Single-Digit Nanobubble Sensing via Nanopore Technology.

Nanobubbles play an important role in diverse fields, including engineering, medicine, and agriculture. Understanding the characteristics of individual nanobubbles is essential for comprehending fluid dynamics behaviors and advancing nanoscale science across various fields. Here, we report a strategy based on nanopore sensors for characterizing single-digit nanobubbles. We investigated the sizes and diffusion coefficients of nanobubbles at different voltages. Additionally, the finite element simulation and molecular dynamics simulation were introduced to account for counterion concentration variation around nanobubbles in the nanopore. In particular, the differences in stability and surface charge density of nanobubbles under various solution environments have been studied by the ion-stabilized model and the DLVO theory. Additionally, a straightforward method to mitigate nanobubble generation in the bulk for reducing current noise in nanopore sensing was suggested. The results hold significant implications for enhancing the understanding of individual nanobubble characterizations, especially in the nanofluid field.

Electroosmotic Sensing of Uncharged Peptides and Differentiating Their Phosphorylated States Using Nanopores.

The correct characterization and identification of different kinds of proteins is crucial for the survival and development of living organisms, and proteomics research promotes the analysis and understanding of future genome functions. Nanopore technique has been proved to accurately identify individual nucleotides. However, accurate and rapid protein sequencing is difficult due to the variability of protein structures that contains more than 20 amino acids, and it remains very challenging especially for uncharged peptides as they can not be electrophoretically driven through the nanopore. Graphene nanopores have the advantages of high accuracy, sensitivity and low cost in identifying protein phosphorylation modifications. Here, by using all-atom molecular dynamics simulations, charged graphene nanopores are employed to electroosmotically capture and sense uncharged peptides. By further mimicking AFM manipulation of single molecules, it is also found that the uncharged peptides and their phosphorylated states could also be differentiated by both the ionic current and pulling force signals during their pulling processes through the nanopore with a slow and constant velocity. The results shows ability of using nanopores to detect and discriminate single amino acid and its phosphorylation, which is essential for the future low-cost and high-throughput sequencing of protein residues and their post-translational modifications.

Protein Deceleration and Sequencing Using Si3N4-CNT Hybrid Nanopores.

Protein sequencing is crucial for understanding the complex mechanisms driving biological functions and is of utmost importance in molecular diagnostics and medication development. Nanopores have become an effective tool for single molecule sensing, however, the weak charge and non-uniform charge distribution of protein make capturing and sensing very challenging, which poses a significant obstacle to the development of nanopore-based protein sequencing. In this study, to facilitate capturing of the unfolded protein, highly charged peptide was employed in our simulations, we found that the velocity of unfolded peptide translocating through a hybrid nanopore composed of silicon nitride membrane and carbon nanotube is much slower compared to bare silicon nitride nanopore, it is due to the significant interaction between amino acids and the surface of carbon nanotube. Moreover, by introducing variations in the charge states at the boundaries of carbon nanotube nanopores, the competition and combination of the electrophoretic and electroosmotic flows through the nanopores could be controlled, we then successfully regulated the translocation velocity of unfolded proteins through the hybrid nanopores. The proposed hybrid nanopore effectively retards the translocation velocity of protein through it, facilitates the acquisition of ample information for accurate amino acid identification.

Conformation Influence of DNA on the Detection Signal through Solid-State Nanopores.

The detection and identification of nanoscale molecules are crucial, but traditional technology comes with a high cost and requires skilled operators. Solid-state nanopores are new powerful tools for discerning the three-dimensional shape and size of molecules, enabling the translation of molecular structural information into electric signals. Here, DNA molecules with different shapes were designed to explore the effects of electroosmotic forces (EOF), electrophoretic forces (EPF), and volume exclusion on electric signals within solid-state nanopores. Our results revealed that the electroosmotic force was the main driving force for single-stranded DNA (ssDNA), whereas double-stranded DNA (dsDNA) was primarily dominated by electrophoretic forces in nanopores. Moreover, dsDNA caused greater amplitude signals and moved faster through the nanopore due to its larger diameter and carrying more charges. Furthermore, at the same charge level and amount of bases, circular dsDNA exhibited a tighter structure compared to brush DNA, resulting in a shorter length. Consequently, circular dsDNA caused higher current-blocking amplitudes and faster passage speeds. The characterization approach based on nanopores allows researchers to get molecular information about size and shape in real time. These findings suggest that nanopore detection has the potential to streamline nanoscale characterization and analysis, potentially reducing both the cost and complexity.

