Stimuli-Responsive Ion Transport Regulation in Nanochannels by Adhesion-Induced Functionalization of Macroscopic Outer Surface.

Responsive regulation of ion transport through nanochannels is crucial in the design of smart nanofluidic devices for sequencing, sensing, and water-energy nexus. Functionalization of the inner wall of the nanochannel enhances interaction with ions and fluid but restricts versatile chemical approaches and accurate characterizations of fluidic interfaces. Herein, we reveal a responsive regulating mechanism of ion transport through nanochannels by polydopamine (PDA)-induced functionalization on the macroscopic outer surface of nanochannels. Responsive molecules were codeposited with PDA on the outer surface of nanochannels and formed a valve of nanometer thickness to manually manipulate ion transport by changing its gap spacing, surface charge, and wettability under external stimulus. The response ratio can be up to 100-fold by maximizing the proportion of responsive molecules on the outer surface. Laminating the codepositions of different responsive molecules with PDA on the channel's outer surface produces multiple responses. A nearly universal adhesion of PDA with responsive molecules on the open outer surface induces nanochannels responsive to different external stimuli with variable response ratios and arbitrary combinations. The results challenge the primary role of functionalization on the nanoconfined interface of nanofluidics and open opportunities for developing new-style nanofluidic devices through the functionalization of macroscopic interface.

Addressing Challenges in Ion-Selectivity Characterization in Nanopores.

Ion selectivity is the basis for designing smart nanopore/channel-based devices, e.g., ion separators and biosensors. Quantitative characterization of ion selectivities in nanopores often employs the Nernst or Goldman-Hodgkin-Katz (GHK) equation to interpret transmembrane potentials. However, the direction of the measured transmembrane potential drop is not specified in these equations, and selectivity values calculated using absolute values of transmembrane potentials do not directly reveal the ion for which the membrane is selective. Moreover, researchers arbitrarily choose whether to use the Nernst or GHK equation and overlook the significant differences between them, leading to ineffective quantitative comparisons between studies. This work addresses these challenges through (a) specifying the transmembrane potential (sign) and salt concentrations in terms of working and reference electrodes and the solutions in which they reside when using the Nernst and GHK equations, (b) reporting of both Nernst-selectivity and GHK-selectivity along with solution compositions and transmembrane potentials when comparing different nanopores/channels, and (c) performing simulations to define an ideal selectivity for nanochannels. Experimental and modeling studies provide significant insight into these fundamental equations and guidelines for the development of nanopore/channel-based devices.

Pore-Size-Dependent Role of Functional Elements at the Outer Surface and Inner Wall in Single-Nanochannel Biosensors.

Biological nanopores feature functional elements on the outer surfaces (FEOS) and inner walls (FEIW), enabling precise control over ions and molecules with exceptional sensitivity and specificity. This provides valuable inspiration to scientists for the development of intelligent artificial nanochannel-based platforms, with a wide range of potential applications, including biosensors. Much effort has been dedicated to investigating the distinct contribution of FEOS and FEIW of multichannel membrane biosensors. However, the intricate interactions among neighboring pores in multichannel biosensors have presented challenges. This underscores the untapped potential of single nanochannels as ideal candidates in this field. Here, we employed single nanochannel membranes with different pore sizes to investigate the distinct contributions of FEIW and FEOS to single-nanochannel biosensors, combined with numerical simulations. Our findings revealed that alterations in the negative charges of FEIW and FEOS, induced by target binding, have differential effects on ion transport, contingent upon the degree of nanoconfinement. In the case of smaller pores, such as 20 nm, the ion concentration polarization driven by FEIW can independently control ion transport through the surface's electric double layer. However, as the pore size increases to 40-60 nm, both FEIW and FEOS become essential for effective ion concentration polarization. When the pore size reaches 100 nm, both FEIW and FEOS are ineffective and thus unsuitable for biosensors. Simulations demonstrate that the observed phenomena can be attributed to the interactions between the charges of FEIW and FEOS within the overlapping electric double layer under confinement. These results underscore the critical role of pore size as a key parameter in governing the functionality of probes within or on nanopore-based biosensors as well as in the design of nanopore-based devices.

Local Electric Potential-Driven Nanofluidic Ion Transport for Ultrasensitive Biochemical Sensing.

