Highly Efficient Gating of Electrically Actuated Nanochannels for Pulsatile Drug Delivery Stemming from a Reversible Wettability Switch

Many ion channels in the cell membrane are believed to function as gates that control the water and ion flow through the transitions between an inherent hydrophobic state and a stimuli‐induced hydration state. The construction of nanofluidic gating systems with high gating efficiency and reversibility is inspired by this hydrophobic gating behavior. A kind of electrically actuated nanochannel is developed by integrating a polypyrrole (PPy) micro/nanoporous film doped with perfluorooctanesulfonate ions onto an anodic aluminum oxide nanoporous membrane. Stemming from the reversible wettability switch of the doped PPy film in response to the applied redox potentials, the nanochannels exhibit highly efficient and reversible gating behaviors. The optimized gating ratio is over 10⁵, which is an ultrahigh value when compared with that of the existing reversibly gated nanochannels with comparable pore diameters. Furthermore, the gating behavior of the electrically actuated nanochannels shows excellent repeatability and stability. Based on this highly efficient and reversible gating function, the electrically actuated nanochannels are further applied for drug delivery, which achieves the pulsatile release of two water‐soluble drug models. The electrically actuated nanochannels may find potential applications in accurate and on‐demand drug therapy.     

Non-equilibrium all-atom molecular dynamics simulations of free and tethered DNA molecules in nanochannel shear flows

In order to gain insight into the mechanical and dynamical behaviour of free and tethered short chains of ss/ds DNA molecules in flow, and in parallel to investigate the properties of long chain molecules in flow fields, we have developed a series of quantum and molecular methods to extend the well developed equilibrium software CHARMM to handle non-equilibrium dynamics. These methods have been applied to cases of DNA molecules in shear flows in nanochannels. Biomolecules, both free and wall-tethered, have been simulated in the all-atom style in solvent-filled nanochannels. The new methods were demonstrated by carrying out NEMD simulations of free single-stranded DNA (ssDNA) molecules of 21 bases as well as double-stranded DNA (dsDNA) molecules of 21 base pairs tethered on gold surfaces in an ionic water shear flow. The tethering of the linker molecule (6-mercapto-1-hexanol) to perfect Au(111) surfaces was parametrized based on density functional theory (DFT) calculations. Force field parameters were incorporated into the CHARMM database. Gold surfaces are simulated in a Lennard-Jones style model that was fitted to the Morse potential model of bulk gold. The bonding force of attachment of the DNA molecules to the gold substrate linker molecule was computed to be up to a few nN when the DNA molecules are fully stretched at high shear rates. For the first time, we calculated the relaxation time of DNA molecules in picoseconds (ps) and the hydrodynamic force up to a few nanoNewtons (nN) per base pair in a nanochannel flow. The velocity profiles in the solvent due to the presence of the tethered DNA molecules were found to be nonlinear only at high shear flow rates. Free ssDNA molecules in a shear flow were observed to behave differently from each other depending upon their initial orientation in the flow field. Both free and tethered DNA molecules are clearly observed to be stretching, rotating and relaxing. Methods developed in this initial work can be incorporated into multiscale simulations including quantum mechanical, molecular and the microfluidic continuum regimes. The results may also be useful in extending existing macroscopic empirical models of DNA response dynamics in shear flows.     

Tuneable elastomeric nanochannels for nanofluidic manipulation

Fluidic transport through nanochannels offers new opportunities to probe fundamental nanoscale transport phenomena and to develop tools for manipulating DNA, proteins, small molecules and nanoparticles. The small size of nanofabricated devices and the accompanying increase in the effect of surface forces, however, pose challenges in designing and fabricating flexible nanofluidic systems that can dynamically adjust their transport characteristics according to the handling needs of various molecules and nanoparticles. Here, we describe the use of nanoscale fracturing of oxidized poly(dimethylsiloxane) to conveniently fabricate nanofluidic systems with arrays of nanochannels that can actively manipulate nanofluidic transport through dynamic modulation of the channel cross-section. We present the design parameters for engineering material properties and channel geometry to achieve reversible nanochannel deformation using remarkably small forces. We demonstrate the versatility of the elastomeric nanochannels through tuneable sieving and trapping of nanoparticles, dynamic manipulation of the conformation of single DNA molecules and in situ photofabrication of movable polymeric nanostructures.     