Unfolding of protein using MoS2/SnS2heterostructure for nanopore-based sequencing.

Protein sequencing is crucial for understanding the complex mechanisms driving biological functions. However, proteins are usually folded in their native state and the mechanism of fast protein conformation transitions still remains unclear, which make protein sequencing challenging. Molecular dynamics simulations with accurate force field are now able to observe the entire folding/unfolding process, providing valuable insights into protein folding mechanisms. Given that proteins can be unfolded, nanopore technology shows great potential for protein sequencing. In this study, we proposed to use MoS2/SnS2heterostructures to firstly unfold proteins and then detect them by a nanopore in the heterostructural membrane. All-atom molecular dynamics simulations performed in this work provided rich atomic-level information for a comprehensive understanding of protein unfolding process and mechanism on the MoS2/SnS2heterostructure, it was found that the strong binding of protein to SnS2nanostripe and hydrogen bond breaking were the main reasons for unfolding the protein on the heterostructure. After the protein was fully unfolded, it was restrained on the nanostripe because of the affinity of protein to the SnS2nanostripe. Thus by integrating the proposed unfolding technique with nanopore technology, detection of linear unfolded peptide was realized in this work, allowing for the identification of protein components, which is essential for sequencing proteins in the near future.

Trapping and recapturing single DNA molecules with pore-cavity-pore device.

Single-molecule detection technology is a technique capable of detecting molecules at the single-molecule level, characterized by high sensitivity, high resolution, and high specificity. Nanopore technology, as one of the single-molecule detection tools, is widely used to study the structure and function of biomolecules. In this study, we constructed a small-sized nanopore with a pore-cavity-pore structure, which can achieve a higher reverse capture rate. Through simulation, we investigated the electrical potential distribution of the nanopore with a pore-cavity-pore structure and analyzed the influence of pore size on the potential distribution. Accordingly, different pore sizes can be designed based on the radius of gyration of the target biomolecules, restricting their escape paths inside the chamber. In the future, nanopores with a pore-cavity-pore structure based on two-dimensional thin film materials are expected to be applied in single-molecule detection research, which provides new insights for various detection needs.

DNA Carrier-Assisted Molecular Ping-Pong in an Asymmetric Nanopore.

Nanopore analysis relies on ensemble averaging of translocation signals obtained from numerous molecules, requiring a relatively high sample concentration and a long turnaround time from the sample to results. The recapture and subsequent re-reading of the same molecule is a promising alternative that enriches the signal information from a single molecule. Here, we describe how an asymmetric nanopore improves molecular ping-pong by promoting the recapture of the molecule in the trans reservoir. We also demonstrate that the molecular recapture could be improved by linking the target molecule to a long DNA carrier to reduce the diffusion, thereby achieving over 100 recapture events. Using this ping-pong methodology, we demonstrate its use in accurately resolving nanostructure motifs along a DNA scaffold through repeated detection. Our method offers novel insights into the control of DNA polymer dynamics within nanopore confinement and opens avenues for the development of a high-fidelity DNA detection platform.

Detection of DNA translocations in a nanopore series circuit using a current clamp.