Nanofluidic biosensors have been widely used for detection of analytes based on the change of system resistance before and after target-probe interactions. However, their sensitivity is limited when system resistance barely changes toward low-concentration targets. Here, we proposed a strategy to address this issue by means of target-induced change of local membrane potential under relatively unchanged system resistance. The local membrane potential originated from the directional diffusion of photogenerated carriers across nanofluidic biosensors and gated photoinduced ionic current signal before and after target-probe interactions. The sensitivity of such biosensors for the detection of biomolecules such as circulating tumor DNA (ctDNA) and lysozyme exceeds that of applying a traditional strategy by more than 3 orders of magnitude under unchanged system resistance. Such biosensors can specifically detect the small molecule biomarker in the blood sample between prostate cancer patients and healthy humans. The key advantages of such nanofluidic biosensors are therefore complementary to traditional nanofluidic biosensors, with potential applications in a point-of-care analytical tool.

Role of Outer Surface Probes on Bullet-Shaped Asymmetric Solid-State Nanochannels for Lysozyme Protein Sensing.

Artificial solid-state nanochannels featuring precise partitions present a highly promising platform for biomarker detection. While the significance of probes on the outer surface (POS) has been relatively overlooked in the past, our research highlights their crucial role in biosensing. Furthermore, the contribution of POS on the bullet-shaped asymmetric nanochannels has not been extensively explored until now. Here, we fabricated a series of bullet-shaped nanochannels, each featuring a distinct asymmetric structure characterized by different tip- and base-pore diameters. These nanochannels were further modified with explicit distributions at the inner wall (PIW), the outer surface (POS), and their combination (POS + PIW) for lysozyme sensing. The impact of diameters, structural asymmetry, and surface charge density on the sensing efficacy of POS and PIW was thoroughly examined through experimental investigations and numerical simulations. POS demonstrates great individual sensing performance for lysozyme within a broad concentration range, spanning from 10 nM to 1 mM. Furthermore, it improves the sensitivity when combined with PIW, particularly within the nanochannels featuring the smaller base-pore diameter, resulting in a 2-fold increase in sensing performance for POS + PIW compared to PIW at a concentration of 10 nM. These findings are substantiated by numerical simulations that closely align with the experimental parameters. The contributions of POS are notably amplified in the presence of smaller base pores and a higher degree of asymmetry within the bullet-shaped nanochannels. These findings elucidate the mechanism underlying the role of POS within bullet-shaped asymmetric nanochannels and open up new avenues for manipulating and enhancing the sensing efficiency.

Bogoliubov polaritons mediated strong indirect interaction between distant whispering-gallery-mode resonators.

We propose a method to achieve a strong indirect interaction between two distant whispering-gallery-mode (WGM) resonators in a hybrid quantum system at room temperature, even when the distance between them exceeds 40 wavelengths. By exploiting the quantum critical point, we can greatly enhance both the effective damping rate and the coupling strengths between a WGM resonator and a low-frequency polariton. We introduce a large effective frequency detuning to suppress the effective damping rate while maintaining the enhanced coupling strength. The strong indirect interaction between separated WGM resonators is mediated by a far-off-resonant low-frequency polariton through virtual excitations in a process similar to Raman process. This proposal provides a viable approach to building a quantum network based on strongly coupled WGM resonators.

Enzyme Regulating the Wettability of the Outer Surface of Nanochannels.

Functional probes not only at the inner wall but also at the outer surface of nanochannel systems could be used for the recognition and detection of biotargets. Despite the advancements, the current detection mechanisms are still mainly based on the surface charge variation. We proposed a strategy of using the variation of wettability on the outer surface of nanochannels for detecting a tumor marker, herein, exemplifying matrix metalloproteinase-2 (MMP-2). The outer surface of the nanochannels were modified with amphipathic peptide probe consisting of hydrophilic unit (CRRRR), MMP-2 cleavage unit (PLGLAG), and hydrophobic unit (Fn). After recognition of MMP-2, due to the release of hydrophobic unit, the hydrophilicity of the outer surface was expected to increase, thus leading to the increase of ion current. Furthermore, the number (n) of phenylalanine (F) in the hydrophobic unit was modulated from 2, 4, to 6. By lengthening the hydrophobic unit, the limit of detection for MMP-2 detection could reach 1 ng/mL (when n = 6) and improve by 50-fold (to n = 2). This nanochannel system was utilized to successfully detect the MMP-2 secreted from cells and demonstrated that the expression of MMP-2 was related to the cell cycle and exhibited the highest level in G1/S phase. This study proved that in addition to the surface charge, wettability regulation could also be utilized as a variation factor to broaden the design strategy of a probe on OS to achieve the detection of biotargets.

Polydopamine-Induced Modification on the Highly Charged Surface of Asymmetric Nanofluidics: A Strategy for Adjustable Ion Current Rectification Properties.

