Sequence-Dependent Single-Molecule DNA Sensing Using Covalent Organic Framework Nanopores.

Enzyme-free single-molecule sequencing has the potential to significantly expand the application of nanopore technology to DNA, proteins, and saccharides. Despite their advantages over biological nanopores and natural suitability for enzyme-free single-molecule sequencing, conventional solid-state nanopores have not yet achieved single-molecule DNA sequencing. The biggest challenge for the accuracy of single-molecule sequencing using solid-state nanopores lies in the precise control of the pore size and conformity. In this study, we fabricated nanopore devices by covering the tip of a quartz nanopipette with ultrathin two-dimensional (2D) covalent organic framework (COF) nanosheets (pore size ≈ 1.1 nm). The size of the periodically arranged nanopores in COF is comparable to that of protein nanopores, and the structure of each COF nanopore is consistent at the atomic scale. The COF nanopore device could roughly distinguish dAMP, dCMP, dGMP, and dTMP. Furthermore, a certain percentage of the current blockades originating from 150 nucleotides model DNA molecules (13.5% for dA50dC50dA50 and 11.1% for dC50dA50dC50) show distinct DNA sequence-specific concave and convex resistive current patterns. The finite element simulation confirmed that the current blockade pattern of a DNA molecule passing through a COF nanopore is dependent on the relative location of the nanopore with respect to the wall of the nanopipette. Our study is a significant step toward single-molecule DNA sequencing by solid-state nanopores.

Closed Bipolar Nanoelectrode Array for Ultra-Sensitive Detection of Alkaline Phosphatase and Two-Dimensional Imaging of Epidermal Growth Factor Receptors.

The combination of closed bipolar electrodes (cBPE) with electrochemiluminescence (ECL) imaging has demonstrated remarkable capabilities in the field of bioanalysis. Here, we established a cBPE-ECL platform for ultrasensitive detection of alkaline phosphatase (ALP) and two-dimensional imaging of epidermal growth factor receptor (EGFR). This cBPE-ECL system consists of a high-density gold nanowire array in anodic aluminum oxide (AAO) membrane as the cBPE coupled with ECL of highly luminescent cadmium selenide quantum dots (CdSe QDs) luminophores to achieve cathodic electro-optical conversion. When an enzyme-catalyzed amplification effect of ALP with 4-aminophenyl phosphate monosodium salt hydrate (p-APP) as the substrate and 4-aminophenol (p-AP) as the electroactive probe is introduced, a significant improvement of sensing sensitivity with a detection limit as low as 0.5 fM for ALP on the cBPE-ECL platform can be obtained. In addition, the cBPE-ECL sensing system can also be used to detect cancer cells with an impressive detection limit of 50 cells/mL by labeling ALP onto the EGFR protein on A431 human epidermal cancer cell membranes. Thus, two-dimensional (2D) imaging of the EGFR proteins on the cell surface can be achieved, demonstrating that the established cBPE-ECL sensing system is of high resolution for spatiotemporal cell imaging.

High-Throughput Single-Molecule Surface-Enhanced Raman Spectroscopic Profiling of Single-Amino Acid Substitutions in Peptides by a Gold Plasmonic Nanopore.

Simultaneous detection and structural characterization of protein variants on a single platform are highly desirable but technically challenging. Herein, we present a single-molecule spectral system based on a gold plasmonic nanopore for analyzing two peptides and their single-point mutated variants. The gold plasmonic nanopore enabled the high-throughput acquisition of surface-enhanced Raman scattering (SERS) spectra at the single-molecule level by electrically driving analytes into hot spots. Furthermore, a statistical method based on Boolean operations was developed to extract prominent features from fluctuated single-molecule SERS spectra. The effects of the single-amino acid substitutions on both the intramolecular interactions and the peptide conformations were directly characterized by the nanopore system, and the results agreed with the predictions by AlphaFold2. This study highlights the mutual benefits of spectroscopy and nanopore technology, whereby the gold plasmonic nanopore offers a powerful tool for the structural analysis of single-molecule proteins.

Nanometer-Resolved Mapping of Organic Cation Migration Behavior in Methylammonium Lead Halide Perovskites.