The advancement of nanopore sensing technology over the past 20 years has been impressive, particularly in the field of nucleic acid sequencing, which has already been used in commercial diagnostic tests. A traditional configuration of nanopore sensing records the current through a single nanopore using a voltage clamp, which hits a bottleneck in expanding its functions, while integrating several nanopores to build a nanopore circuit may be an effective solution. Here, we report a new strategy combining a nanopore series circuit and a current clamp to record the current signal and the voltage signal of DNA translocation through a nanopore simultaneously, which could increase the fidelity of event analysis. We observed a capacitor-like charging and discharging behavior in the voltage signals and proposed a detailed microscopic mechanism to elucidate it. Our strategy could benefit the development of nanopore technology and contribute to understanding the working principles of the units in a nanopore circuit system.

A controllable nanoscale telescopic arm designed by encoding the nested multi-walled carbon nanotubes.

Micro/nano manipulation technologies have shown enormous potential in the field of accurate surgery, which is expected to promote the development of precision medicine. Therefore, scientists have been devoted to designing and manipulating nanoscale devices and tools which can conduct surgical functions, such as penetration, drilling and cleaving targeting either single cells or biological tissues. To enrich the functionality of the family of nanomachines, a theoretical nanoscale telescopic arm manipulated by charge-tunable multi-walled carbon nanotubes is designed in this work. By using predesigned encoding strategies that could periodically alternate the external electric fields and surface charge densities of the nanorings embedded in the carbon nanotubes, well controlled manipulations of the telescopic arm are realized in MD simulations to mimic nanoscale surgeries. The telescopic arm can stretch out by the external electric force and draw back by vdW attraction between the nested nanotubes. Meanwhile, the electric double layer formed around the nanoring area in the nanotube is used as a brake during the retraction process to make the nanotube halt stably at the target position. The working distance could also be tuned by changing the number of the nested nanotubes, which presents a promising avenue for varieties of biomedical applications.

Length-Dependent Collective Vibrational Dynamics in Alpha-Helices.

The front cover artwork is provided by Prof. Yunfei Chen's group at the Southeast University. The image shows collective vibrational motions of alpha-helices inside a protein. Studying the vibrations allows connecting protein structure and function, and therefore benefits de novo protein design. Read the full text of the Research Article at 10.1002/cphc.202200082.

Length-Dependent Collective Vibrational Dynamics in Alpha-Helices.

Functions of protein molecules in nature are closely associated with their well-defined three-dimensional structures and dynamics in body fluid. So far, many efforts have been made to reveal the relation of protein structure, dynamics, and function, but the structural origin of protein dynamics, especially for secondary structures as building blocks of conformation transition, is still ambiguous. Here we theoretically uncover the collective vibrations of elastic poly-alanine α-helices and find vibration patterns that are distinctively different over residue numbers ranging from 20 to 80. Contrary to the decreasing vibration magnitude from ends to the middle region for short helices, the vibration magnitude for long helices takes the minimum at approximately 1/5 of helix length from ends but reaches a peak at the center. Further analysis indicates that major vibrational modes of helical structures strongly depend on their lengths, where the twist mode dominates in the vibrations of short helices while the bend mode dominates the long ones analogous to an elastic Euler beam. The helix-coil transition pathway is also affected by the alternation of the first-order mode in helices with different lengths. The dynamic properties of the helical polypeptides are promising to be harnessed for de novo design of protein-based materials and artificial biomolecules in clinical treatments.

Fabrication of solid-state nanopores.

Nanopores are valuable single-molecule sensing tools that have been widely applied to the detection of DNA, RNA, proteins, viruses, glycans, etc. The prominent sensing platform is helping to improve our health-related quality of life and accelerate the rapid realization of precision medicine. Solid-state nanopores have made rapid progress in the past decades due to their flexible size, structure and compatibility with semiconductor fabrication processes. With the development of semiconductor fabrication techniques, materials science and surface chemistry, nanopore preparation and modification technologies have made great breakthroughs. To date, various solid-state nanopore materials, processing technologies, and modification methods are available to us. In the review, we outline the recent advances in nanopores fabrication and analyze the virtues and limitations of various membrane materials and nanopores drilling techniques.

Directional passive transport of nanodroplets on general axisymmetric surfaces.