Surface charge effects in nanoconfines is one of the fundamentals in the ion current rectification (ICR) of nanofluidics, which provides entropic driving force by asymmetric surface charges and causes ion enrichment/depletion by the electrostatic interaction of fixed surface charges. However, the surface charge effect causes a significant electrostatic repulsion in nanoconfines, restricting additional like charge or elaborate chemistry on the highly charged confined surface, which limits ICR manipulation. Here, we use polydopamine (PDA), a nearly universal adhesive, that adheres to the highly positive-charged poly(ethyleneimine) (PEI) gel network in a nanochannel array. PDA enhances the ICR effect from a low rectification ratio of 9.5 to 92.6 by increasing the surface charge and hydrophobicity of the PEI gel network and, meanwhile, shrinking its gap spacing. Theoretical and experimental results demonstrate the determinants of the fixed surface charge in the enrichment/depletion region on ICR properties, which is adjustable by PDA-induced change in a nanoconfined environment. Chemically active PDA brings Au nanoparticles by chloroauric reduction for further hydrophobization and the modification of negative-charged DNA complexes in nanochannels, whereby ICR effects can be manipulated in versatile means. The results describe an adjustable and versatile strategy for adjusting the ICR behaviors of nanofluidics by manipulating local surface charge effects using PDA.

Ionic Signal Enhancement by the Space Charge Effect through the DNA Rolling Circle Amplification on the Outer Surface of Nanochannels.

DNA species are recognized as a powerful probe for nanochannel analyses to address the issues of specific target recognition and highly efficient signal conversion due to their programmable and predictable Watson-Crick bases. However, in the conventional view, abundant sophisticated DNA structures synthesized by DNA amplification strategies are unsuitable for use in nanochannel analyses owing to their low probability to enter a nanochannel restricted by the smaller opening of the nanochannel, as well as the faint ion signal produced by the steric effect. Here, we present an integrated strategy of nanochannel analyses that combines the target recognitions by encoded rolling circle amplification (RCA) in solution and the ionic signal enhancement by the space charge effect through the immobilization of highly negative-charged RCA amplicons on the outer surface of the nanochannels. Owing to the highly negative-charged RCA amplicons with 100 nm sizes, a sharp increase of ionic current up to 7454% has been achieved. The RCA amplicon triggered by mRNA-21 on the outer surface of the poly(ethylene terephthalate) membrane with a single nanochannel realized the single-base mismatch detection of mRNA-21 with a sensitivity of 6 fM. The DNA amplicon endows the nanochannel with high sensitivity and selectivity that could extend to other applications, such as DNA sequencing, desalination, sieving, and water-energy nexus.

Exponential Increase in an Ionic Signal: A Dominant Role of the Space Charge Effect on the Outer Surface of Nanochannels.

Nanochannels have advantage in sensitive analyses due to the confinement effects on ionic signal in nano- or sub-nanometric confines but could realize further gains by optimizing signal mechanism. Making target recognitions on the outer surface of nanochannels has been verified to improve target recognitions and signal conversions by maximizing surfaces accessible to targets and ions, but until recently, the signal mechanism has been still unclear. Using electroneutral peptide nucleic acid (PNA) and negative-charged DNA, we verified a dominant space charge effect on an ionic signal on the outer surface of nanochannels. A typical exponential increase of the ionic signal with the charge density on the outer surface has been demonstrated through the PNA-PNA, PNA-DNA, DNA-DNA hybrid, DNA cleavage, and hybridization chain reaction. These results challenge the essential role of steric hindrance on the ionic signal and describe a new ion passageway surrounded and accelerated by the stern layer of charged species on the nanochannel outer surface.

Effective medium theory for photonic crystals with quadrupole resonances.

An effective medium theory is proposed to characterize two-dimensional dielectric photonic crystals (PCs) exhibiting quadrupole resonances. In addition to the effective permittivity and permeability associated with electric and magnetic dipoles, we obtain a local effective parameter to describe the contributions of quadrupole resonances by taking the low frequency limit of multiple-scattering theory. These effective parameters can be used to predict the characteristics of double-Dirac-cone PCs, showing good agreement with the numerical results. Moreover, we show that, after introducing the new effective parameter, the double-Dirac-cone PCs can be regarded as a generalization of the traditional double-zero-index metamaterials.

Revealing Ionic Signal Enhancement with Probe Grafting Density on the Outer Surface of Nanochannels.