A Novel Biosensor Based on Molybdenum Disulfide (MoS2) Modified Porous Anodic Aluminum Oxide Nanochannels for Ultrasensitive microRNA‐155 Detection

Artificial photoresponsive nanochannels have attracted widespread attention because of their capacity to achieve ion transport through light modulation. Herein, a biosensor for ultrasensitive miRNA‐155 detection is devised based on molybdenum disulfide (MoS₂) modified porous anodic aluminum oxide (AAO) photoresponsive nanochannels by atomic layer deposition (ALD). According to the optimized experimental results, when the cycles of ALD, the wavelength, and the power of the excitation laser are 70 cycles, 450 nm, and 80 mW, respectively, the most supreme photocurrent performance of these photoresponsive nanochannels are obtained. AAO nanochannels modified with MoS₂ can work as a photoelectrochemical (PEC) biosensor by generating photoexcitation current; what is more, the high channel density in AAO can magnify the ion current signal response effectively by aggrandizing the flux of electroactive species. By using AAO photoresponsive nanochannels with an average diameter of 150 nm as PEC biosensor, an ultrasensitive detection record ranging from 0.01 fM to 0.01 nM with a detection limit of 3 aM can be achieved. This work not only proposes a simple method for manufacturing semiconductor photoresponsive nanochannels, but also exhibits great potential in the ultrasensitive detection of biomolecules.     

Tunable Confinement for Bridging Single‐Cell Manipulation and Single‐Molecule DNA Linearization

DNA linearization by nanoconfinement has offered a new avenue toward large‐scale genome mapping. The ability to smoothly interface the widely different length scales from cell manipulation to DNA linearization is critical to the development of single‐cell genomic mapping or sequencing technologies. Conventional nanochannel technologies for DNA analysis suffer from complex fabrication procedures, DNA stacking at the nanochannel entrance, and inefficient solution exchange. In this work, a dynamic and tunable confinement strategy is developed to manipulate and linearize genomic‐length DNA molecules from a single cell. By leveraging pneumatic microvalve control and elastomeric collapse, an array of nanochannels with confining dimension down to 20 nm and length up to sub‐millimeter is created and can be dynamically tuned in size. The curved edges of the microvalve form gradual transitions from microscale to nanoscale confinement, smoothly facilitating DNA entry into the nanochannels. A unified micro/nanofluidic device that integrates single‐cell trapping and lysis, DNA extraction, purification, labeling, and linearization is developed based on dynamically controllable nanochannels. Mbp‐long DNA molecules are extracted directly from a single cell and in situ linearized in the nanochannels. The device provides a facile and promising platform to achieve the ultimate goal of single‐cell, single‐genome analysis.     

Electrokinetic transport in nanochannels. 2. Experiments

We present an experimental study of nanoscale electrokinetic transport in custom-fabricated quartz nanochannels using quantitative epifluorescence imaging and current monitoring techniques. One aim is to yield insight into electrical double layer physics and study the applicability of continuum theory to nanoscale electrokinetic systems. A second aim is to explore a new separation modality offered by nanoscale electrophoretic separations. We perform parametric variations of applied electric field, channel depth, background buffer concentration, and species valence to impose variations on zeta potential, effective mobility, and Debye length among other parameters. These measurements were used to validate a continuum theory-based analytical model presented in the first of this two-paper series. Our results confirm the usefulness of continuum theory in predicting electrokinetic transport and electrophoretic separations in nanochannels. Our model leverages independent measurements of zeta potential performed in a microchannel system at electrolyte concentrations of interest. These data yield a zeta potential versus concentration relation that is used as a boundary condition for the nanochannel electrokinetic transport model. The data and model comparisons together show that the effective mobility governing electrophoretic transport of charged species in nanochannels depends not only on ion mobility values but also on the shape of the electric double layer and analyte ion valence. We demonstrate a method we term electrokinetic separation by ion valence, whereby both ion valence and mobility may be determined independently from a comparison of micro- and nanoscale transport measurements.     

Contact and edge effects in graphene devices

Electrical transport studies on graphene have been focused mainly on the linear dispersion region around the Fermi level and, in particular, on the effects associated with the quasiparticles in graphene behaving as relativistic particles known as Dirac fermions. However, some theoretical work has suggested that several features of electron transport in graphene are better described by conventional semiconductor physics. Here we use scanning photocurrent microscopy to explore the impact of electrical contacts and sheet edges on charge transport through graphene devices. The photocurrent distribution reveals the presence of potential steps that act as transport barriers at the metal contacts. Modulations in the electrical potential within the graphene sheets are also observed. Moreover, we find that the transition from the p- to n-type regime induced by electrostatic gating does not occur homogeneously within the sheets. Instead, at low carrier densities we observe the formation of p-type conducting edges surrounding a central n-type channel.     

