Solid-state Nanochannels Research Articles

Solid-state nanochannels for bio-marker analysis.

Bio-markers, such as ions, small molecules, nucleic acids, peptides, proteins and cells, participate in the construction of living organisms and play important roles in biological processes. It is of great significance to accurately detect these bio-markers for studying their basic functions, the development of molecular diagnosis and to better understand life processes. Solid-state nanochannel-based sensing systems have been demonstrated for the detection of bio-markers, due to their rapid, label-free and high-throughput screening, with high sensitivity and specificity. Generally, studies on solid-state nanochannels have focused on probes on the inner-wall (PIW), ignoring probes on the outer-surface (POS). As a result, the direct detection of cells is difficult to realize by these inner-wall focused nanochannels. Moreover, the sensitivity for detecting ions, small molecules, nucleic acids, peptides and proteins requires further improvement. Recent research has focused on artificial solid-state nanochannels with POS, which have demonstrated the ability to independently regulate ion transport. This design not only contributes to the in situ detection of large analytes, such as cells, but also provides promising opportunities for ultra-high sensitivity detection with a clear mechanism. In this tutorial review, we present an overview of the detection principle used for solid-state nanochannels, inner-wall focused nanochannels and outer-surface focused nanochannels. Furthermore, we discuss the remaining challenges faced by current nanochannel technologies and provide insights into their prospects.

Disentangling 1/f noise from confined ion dynamics.

Ion transport through biological and solid-state nanochannels is known to be a highly noisy process. The power spectrum of current fluctuations is empirically known to scale like the inverse of frequency, following the long-standing yet poorly understood Hooge's law. Here, we report measurements of current fluctuations across nanometer-scale two-dimensional channels with different surface properties. The structure of fluctuations is found to depend on the channel's material. While in pristine channels current fluctuations scale like 1/f1+a with a = 0-0.5, the noise power spectrum of activated graphite channels displays different regimes depending on frequency. Based on these observations, we develop a theoretical formalism directly linking ion dynamics and current fluctuations. We predict that the noise power spectrum takes the form 1/f × Schannel(f), where 1/f fluctuations emerge in fluidic reservoirs on both sides of the channel and Schannel describes fluctuations inside it. Deviations to Hooge's law thus allow direct access to the ion transport dynamics of the channel - explaining the entire phenomenology observed in experiments on 2D nanochannels. Our results demonstrate how current fluctuations can be used to characterize nanoscale ion dynamics.

Synergistic Effect of Bio-Inspired Nanochannels: Hydrophilic DNA Probes at Inner Wall and Hydrophobic Coating at Outer Surface for Highly Sensitive Detection.

During the past few decades, bio-inspired nanochannels have been well developed and applied in biosensing, energy transfer, separation, and so on. Here, inspired by the synergistic effect of biological nanopores, biomimetic solid-state nanochannels with hydrophilic DNA probes at the inner wall (DNA@IWHydrophilic ) and hydrophobic coating at the outer surface (None@OSHydrophobic ) are designed. To demonstrate their prompted sensing properties, Hg2+ and its specific probe are selected as target and hydrophilic DNA probes, respectively. Compared with the traditional solid-state nanochannels with hydrophilic probes distributed on both the inner wall and outer surface, the nanochannels with DNA@IWHydrophilic +None@OSHydrophobic significantly decrease the limit of detection (LOD) by 105 -fold. The obvious improvement of sensitivity (with LOD of 1nM) is attributed to the synergistic effect: None@OSHydrophobic results in the nanochannel's effective diameter decrease and DNA@IWHydrophilic induces a specific sensing target. Meanwhile, nanomolar detection of Hg2+ in human serum and in vivo fish muscle are achieved. Through molecular dynamics simulation, the synergistic effect can be confirmed by ion fluxes increasement;the relative carbon nanotube increases from 135.64% to 135.84%. This work improves the understanding of nanochannels' synergistic effect and provides a significant insight for nanochannels with improved sensitivity.

Mechanisms of Enzymatic Transduction in Nanochannel Biosensors.