Probe-modified nanopores/nanochannels are one of the most advanced sensors because the probes interact strongly with ions and targets in nanoconfinement and create a sensitive and selective ionic signal. Recently, ionic signals have been demonstrated to be sensitive to the probe-target interaction on the outer surface of nanopores/nanochannels, which can offer more open space for target recognition and signal conversion than nanoconfined cavities. To enhance the ionic signal, we investigated the effect of grafting density, a critical parameter of the sensing interface, of the probe on the outer surface of nanochannels on the change rate of the ionic signal before and after target recognition (ß). Electroneutral peptide nucleic acids and negatively charged DNA are selected as probes and targets, respectively. The experimental results showed that when adding the same number of targets, the ß value increased with the probe grafting density on the outer surface. A theoretical model with clearly defined physical properties of each probe and target has been established. Numerical simulations suggest that the decrease of the background current and the aggregation of targets at the mouth of nanochannels with increasing probe grafting density contribute to this enhancement. This work reveals the signal mechanism of probe-target recognition on the outer surface of nanochannels and suggests a general approach to the nanochannel/nanopore design leading to sensitivity improvement on the basis of relatively good selectivity.

Exploring the contribution of charged species at the outer surface to the ion current signal of nanopores: a theoretical study.

Nanopores attached to charged species realize the artificial regulation of ion transport by the electrostatic effect in nanoconfines, produce a sensitive ion current signal and play a critical role in nanopore-based analyses. However, until now, the contribution of the charged species at the outer surface, an inherent component of nanopores, to the ion current signal has not yet been fully investigated. Here, we theoretically investigate the contribution of the charged species at the outer surface to the ion current signal of a conical nanopore. The results indicate that when the electrostatic effect at the tip of the conical nanopore is strengthened, the contribution from the charged species at the outer surface to the ionic current signal becomes stronger or even predominant compared with that of the inner walls. This effect can be further enhanced using nanopore arrays with small openings and low pore density in a low concentration electrolyte. This work focuses on the working mechanism of nanopores with a high-efficient signal conversion and promotes the performance of nanopores with a regional distribution of charged probes and targets.

Towards explicit regulating-ion-transport: nanochannels with only function-elements at outer-surface.

Function elements (FE) are vital components of nanochannel-systems for artificially regulating ion transport. Conventionally, the FE at inner wall (FEIW) of nanochannel-systems are of concern owing to their recognized effect on the compression of ionic passageways. However, their properties are inexplicit or generally presumed from the properties of the FE at outer surface (FEOS), which will bring potential errors. Here, we show that the FEOS independently regulate ion transport in a nanochannel-system without FEIW. The numerical simulations, assigned the measured parameters of FEOS to the Poisson and Nernst-Planck (PNP) equations, are well fitted with the experiments, indicating the generally explicit regulating-ion-transport accomplished by FEOS without FEIW. Meanwhile, the FEOS fulfill the key features of the pervious nanochannel systems on regulating-ion-transport in osmotic energy conversion devices and biosensors, and show advantages to (1) promote power density through concentrating FE at outer surface, bringing increase of ionic selectivity but no obvious change in internal resistance; (2) accommodate probes or targets with size beyond the diameter of nanochannels. Nanochannel-systems with only FEOS of explicit properties provide a quantitative platform for studying substrate transport phenomena through nanoconfined space, including nanopores, nanochannels, nanopipettes, porous membranes and two-dimensional channels.

Revealing the Critical Role of Probe Grafting Density in Nanometric Confinement in Ionic Signal via an Experimental and Theoretical Study.

The grafting density of probes at sensor interface plays a critical role in the performance of biochemical sensors. However, compared with macroscopic interface, the effects of probe grafting density at nanometric confinement are rarely studied due to the limitation of precise grafting density regulation and characterization at the nanoscale. Here, we investigate the effect from the grafting density of DNA probes on ionic signal for nucleic acid detection in a cylindrical nanochannel array (with diameter of 25 nm) by combing experiments and theories. We set up a theoretical model of charge distribution from close to inner wall of nanochannels at low probe grafting density to spreading in whole space at high probe grafting density. The theoretical results fit well with the experimental results. A reverse of ionic output from signal-off to signal-on occurs with increasing probe grafting density. Low probe grafting density offers a high current change ratio that is further enhanced using long-chain DNA probes or the electrolyte with a low salt concentration. This work develops an approach to enhance performance of nanochannel-based sensors and explore physicochemical properties in nanometric confines.

Bilayer fractal structure with multiband left-handed characteristics.

We present a bilayer fractal structure for the realization of multiband left-handed metamaterial at terahertz frequencies. The structure is composed of metallic H-fractal pairs separated by a dielectric layer. The electromagnetic properties of periodic H-fractal pairs have been investigated by numerical simulation. The period in the propagation direction is extremely small as compared to the wavelength at the operational frequency. Under the electromagnetic wave normal incidence, the material exhibits negative refraction simultaneously around the frequencies of 0.10 and 0.15 THz for parallel polarization, and around the frequencies of 0.19 and 0.38 THz for perpendicular polarization. The design provides a left-handed metamaterial suitable for multiband and compact devices at terahertz frequencies.