Rapid removal of small-sized droplets passively using fixed structures is a key challenge for various applications including anti-icing, rapid cooling, and water harvesting. In this work, we investigate the directional motion of nanodroplets on axisymmetric surfaces with curvature gradient through molecular dynamics (MD) simulations. It is found that as the shape of the axisymmetric surface is changed from a dome to a trumpet, the droplet velocity is greatly enhanced, by a factor of ∼14. Such an increase is mainly caused by the increment in the driving force. The droplet velocity changes nonlinearly as the surface wettability is varied and assumes the maximum at the contact angle of ∼75°. We derive a formula for the driving force of nanodroplets on general axisymmetric surfaces by evaluating the pressure gradient inside the droplet induced by the curvature gradient. Molecular dynamics simulations are performed to directly measure the driving force and confirm that the theoretical formula works well. By illustrating the reduced initial velocity of droplets as a function of a dimensionless number, which represents the ratio of the driving force to the retentive force due to contact angle hysteresis, we show that the onset of droplet motion on axisymmetric surfaces occurs when the dimensionless number is above a critical value. The dimensionless number reveals the effects of surface geometry, surface wettability, and droplet size on the droplet motion.

Surface Charge Density Inside a Silicon Nitride Nanopore.

Surface charges inside a nanopore determine the zeta potential and ion distributions and play a significant role in affecting ion transport and the sensitivity of detecting biomolecules. It is of great importance to study the fluctuation of surface charges with the salt concentration and pH in various applications of nanopores. Herein, we proposed a theoretical model to predict the surface charge density of a Si3N4 nanopore, in which both silanol and amine groups were taken into account. It was demonstrated that the surface charge density in the Si3N4 nanopore changes not only with pH but also with the salt concentration. The theoretical model could well predict the experimental results with different salt concentrations, pH values, and pore sizes. The effect of surface functional groups on the isopotential point (pHiep) of the Si3N4 nanopore was also systematically studied. The results indicated that the silanol groups are major determinants of the surface charge, but the influences of the amine groups should not be ignored because the small number of amine groups can change pHiep dramatically. The pHiep value of the Si3N4 nanopore was measured as 4.1, and the ratio of amine over silanol was ascertained as 0.013.

Modulating thermal conductance across the metal/graphene/SiO2 interface with ion irradiation.

Optimizing the efficiency of heat dissipation across an interface is a great challenge with the continuously increasing integration of microelectronic devices. In this work, an effective method in tuning the heat conduction across the Al/graphene/SiO2 interface is reported. It was found that the interfacial thermal conductance of Al/irradiated graphene/SiO2 can be increased by a factor of 3, as compared with that of Al/pristine graphene/SiO2. The X-ray photoelectron spectroscopy (XPS) analysis indicates that ion irradiation may promote the formation of CO bonds on the irradiated graphene surface, which is beneficial to the enhancement of interfacial thermal conductance. The density functional theory (DFT) calculations reveal that in addition to the formed bonds between O atoms and Al atoms, the adsorption strength between Al and irradiated graphene is intensified, which plays a dominant role in enhancing the interfacial thermal conductance of Al/graphene/SiO2.

Ion Concentration Effect on Nanoscale Electrospray Modes.

The phenomena and mechanism of electrospray modes in nanoscale are investigated from experiments and molecular dynamics simulations. It is found that the ionic concentration plays a crucial role in determining the dripping or the jetting modes in a nanoscale electrospray system. Molecular dynamics simulations uncover that the two modes are caused by the competition between the electric field stress and surface tension, which is similar to the mechanism in a macroscale electrospray system. However, in a nanoscale electrospray system, the two competing forces of the electric field stress and surface tension are more sensitive to the ion distributions than that in a macroscale electrospray system, in which the applied voltage and pressure dominate. With the decrease of the nozzle diameter to nanoscale, the ions not only affect the local electric field stress, but also destroy the hydrogen bonds among water molecules, which lead to that the ion concentration becomes a dominant factor in determining the electrospray modes in nanoscale. The discovery provides a novel method to control nanoscale electrospray modes, which may find potential applications for mass spectrometry, film deposition, and electrohydrodynamic printing.