The immobilization of enzymes in solid-state nanochannels is a new avenue for the design of biosensors with outstanding selectivity and sensitivity. This work reports the first theoretical model of an enzymatic nanochannel biosensor. The model is applied to the system previously experimentally studied by Lin, et al. (Anal. Chem. 2014, 86, 10546): a hourglass nanochannel modified by glucose oxidase for the detection of glucose. Our predictions are in good agreement with experimental observations as a function of the applied potential, pH and glucose concentration. The sensing mechanism results from the combination of three processes: i) the establishment of a steady-state proton concentration gradient due to a reaction-diffusion mechanism, ii) the effect of that gradient on the charge of the adsorbed enzymes and native surface groups, and iii) the effect of the resulting surface charge on the ionic current. Strategies to improve the sensor performance based on this mechanism are identified and discussed.

Biomimetic Nanochannels: From Fabrication Principles to Theoretical Insights.

Biological nanochannels which can regulate ionic transport across cell membranes intelligently play a significant role in physiological functions. Inspired by these nanochannels, numerous artificial nanochannels have been developed during recent years. The exploration of smart solid-state nanochannels can lay a solid foundation, not only for fundamental studies of biological systems but also practical applications in various fields. The basic fabrication principles, functional materials, and diverse applications based on artificial nanochannels are summarized in this review. In addition, theoretical insights into transport mechanisms and structure-function relationships are discussed. Meanwhile, it is believed that improvements will be made via computer-guided strategy in designing more efficient devices with upgrading accuracy. Finally, some remaining challenges and perspectives for developments in both novel conceptions and technology of this inspiring research field are stated.

Solid-State Nanochannel-Based Sensing Systems: Development, Challenges, and Opportunities

Solid-state nanochannel-based sensing systems with various structures and morphologies have realized precise measurements for various key biomarkers due to their tunable physical structures and morphologies, controllable chemical properties, and a nanoconfined space-induced target enriching effect. In the past several decades, series of solid-state nanochannel-based sensing systems mainly focused on modifying functional elements on nanochannels have allowed for a highly sensitive and specific detection of various key biomarkers between 0.1 and 100 nm, including small molecules, nucleic acids, and proteins. However, traditional solid-state nanochannel-based sensing systems have mainly focused on the functional element modified on their inner-walls (FEIW), ignoring the ion-gating effect of functional elements modified on the outer surface (FEOS). Therefore, the direct detection of targets with sizes larger than the diameters of nanochannels, i.e., cells, was hard to realize. Recently, research has turned its attention to nanochannels with FEOS, which extends the range of measurable biomarkers to cells (50 μm) and promotes precise measurements. In this Perspective, we mainly focus on exhibiting the great breakthroughs of solid-state nanochannels with distinct partitions of the inner wall (IW) and outer surface (OS). Meanwhile, the cutting-edge concept of nanochannels with quantum confined superfluid (QSF) is also discussed. A possible explanation for the ultrafast flow of liquids and gases through nanopores based on wave-particle duality was also provided. The quantum effect on ultrafast flow would provide new perspectives for nanochannel-based sensing systems for various key biomarkers, which may also promote the development of seawater desalination, energy conversion, and information systems.

Gating Effects for Ion Transport in Three-Dimensional Functionalized Covalent Organic Frameworks.

The development of bioinspired nano/subnano-sized (<2 nm) ion channels is still considered a great challenge due to the difficulty in precisely controlling pore's internal structure and chemistry. Herein, for the first time, we report that three-dimensional functionalized covalent organic frameworks (COFs) can act as an effective nanofluidic platform for intelligent modulation of the ion transport. By strategic attachment of 12-crown-4 groups to the monomers as ion-driver door locks, we demonstrate that gating effects of functionalized COFs can be activated by lithium ions. The obtained materials exhibit an outstanding selective ion transmission performance with a high gating ratio (up to 23.6 for JUC-590), which is among the highest values in metal ion-activated solid-state nanochannels reported so far. Furthermore, JUC-590 offers high tunability, selectivity, and recyclability of ion transport proved by the experimental and simulated studies.

Highly enantioselective recognition of S-ibuprofen by a host-guest induced chiral nanochannel.

