput fabrication of nonspherical emulsions and microparticles still remains challenging because interfacial tension plays a dominant role during preparation. Herein, ionic liquids (ILs) containing salts, which possess sufficient osmotic pressure to realize water transport and phase separation, are introduced as inner cores of oil‐in‐oil‐in‐water double emulsions and it is shown that nonspherical emulsions can be constructed by osmosis‐driven arrested coalescence of inner cores. Subsequently, ultraviolet polymerization of the nonspherical emulsions leads to nonspherical microparticles. By tailoring the number, composition, and size of inner cores as well as coalescence time, a variety of nonspherical shapes such as dumbbell, rod, spindle, snowman, tumbler, three‐pointed star, triangle, and scalene triangle are created. Importantly, benefitting from excellent solvency of ILs, this system can serve as a general platform to produce nonspherical microparticles made from different materials. Moreover, by controlling the osmotic pressure, programmed coalescence of inner cores in double emulsions is realizable, which indicates the potential to build microreactors. Thus, a simple and high‐throughput strategy to create nonspherical microparticles with arrested coalescence shapes is developed for the first time and can be further used to construct novel materials and microreactors.     

Selective Nanoscale Mass Transport across Atomically Thin Single Crystalline Graphene Membranes

Atomically thin single crystals, without grain boundaries and associated defect clusters, represent ideal systems to study and understand intrinsic defects in materials, but probing them collectively over large area remains nontrivial. In this study, the authors probe nanoscale mass transport across large‐area (≈0.2 cm²) single‐crystalline graphene membranes. A novel, polymer‐free picture frame assisted technique, coupled with a stress‐inducing nickel layer is used to transfer single crystalline graphene grown on silicon carbide substrates to flexible polycarbonate track etched supports with well‐defined cylindrical ≈200 nm pores. Diffusion‐driven flow shows selective transport of ≈0.66 nm hydrated K⁺ and Cl^? ions over ≈1 nm sized small molecules, indicating the presence of selective sub‐nanometer to nanometer sized defects. This work presents a framework to test the barrier properties and intrinsic quality of atomically thin materials at the sub‐nanometer to nanometer scale over technologically relevant large areas, and suggests the potential use of intrinsic defects in atomically thin materials for molecular separations or desalting.     

Microstructural and Interfacial Designs of Oxygen‐Permeable Membranes for Oxygen Separation and Reaction–Separation Coupling

Mixed ionic–electronic conducting oxygen‐permeable membranes can rapidly separate oxygen from air with 100% selectivity and low energy consumption. Combining reaction and separation in an oxygen‐permeable membrane reactor significantly simplifies the technological scheme and reduces the process energy consumption. Recently, materials design and mechanism investigations have provided insight into the microstructural and interfacial effects. The microstructures of the membrane surfaces and bulk are closely related to the interfacial oxygen exchange kinetics and bulk diffusion kinetics. Therefore, the permeability and stability of oxygen‐permeable membranes with a single‐phase structure and a dual‐phase structure can be adjusted through their microstructural and interfacial designs. Here, recent advances in the development of oxygen permeation models that provide a deep understanding of the microstructural and interfacial effects, and strategies to simultaneously improve the permeability and stability through microstructural and interfacial design are discussed in detail. Then, based on the developed high‐performance membranes, highly effective membrane reactors for process intensification and new technology developments are highlighted. The new membrane reactors will trigger innovations in natural gas conversion, ammonia synthesis, and hydrogen‐related clean energy technologies. Future opportunities and challenges in the development of oxygen‐permeable membranes for oxygen separation and reaction–separation coupling are also explored.     

Optically Controlled Pore Formation in Self‐Sealing Giant Porphyrin Vesicles

Efforts to develop self‐contained microreactors and artificial cells have been limited by difficulty in generating membranes that can be robustly and repeatedly manipulated to load and release cargo from phospholipid compartments. Here we describe a purely optical method to form pores in a membrane generated from porphyrin‐phospholipid conjugates electro‐assembled into microscale giant porphyrin vesicles and manipulated using confocal microscopy. The pores in the membrane resealed within a minute allowing for repeated pore formation with precise spatial and temporal control and optical gating to allow selective diffusion of biomolecules across the membrane. Temporal control of pore formation was illustrated by performing sequential DNA hybridization reactions. A biotin‐avidin based strategy was developed to selectively attach enzymes to the interior of the vesicle, demonstrating spatial control and the potential of giant porphyrin vesicles as versatile microreactors.     