Fabrication of nanofluidic biochips with nanochannels for applications in DNA analysis

With the development of nanotechnology, great progress has been made in the fabrication of nanochannels. Nanofluidic biochips based on nanochannel structures allow biomolecule transport, bioseparation, and biodetection. The domain applications of nanofluidic biochips with nanochannels are DNA stretching and separation. In this Review, the general fabrication methods for nanochannel structures and their applications in DNA analysis are discussed. These representative fabrication approaches include conventional photolithography, interference lithography, electron-beam lithography, nanoimprint lithography and polymer nanochannels. Other nanofabrication methods used to fabricate unique nanochannels, including sub-10-nm nanochannels, single nanochannels, and vertical nanochannels, are also mentioned. These nanofabrication methods provide an effective way to form nanoscale channel structures for nanofluidics and biosensor devices for DNA separation, detection, and sensing. The broad applications of nanochannels and future perspectives are also discussed.     

A model of vacancy flux induced segregation to grain-boundaries during cooling

A recently developed method of analysis provided a direct measure of grain-boundary solute enrichment in slowly cooled Zn-Cd alloys as a function of holding temperature. These experimental data are here compared with the change of boundary solute enrichment computed from a model based on the vacancy flux generated uphill diffusion of solute to boundaries. The agreement between experiment and theory is satisfactory. This agreement is considered to be a direct proof that previously reported grain-boundary hardening of slowly cooled dilute alloys is a consequence of non-equilibrium solute adsorption.     

A Magnetic Gated Nanofluidic Based on the Integration of a Superhydrophilic Nanochannels and a Reconfigurable Ferrofluid

The design of intelligent gating in nanoscale is the subject of intense research motivated by a broad potential impact on science and technology. However, the existing designs require complex modification and are unstable, which restrict their practical applications. Here, a magnetic gated nanofluidic is reported based on the integration of superhydrophilic membranes and reconfigurable ferrofluid, which realizes the gating of the nanochannel by adjusting the steric configuration of the ferrofluid. This system could achieve ultrahigh gating ratio up to 10 000 and excellent stability up to 130 cycles without attenuation. Experiments and theoretical calculations demonstrate that the switch is controlled by the synergy of magnetic force and the interfacial tension. The introduction of ferrofluid and superhydrophilic nanochannels in this work presents an important paradigm for the nanofluidic systems and opens a new and promising avenue to various developments in the fields of materials science, which may be utilized in medical devices, nanoscale synthesis, and environmental analysis.     

Redox switch of ionic transport in conductive polypyrrole-engineered unipolar nanofluidic diodes

Controlling ion transport in nanoconfined spaces is a key task for the creation of smart nanofluidic devices.In this work,redox-active polypyrrole (PPy) polymers are introduced into anodic aluminum oxide (AAO) nanochannels to form smart unipolar nanofluidic diodes (UNDs) for the first time.The ionic transport behavior of the present polypyrrole-engineered UNDs can be controlled through the redox reactions of PPy.Under an applied oxidation potential,conductive PPy exhibits several redox states carrying different charges,following the formation of polarons and bipolarons with different oxidation states.Combined with the asymmetric distribution of PPy in the AAO nanochannels,the UNDs investigated here exhibit redox-switchable ion rectification and ion-gating properties.The influence of the charge asymmetry of the UNDs on their ionic transport behavior is assessed by precisely controlling the length of oxidized PPy segments in the AAO nanochannels and by carrying out theoretical simulations based on the Poisson and Nernst-Planck (PNP) equations.     

Anomalous ion transport in 2-nm hydrophilic nanochannels

Transmembrane proteins often contain nanoscale channels through which ions and molecules can pass either passively (by diffusion) or actively (by means of forced transport). These proteins play important roles in selective mass transport and electrical signalling in many biological processes. Fluidic nanochannels that are 1-2 nm in diameter act as functional mimics of protein channels, and have been used to explore the transport of ions and molecules in confined liquids. Here we report ion transport in 2-nm-deep nanochannels fabricated by standard semiconductor manufacturing processes. Ion transport in these nanochannels is dominated by surface charge until the ion concentration exceeds 100 mM. At low concentrations, proton mobility increases by a factor of four over the bulk value, possibly due to overlapping of the hydrogen-bonding network of the two hydration layers adjacent to the hydrophilic surfaces. The mobility of K+/Na+ ions also increases as the bulk concentration decreases, although the reasons for this are not completely understood.     