Chirality is an important property, especially for chiral drug enantiomers with huge differences in pharmacology and toxicity. Chiral recognition of drug enantiomers is the first step to understanding the physiological phenomenon and ensuring medical safety. To efficiently identify and isolate these chiral drugs, we prepared a nanochannel. Here, a chiral sensor was fabricated by introducing the host-guest system of pillar[5]arene (WAP5) and phenethylamine into solid-state nanochannels. The chiral guest R-phenethylamine (R-PEA) induced the chirality of the host-guest system and amplified the chiral selectivity for ibuprofen enantiomers in the host-guest-based nanochannels, which was significantly greater than that in the aqueous phase or the R-PEA modified nanochannels. This study provides a strategy to fabricate highly enantioselective nanosensors for chiral drugs.

Solid-State Nanochannel with Multiple Signal Outputs for Furin Detection Based on the Biocompatible Condensation Reaction.

Utilizing ionic current and fluorescent dual-signal-output nanochannels to achieve the detection of specific target species has received much attention. The introduction of an optical signal could not only improve the selectivity of the detection systems, but also make it possible to observe the reduction of the ionic current that originated from stimulus-triggered nanochannel changes. However, the resolution of an optical signal can only verify issues of the presence or absence and cannot precisely analyze the detailed chemical structural changes within nanochannels. Here, we employed a biocompatible condensation reaction between 2-cyanobenzothiazole (CBT) and d-cysteine, and synthesized molecules PCTC that can be polymerized by cutting off short peptide sequences in the presence of furin to realize the detection of furin with multiple signal outputs. Through the introduction of a UV light-sensitive DNA sequence to the capture probes (CPs) inside the nanochannels, the blocking of the nanochannels can be confirmed to the formed oligomers by mass spectrometry analysis.

Bioinspired Solid-State Nanochannel Sensors: From Ionic Current Signals, Current, and Fluorescence Dual Signals to Faraday Current Signals.

Inspired from bioprotein channels of living organisms, constructing "abiotic" analogues, solid-state nanochannels, to achieve "smart" sensing towards various targets, is highly seductive. When encountered with certain stimuli, dynamic switch of terminal modified probes in terms of surface charge, conformation, fluorescence property, electric potential as well as wettability can be monitored via transmembrane ionic current, fluorescence intensity, faraday current signals of nanochannels and so on. Herein, the modification methodologies of nanochannels and targets-detecting application are summarized in ions, small molecules, as well as biomolecules, and systematically reviewed are the nanochannel-based detection means including 1) by transmembrane current signals; 2) by the coordination of current- and fluorescence-dual signals; 3) by faraday current signals from nanochannel-based electrode. The coordination of current and fluorescence dual signals offers great benefits for synchronous temporal and spatial monitoring. Faraday signals enable the nanoelectrode to monitor both redox and non-redox components. Notably, by incorporation with confined effect of tip region of a needle-like nanopipette, glorious in-vivo monitoring is conferred on the nanopipette detector at high temporal-spatial resolution. In addition, some outlooks for future application in reliable practical samples analysis and leading research endeavors in the related fantastic fields are provided.

Tailoring CO2-Activated Ion Nanochannels Using Macrocyclic Pillararenes.

Gas-responsive nanochannels have great relevance for applications in many fields. Inspired by CO2-sensitive ion channels, herein we present an approach for designing solid-state nanochannels that allow controlled regulation of ion transport in response to alternate CO2/N2 stimuli. The pillar[5]arene (P5N) bearing diethylamine groups can convert into the water-soluble host P5C, containing cationic tertiary ammonium salt groups after absorbing CO2. Subsequently, the nanochannel walls are tailored using P5N-based host-guest chemistry. The ion transport rate of K+ in the P5N nanochannels under CO2 was 1.66 × 10-4 mol h-1 m-2, whereas that under N2 was 7.98 × 10-4 mol h-1 m-2. Notably, there was no significant change to the ion current after eight cycles, which may indicate the stability and repeatability of CO2-activated ion nanochannels. It is speculated that the difference in ion conductance resulted from the change in wettability and surface charge within the nanochannels in response to the gas stimuli. Achieving CO2-activated ion transport in solid-state nanochannels opens new avenues for biomimetic nanopore systems and advanced separation processes.