Concentration effects on capture rate and translocation configuration of nanopore-based DNA detection.

Nanopore is a kind of powerful tool to detect single molecules and investigate fundamental biological processes. In biological cells or real detection systems, concentration of DNA molecules is various. Here, we report an experimental study of the effects of DNA concentration on capture rate and translocation configuration with different sized nanopores and applied voltages. Three classes of DNA translocation configurations have been observed including linear translocation, folded translocation, and cotranslocation. In the case of relatively large sized nanopore or high applied voltage, considerable cotranslocation events have been detected. The percentage of cotranslocation events also increases with DNA concentration, which leads to the relationship between capture rate and DNA concentration deviates from linearity. Therefore, in order to reflect the number of translocation molecules accurately, the capture rate should be corrected by double-counting cotranslocation events. These results will provide a valuable reference for the design of nanopore sensors.

Shape characterization and discrimination of single nanoparticles using solid-state nanopores.

Resistive pulse sensing with nanopores is expected to enable identification and analysis of nanoscale objects in ionic solutions. However, there is currently no remarkable method to characterize the three-dimensional shape of charged biomolecules or nanoparticles with low-cost and high-throughput. Here we demonstrate the sensing capability of solid-state nanopores for shape characterization of single nanoparticles by monitoring the ionic current blockades during their electrophoretic translocation through nanopores. By using nanopores that are a bit larger than the particles, shape characterization of both spherical and cubic silver nanoparticles is successfully realized due to their rapid rotation with respect to the pore axis, which is further validated by our all-atom molecular dynamics simulations. The single-molecule approach based on nanopores will allow people to measure the dimension and to characterize the shape of single nanoparticles or proteins simultaneously in real time, which is significant for its potential application in investigation of structural biology and proteomics in the near future.

Anisotropic thermoelectric effect and field-effect devices in epitaxial bismuthene on Si (111).

This experimental study reveals intriguing thermoelectric effects and devices in epitaxial bismuthene, two-dimensional (2D) bismuth with thickness ⩽30 nm, on Si (111). Bismuthene exhibits interesting anisotropic Seebeck coefficients varying 2-5 times along different crystal orientations, implying the existence of a puckered atomic structure like black phosphorus. An absolute value of Seebeck coefficient up to 237 µV K-1 sets a record for elemental Bi ever measured to the best of our knowledge. Electrical conductivity of bismuthene can reach up to 4.6 × 104 S m-1, which is sensitive to thickness and magnetic field. Along with a desired low thermal conductivity ∼1.97 W m-1 K that is 20% of its bulk form, the first experimental zT value at room temperature for bismuthene was measured ∼10-2, which is much higher than many other VA Xenes and comparable to its bulk compounds. Above results suggest a mixed buckled and puckered Bi atomic structure for epitaxial 2D bismuth on Si (111). Our work paves the way to explore potential applications, such as heat flux sensor, energy converting devices and so on for bismuthene.

Drastically Reduced Ion Mobility in a Nanopore Due to Enhanced Pairing and Collisions between Dehydrated Ions.

Ion transport through nanopores is a process of fundamental significance in nature and in engineering practice. Over the past decade, it has been found that the ion conductivity in nanopores could be drastically enhanced, and different mechanisms have been proposed to explain this observation. To date, most reported studies have been carried out with relatively dilute electrolytes, while ion transport in nanopores under high electrolyte concentrations (>1 M) has been rarely explored. Through systematic experimental and atomistic simulation studies with NaCl solutions, here we show that at high electrolyte concentrations, ion mobility in small nanopores could be significantly reduced from the corresponding bulk value. Subsequent molecular dynamics studies indicate that in addition to the low mobility of surface-bound ions in the Stern layer, enhanced pairing and collisions between partially dehydrated ions of opposite charges also make important contributions to the reduced ion mobility. Furthermore, we show that the extent of mobility reduction depends on the association constant between cations and anions in different electrolytes with a more drastic reduction for a larger association constant.