Fatty Acid/Phospholipid Blended Membranes: A Potential Intermediate State in Protocellular Evolution

Prior to the evolution of membrane proteins, intrinsic membrane stability and permeability to polar solutes are essential features of a primitive cell membrane. These features are difficult to achieve simultaneously in model protocells made of either pure fatty acid or phospholipid membranes, raising the intriguing question of how the transition from fatty acid to phospholipid membranes might have occurred while continuously supporting encapsulated reactions required for genomic replication. Here, the properties of a blended membrane system composed of both oleic acid (OA), a monoacyl fatty acid, and 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine (POPC), a diacyl phospholipid are described. This hybrid vesicle system exhibits high stability to divalent cations (Mg²⁺), while simultaneously maintaining its permeability to small charged molecules such as nucleotides and divalent ions such as Mg²⁺. This combination of features facilitates key reactions expected to occur during a transition from primitive to modern cells, including nonenzymatic RNA replication, and is also compatible with highly evolved functions such as the ribosomal translation of a protein. The observations support the hypothesis that the early transition from fatty acid to phospholipid membranes could be accomplished through intermediate states in which membranes are composed of amphiphile mixtures, and do not require protein transporters.     

Forming Sticky Droplets from Slippery Polymer Zwitterions

Polymer zwitterions are generally regarded as hydrophilic and repellant or “slippery” materials. Here, a case is described in which the polymer zwitterion structure is tailored to decrease water solubility, stabilize emulsion droplets, and promote interdroplet adhesion. Harnessing the upper critical solution temperature of sulfonium‐ and ammonium‐based polymer zwitterions in water, adhesive droplets are prepared by adding organic solvent to an aqueous polymer solution at elevated temperature, followed by agitation to induce emulsification. Droplet aggregation is observed as the mixture cools. Variation of salt concentration, temperature, polymer concentration, and polymer structure modulates these interdroplet interactions, resulting in distinct changes in emulsion stability and fluidity. Under attractive conditions, emulsions encapsulating 50–75% oil undergo gelation. By contrast, emulsions prepared under conditions where droplets are nonadhesive remain fluid and, for oil fractions exceeding 0.6, coalescence is observed. The uniquely reactive nature of the selected zwitterions allows their in situ modification and affords a route to chemically trigger deaggregation and droplet dispersion. Finally, experiments performed in a microfluidic device, in which droplets are formed under conditions that either promote or suppress adhesion, confirm the salt‐responsive character of these emulsions and the persistence of adhesive interdroplet interactions under flow.     

Osmocapsules for Direct Measurement of Osmotic Strength

Monodisperse microcapsules with ultra‐thin membranes are microfluidically designed to be highly sensitive to osmotic pressure, thereby providing a tool for the direct measurement of the osmotic strength. To make such osmocapsules, water‐in‐oil‐in‐water double‐emulsion drops with ultra‐thin shells are prepared as templates through emulsification of core–sheath biphasic flow in a capillary microfluidic device. When photocurable monomers are used as the oil phase, the osmocapsules are prepared by in‐situ photopolymerization of the monomers, resulting in semipermeable membranes with a relatively large ratio of membrane thickness to capsule radius, approximately 0.02. These osmocapsules are buckled by the outward flux of water when they are subjected to a positive osmotic pressure difference above 125 kPa. By contrast, evaporation‐induced consolidation of middle‐phase containing polymers enables the production of osmocapsules with a small ratio of membrane thickness to capsule radius of approximately 0.002. Such an ultra‐thin membrane with semi‐permeability makes the osmocapsules highly sensitive to osmotic pressure; a positive pressure as small as 12.5 kPa induces buckling of the capsules. By employing a set of distinct osmocapsules confining aqueous solutions with different osmotic strengths, the osmotic strength of unknown solutions can be estimated through observation of the capsules that are selectively buckled. This approach provides the efficient measurement of the osmotic strength using only a very small volume of liquid, thereby providing a useful alternative to other measurement methods which use complex setups. In addition, in‐vivo measurement of the osmotic strength can be potentially accomplished by implanting these biocompatible osmocapsules into tissue, which is difficult to achieve using conventional methods.     