Field effect control of translocation dynamics in surround-gate nanopores

Controlling the fast electrophoresis of nano-objects in solid-state nanopores is a critical issue for achieving electrical analysis of single-particles by ionic current. In particular, it is crucial to slow-down the translocation dynamics of nanoparticles. We herein report that a focused electric field and associated water flow in a surround-gate nanopore can be used to trap and manipulate a nanoscale object. We fine-control the electroosmosis-induced water flow by modulating the wall surface potential via gate voltage. We find that a nanoparticle can be captured in the vicinity of the conduit by balancing the counteracting electrophoretic and hydrodynamic drag forces. By creating a subtle force imbalance, in addition, we also demonstrate a gate-controllable motion of single-particles moving at an extremely slow speed of several tens of nanometers per second. The present method may be useful in single-molecule detection by solid-state nanopores and nanochannels.

A universal functionalization strategy for biomimetic nanochannel via external electric field assisted non-covalent interaction

Biological ion channels, as fundamental units participating in various daily behaviors with incredible mass transportation and signal transmission, triggered booming researches on manufacturing their artificial prototypes. Biomimetic ion channel with the nanometer scale for smart responding functions has been successfully realized in sorts of materials by employing state-of-art nanotechnology. Ion track-etching technology, as crucial branches of fabricating solid-state nanochannels, exhibits outstanding advantages, such as easy fabrication, low cost, and high customization. To endow the nanochannel with smart responsibility, various modification methods are developed, including chemical grafting, non-covalent adsorption, and electrochemical deposition, enriching the reservoir of accessible stimuli-responses combinations, whereas were limited by their relatively lengthy and complex procedure. Here, based on the electric field induced self-assembly of polyelectrolytes, a universal customizable modifying strategy has been proposed, which exhibits superiorities in their functionalization with convenience and compatibility. By using this protocol, the channels’ ionic transport behaviors could be easily tuned, and even the specific ionic or molecular responding could be realized with superior performance. This strategy surely accelerates the nanochannels functionalization into fast preparing, high efficiency, and large-scale application scenarios.

Effect of electrolyte concentration and symmetry on the heterogeneous surface charge in an electrically gated nanochannel

The present study aims to investigate utilizing field effect for inducing heterogeneous surface charge and consequently changing the fluid flow in a solid-state nanochannel with converging–diverging periodicity. It is shown that the combination of geometry and applied gate voltage (VG) would generate heterogeneous surface charge at the channel walls which can be modulated by VG, i.e., a moderate VG (0.7–0.9 V) causes charge inversion in diverging sections of the channel (Dmax), while VG > 0.9 enables charge inversion in the entire channel, but it is still non-uniform in each section. The results show that zeta (ζ) potential is a function of VG which shows a linear to nonlinear transition due to dilution of electrolyte in agreement with density functional theory and Monte Carlo simulations. In contrast, electrolyte symmetry has a minor effect on the variation of ζ potential. It is also shown that the difference in ζ potential across the channel (Δζ) increases by dilution of electrolyte and utilizing a more symmetric electrolyte with lower valances. For the first time, it is shown that Δζ presents a maximum with the VG. The VG corresponding to the maximum Δζ decreases with both dilution of electrolyte and higher anion valance. This is of practical importance to overcome leakage current problem of field-effect fluidic devices. It is also shown that the velocity field can be altered by changing both electrolyte concentration and symmetry. However, applying VG was found to be a more efficient way than electrolyte modifications. This includes generating circulation inside the channel which is of prime importance for applications such as mixing or separation/trapping.

Polyaniline for Improved Blue Energy Harvesting: Highly Rectifying Nanofluidic Diodes Operating in Hypersaline Conditions via One-Step Functionalization

Solid-state nanochannels have attracted substantial attention of the scientific community due to their remarkable control of ionic transport and the feasibility to regulate the iontronic output by different stimuli. Most of the developed nanodevices are subjected to complex modification methods or show functional responsiveness only in moderate-ionic-strength solutions. Within this project, we present a nanofluidic device with enhanced ionic current rectification properties attained by a simple one-step functionalization of single bullet-shaped polyethylene terephthalate (PET) nanochannels with polyaniline (PANI) that can work in high-ionic-strength solutions. The integration of PANI also introduces a broad pH sensitivity, which makes it possible to modulate the ionic transport behavior between anion-selective and cation-selective regimes depending on the pH range. Since PANI is an electrochemically active polymer, ionic transport also becomes dependent on the presence of redox stimuli in solution. We demonstrate that PANI-functionalized single-nanochannel membranes function as an efficient salinity gradient-based energy conversion device even in acidic concentrated salt solutions, opening the door to applications under a variety of novel operating conditions.