Wettability and Applications of Nanochannels

Wettability in nanochannels is of great importance for understanding many challenging problems in interface chemistry and fluid mechanics, and presents versatile applications including mass transport, catalysis, chemical reaction, nanofabrication, batteries, and separation. Recently, both molecular dynamic simulations and experimental measurements have been employed to study wettability in nanochannels. Here, wettability in three types of nanochannels comprising 1D nanochannels, 2D nanochannels, and 3D nanochannels is summarized both theoretically and experimentally. The proposed concept of “quantum‐confined superfluid” for ultrafast mass transport in nanochannels is first introduced, and the mostly studied 1D nanochannels are reviewed from molecular simulation to water wettability, followed by reversible switching of water wettability via external stimuli (temperature and voltage). Liquid transport and two confinement strategies in nanochannels of melt wetting and liquid wetting are also included. Then, molecular simulation, water wettability, liquid transport, and confinement in nanochannels are introduced for 2D nanochannels and 3D nanochannels, respectively. Based on the wettability in nanochannels, broad applications of various nanochannels are presented. Finally, the perspective for future challenges in the wettability and applications of nanochannels is discussed.     

Streaming potential effects on solute dispersion in nanochannels

This correspondence presents a theoretical analysis of the effects of streaming potential on the hydrodynamic dispersion of solutes in pressure-driven flow. The induced electroosmotic backflow is shown to significantly decrease the solute dispersion in slit nanochannels. The dispersion coefficient as traditionally defined may be significantly increased or decreased by streaming potential effects. These influences are sensitive to the solute charge, and found to be mainly dependent on an electrokinetic "figure of merit".     

A nanofluidic railroad switch for DNA

We present a metamaterial consisting of a two-dimensional, asymmetric lattice of crossed nanochannels in fused silica, with channel diameters of 80 nm to 140 nm. When DNA is introduced, it is stretched and linearized. We show that the asymmetry in channel dimensions gives rise to a preferred direction for DNA orientation and a preferred direction for transport under dc electrophoresis. Interestingly, the preferred axis of orientation and transport can be switched by 90 degrees through application of an ac voltage. We explain the results in terms of an energy landscape for polyelectrolytes that consists of entropic and dielectrophoretic contributions and whose strength and sign can be tuned by changing the ac field strength.     

Kinetic equations for non-equilibrium grain boundary segregation induced by applied tensile stress

Abstract

Based on an earlier model, a set of kinetic equations is derived to formulate the process of non-equilibrium grain boundary segregation induced by a low tensile stress. These kinetic equations allow excellent simulation of the grain boundary segregation of phosphorus and sulphur observed in steels subjected to low tensile stresses. The simulation results justify both the earlier model and the present kinetic equations. They also show that an applied tensile stress can increase the diffusion rate of solute-vacancy complexes and decrease that of isolated solute atoms significantly, and can also bring forward the critical time of non-equilibrium segregation for phosphorus and delay that for sulphur.     

Asymptotic solutions for two-site non-equilibrium transport

Summary The steepest descent method is used to ascertain the large-time behavior of solute concentrations in homogeneous porous media as determined by advection, diffusion and adsorption-desorption processes; it is found that linear non-equilibrium processes do not, asymptotically, affect the characteristic dispersion length of the transport medium.     

A charge-driven molecular water pump

Understanding and controlling the transport of water across nanochannels is of great importance for designing novel molecular devices, machines and sensors and has wide applications, including the desalination of seawater. Nanopumps driven by electric or magnetic fields can transport ions and magnetic quanta, but water is charge-neutral and has no magnetic moment. On the basis of molecular dynamics simulations, we propose a design for a molecular water pump. The design uses a combination of charges positioned adjacent to a nanopore and is inspired by the structure of channels in the cellular membrane that conduct water in and out of the cell (aquaporins). The remarkable pumping ability is attributed to the charge dipole-induced ordering of water confined in the nanochannels, where water can be easily driven by external fields in a concerted fashion. These findings may provide possibilities for developing water transport devices that function without osmotic pressure or a hydrostatic pressure gradient.