Lipid Bilayers on a Picoliter Microdroplet Array for Rapid Fluorescence Detection of Membrane Transport

This paper describes picoliter‐sized lipid bilayer chambers and their theoretical model for the rapid detection of membrane transport. To prepare the chambers, semispherical aqueous droplets are patterned on a hydrophilic/hydrophobic substrate and then brought into contact with another aqueous droplet in lipid‐dispersed organic solvent, resulting in the formation of the lipid bilayers on the semispherical droplets. The proposed method implements the lipid bilayer chambers with 25‐fold higher ratio of lipid membrane area (S) to chamber volume (V) compared to the previous spherical droplet chambers. Using these chambers, we are able to trace the time‐course of Ca²⁺ influx through α‐hemolysin pores by a fluorescent indicator. Moreover, we confirm that the detection time of the substrate transport is inversely proportional to the S/V ratio of the developed chambers, which is consistent with the simulation results based on the developed model. Our chambers and model might be useful for rapid functional analyses of membrane transport phenomena.     

Ultrathin Dual‐Scale Nano‐ and Microporous Membranes for Vascular Transmigration Models

Selective cellular transmigration across the microvascular endothelium regulates innate and adaptive immune responses, stem cell localization, and cancer cell metastasis. Integration of traditional microporous membranes into microfluidic vascular models permits the rapid assay of transmigration events but suffers from poor reproduction of the cell permeable basement membrane. Current microporous membranes in these systems have large nonporous regions between micropores that inhibit cell communication and nutrient exchange on the basolateral surface reducing their physiological relevance. Here, the use of 100 nm thick continuously nanoporous silicon nitride membranes as a base substrate for lithographic fabrication of 3 µm pores is presented, resulting in a highly porous (≈30%), dual‐scale nano‐ and microporous membrane for use in an improved vascular transmigration model. Ultrathin membranes are patterned using a precision laser writer for cost‐effective, rapid micropore design iterations. The optically transparent dual‐scale membranes enable complete observation of leukocyte egress across a variety of pore densities. A maximal density of ≈14 micropores per cell is discovered beyond which cell–substrate interactions are compromised giving rise to endothelial cell losses under flow. Addition of a subluminal extracellular matrix rescues cell adhesion, allowing for the creation of shear‐primed endothelial barrier models on nearly 30% continuously porous substrates.     

Graphitic Carbon Nitride Stabilizers Meet Microfluidics: From Stable Emulsions to Photoinduced Synthesis of Hollow Polymer Spheres

Graphitic carbon nitride (g‐CN) has been utilized as a heterogeneous catalyst, but is usually not very well dispersible. The amphiphilic character of g‐CN can be altered by surface modifications of g‐CN nanopowders. Introducing hydrophilicity or hydrophobicity is a promising avenue for producing advanced emulsion systems. In this study, a special surface‐modified g‐CN is used to form stable Pickering emulsions. Using a PDMS‐based microfluidic device designed for stable production of both single and double emulsions, it is shown that surface‐modified g‐CNs allow the manufacture of unconventionally stable and precise Pickering emulsions. Shell thickness of the double emulsions is varied to emphasize the robustness of the device and also to demonstrate the extraordinary stabilization brought by the surface‐modified carbon nitride used in this study. Due to the electrostatic stabilization also in the oil phase, double emulsions are centered. Finally, when produced from polymerizable styrene, hollow polymer microparticles are formed with precise and tunable sizes, where g‐CN is utilized as the only stabilizer and photoinitiator.     

Ultraselective Carbon Molecular Sieve Membranes with Tailored Synergistic Sorption Selective Properties

Membrane‐based separations can reduce the energy consumption and the CO₂ footprint of large‐scale fluid separations, which are traditionally practiced by energy‐intensive thermally driven processes. Here, a new type of membrane structure based on nanoporous carbon is reported, which, according to this study, is best referred to as carbon/carbon mixed‐matrix (CCMM) membranes. The CCMM membranes are formed by high‐temperature (up to 900 °C) pyrolysis of polyimide precursor hollow‐fiber membranes. Unprecedentedly high permselectivities are seen in CCMM membranes for CO₂/CH₄, N₂/CH₄, He/CH₄, and H₂/CH₄ separations. Analysis of permeation data suggests that the ultrahigh selectivities result from substantially increased sorption selectivities, which is hypothetically owing to the formation of ultraselective micropores that selectively exclude the bulkier CH₄ molecules. With tunable sorption selectivities, the CCMM membranes outperform flexible polymer membranes and traditional rigid molecular‐sieve membranes. The capability to increase sorption selectivities is a powerful tool to leverage diffusion selectivities, and has opened the door to many challenging and economically important fluid separations that require ultrafine differentiation of closely sized molecules.     