Fabrication of a Biomimetic Nanochannel Logic Platform and Its Applications in the Intelligent Detection of miRNA Related to Liver Cancer.

Nanochannel-based analytical techniques have great potential applications for nucleic acid sequencing and high sensitivity detection of biological molecules. However, the sensitivity of conventional solid-state nanochannel sensors is hampered by a lack of effective signal amplification strategies, which has limited its utility in the field of analytical chemistry. Here we selected a solid-state nanochannnel modified with polyethylenimine and Zr4+ in combination with graphene oxide as the sensing platform. The high-performance sensor is based upon the change of the surface charge of the nanochannel, which is resulted from DNA cascade signal amplification in solution. The target miRNA (miR-122) can be indirectly quantitated with a detection limit of 97.2 aM with an excellent selectivity. Depending on the nucleic acid's hybridization and configuration transform, the designed nanochannel sensing systems can realize the intelligent detection of multiple liver cancer-related miRNA (miR-122 and miR Let-7a) integrating with cascaded INHIBIT-OR logic gate to provide theoretical guidance and technical support for clinical diagnosis and therapeutic evaluation of liver cancer.

Voltage-Triggered Structural Switching of Polyelectrolyte-Modified Nanochannels

Synthetic solid-state nanochannels modified with polyelectrolyte brushes are an important class of stimuli-responsive nanofluidic devices. This work theoretically addresses the design of a voltage-...

Dimension-reconfigurable bubble film nanochannel for wetting based sensing

Dimensions and surface properties are the predominant factors for the applications of nanofluidic devices. Here we use a thin liquid film as a nanochannel by inserting a gas bubble in a glass capillary, a technique we name bubble-based film nanofluidics. The height of the film nanochannel can be regulated by the Debye length and wettability, while the length independently changed by applied pressure. The film nanochannel behaves functionally identically to classical solid state nanochannels, as ion concentration polarizations. Furthermore, the film nanochannels can be used for label-free immunosensing, by principle of wettability change at the solid interface. The optimal sensitivity for the biotin-streptavidin reaction is two orders of magnitude higher than for the solid state nanochannel, suitable for a full range of electrolyte concentrations. We believe that the film nanochannel represents a class of nanofluidic devices that is of interest for fundamental studies and also can be widely applied, due to its reconfigurable dimensions, low cost, ease of fabrication and multiphase interfaces.

Nanochannels of Covalent Organic Frameworks for Chiral Selective Transmembrane Transport of Amino Acids.

Mimicking cellular transport mechanisms to make solid-state smart nanochannels has long been of great interest for their diverse applications, but it poses a critical synthetic challenge. Covalent organic frameworks (COFs) are porous crystalline materials with tailor-made nanochannels and hold great potential for ion and molecule transport. We demonstrate here for the first time that 2D COFs possess the necessary merits to be promising solid-state nanochannels for selective transport of amino acids, which are the basis for life. By imine condensations of a C3-symmetric trialdehyde and a mixture of diamines with and without divinyl groups, two vinyl-functionalized 2D COFs are crystallized. Both multivariant COFs afford straight 1D mesoporous channels formed by AA or AB stacking of layered hexagonal networks. After postmodification with chiral β-cyclodextrin (β-CD) via thiol-ene click reactions, the COFs are further fabricated into free-standing mixed matrix membranes (MMMs) that can selectively transport amino acids, as revealed by monitoring not only transmembrane ionic current signature but also concentration changes of permeated substrates. Specially, in the membrane system, the AA stacked COF exhibits higher chiral recognition capability toward histidine enantiomers than the AB stacked COF because of its uniform open channels decorated with β-CD. This work highlights the great potential of COF nanochannels as a platform for accumulating functional groups for selective transport of small molecules and even biomolecules in the solid state.

Amine-Phosphate Specific Interactions within Nanochannels: Binding Behavior and Nanoconfinement Effects

In the last years, the ionic conductance behavior of solid-state nanochannels (SSN) has been extensively studied with both basic and applied purposes. In particular, the interactions between confin...