Boron Nitride Nanotubes Selectively Permeable to Cations or Anions

Biological ion channels in membranes are selectively permeable to specific ionic species. They maintain the resting membrane potential, generate propagated action potentials, and control a wide variety of cell functions. Here it is demonstrated theoretically that boron nitride nanotubes have the ability to carry out some of the important functions of biological ion channels. Boron nitride nanotubes with radii of 4.83 and 5.52 Å embedded in a silicon nitride membrane are selectively permeable to cations and anions, respectively. They broadly mimic some of the permeation characteristics of gramicidin and chloride channels. Using distributional molecular dynamics, which is a combination of molecular and stochastic dynamics simulations, the properties of these engineered nanotubes are characterized, such as the free energy encountered by charged particles, the water‐ion structure within the pore, and the current–voltage and current–concentration profiles. These engineered nanotubes have potential applications as sensitive biosensors, antibiotics, or filtration devices.     

Constructing Connected Paths between UiO‐66 and PIM‐1 to Improve Membrane CO2 Separation with Crystal‐Like Gas Selectivity

Most metal–organic‐framework‐ (MOF‐) based hybrid membranes face the challenge of low gas permeability in CO₂ separation. This study presents a new strategy of interweaving UiO‐66 and PIM‐1 to build freeways in UiO‐66‐CN@sPIM‐1 membranes for fast CO₂ transport. In this strategy, sPIM‐1 is rigidified via thermal treatment to make polymer voids permanent, and concurrently polymer chains are mutually linked onto UiO‐66‐CN crystals to minimize interfacial defects. The pore chemistry of UiO‐66‐CN is kept intact in hybrid membranes, allowing full utilization of MOF pores and selective adsorption for CO₂. Separation results show that UiO‐66‐CN@sPIM‐1 membranes possess exceptionally high CO₂ permeability (15433.4–22665 Barrer), approaching to that of UiO‐66‐NH₂ crystal (65–75% of crystal‐derived permeability). Additionally, the CO₂/N₂ permeation selectivity for a representative membrane (23.9–28.6) moves toward that of single crystal (24.6–29.6). The unique structure and superior CO₂/N₂ separation performance make UiO‐66‐CN@sPIM‐1 membranes promising in practical CO₂ separations.     

Self‐Assembly of Thiourea‐Crosslinked Graphene Oxide Framework Membranes toward Separation of Small Molecules

The poor mechanical strength of graphene oxide (GO) membranes, caused by the weak interlamellar interactions, poses a critical challenge for any practical application. In addition, intrinsic but large‐sized 2D channels of stacked GO membranes lead to low selectivity for small molecules. To address the mechanical strength and 2D channel size control, thiourea covalent‐linked graphene oxide framework (TU‐GOF) membranes on porous ceramics are developed through a facile hydrothermal self‐assembly synthesis. With this strategy, thiourea‐bridged GO laminates periodically through the dehydration condensation reactions via ? NH₂ and/or ? SH with ? O?C? OH as well as the nucleophilic addition reactions of ? NH₂ to C? O? C, leading to narrowed and structurally well‐defined 2D channels due to the small dimension of the covalent TU‐link and the deoxygenated processes. The resultant TU‐GOF/ceramic composite membranes feature excellent sieving capabilities for small species, leading to high hydrogen permselectivities and nearly complete rejections for methanol and small ions in gas, solvent, and saline water separations. Moreover, the covalent bonding formed at the GO/support and GO/GO interfaces endows the composite membrane with significantly enhanced stability.     

Unraveling the Water Impermeability Discrepancy in CVD‐Grown Graphene

Graphene has recently attracted particular interest as a flexible barrier film preventing permeation of gases and moistures. However, it has been proved to be exceptionally challenging to develop large‐scale graphene films with little oxygen and moisture permeation suitable for industrial uses, mainly due to the presence of nanometer‐sized defects of obscure origins. Here, the origins of water permeable routes on graphene‐coated Cu foils are investigated by observing the micrometer‐sized rusts in the underlying Cu substrates, and a site‐selective passivation method of the nanometer‐sized routes is devised. It is revealed that nanometer‐sized holes or cracks are primarily concentrated on graphene wrinkles rather than on other structural imperfections, resulting in severe degradation of its water impermeability. They are found to be predominantly induced by the delamination of graphene bound to Cu as a release of thermal stress during the cooling stage after graphene growth, especially at the intersection of the Cu step edges and wrinkles owing to their higher adhesion energy. Furthermore, the investigated routes are site‐selectively passivated by an electron‐beam‐induced amorphous carbon layer, thus a substantial improvement in water impermeability is achieved. This approach is likely to be extended for offering novel barrier properties in flexible films based on graphene and on other atomic crystals.