The performance and stability of organic metal halide perovskite (OMHP) optoelectronic devices have been associated with ion migration. Understanding of nanoscale resolved organic cation migration mechanism would facilitate structure engineering and commercialization of OMHP. Here, we report a three-dimensional approach for in situ nanoscale infrared imaging of organic ion migration behavior in OMHPs, enabling to distinguish migrations along grain boundary and in crystal lattice. Our results reveal that organic cation migration along OMHP film surface and grain boundaries (GBs) occurs at lower biases than in crystal lattice. We visualize the transition of organic cation migration channels from GBs to volume upon increasing electric field. The temporal resolved results demonstrate the fast MA+ migration kinetics at GBs, which is comparable to diffusivity of halide ions. Our findings help understand the role of organic cations in the performance of OMHP devices, and the proposed approach holds broad applicability for revealing migration mechanisms of organic ions in OMHPs based optoelectronic devices.

Surface-phonon-polariton-enhanced photoinduced dipole force for nanoscale infrared imaging.

The photoinduced dipole force (PiDF) is an attractive force arising from the Coulombic interaction between the light-induced dipoles on the illuminated tip and the sample. It shows extreme sample-tip distance and refractive index dependence, which is promising for nanoscale infrared (IR) imaging of ultrathin samples. However, the existence of PiDF in the mid-IR region has not been experimentally demonstrated due to the coexistence of photoinduced thermal force (PiTF), typically one to two orders of magnitude higher than PiDF. In this study, we demonstrate that, with the assistance of surface phonon polaritons, the PiDF of c-quartz can be enhanced to surpass its PiTF, enabling a clear observation of PiDF spectra reflecting the properties of the real part of permittivity. Leveraging the detection of the PiDF of phonon polaritonic substrate, we propose a strategy to enhance the sensitivity and contrast of photoinduced force responses in transmission images, facilitating the precise differentiation of the heterogeneous distribution of ultrathin samples.

Synergistic Al-Al Dual-Atomic Site for Efficient Artificial Nitrogen Fixation.

Synthesis of ammonia by electrochemical nitrogen reduction reaction (NRR) is a promising alternative to the Haber-Bosch process. However, it is commonly obstructed by the high activation energy. Here, we report the design and synthesis of an Al-Al bonded dual atomic catalyst stabilized within an amorphous nitrogen-doped porous carbon matrix (Al2NC) with high NRR performance. The dual atomic Al2-sites act synergistically to catalyze the complex multiple steps of NRR through adsorption and activation, enhancing the proton-coupled electron transfer. This Al2NC catalyst exhibits a high Faradaic efficiency of 16.56±0.3 % with a yield rate of 29.22±1.2 µg h-1 mgcat -1. The dual atomic Al2NC catalyst shows long-term repeatable, and stable NRR performance. This work presents an insight into the identification of synergistic dual atomic catalytic site and mechanistic pathway for the electrochemical conversion of N2 to NH3.

Single-Molecule Discrimination of Saccharides Using Carbon Nitride Nanopores.

Structural complexity brings a huge challenge to the analysis of sugar chains. As a single-molecule sensor, nanopores have the potential to provide fingerprint information on saccharides. Traditionally, direct single-molecule saccharide detection with nanopores is hampered by their small size and weak affinity. Here, a carbon nitride nanopore device is developed to discern two types of trisaccharide molecules (LeApN and SLeCpN) with minor structural differences. The resolution of LeApN and SLeCpN in the mixture reaches 0.98, which has never been achieved in solid-state nanopores so far. Monosaccharide (GlcNAcpN) and disaccharide (LacNAcpN) can also be discriminated using this system, indicating that the versatile carbon nitride nanopores possess a monosaccharide-level resolution. This study demonstrates that the carbon nitride nanopores have the potential for conducting structure analysis on single-molecule saccharides.

Regulating ion affinity and dehydration of metal-organic framework sub-nanochannels for high-precision ion separation.

Membrane consisting of ordered sub-nanochannels has been pursued in ion separation technology to achieve applications including desalination, environment management, and energy conversion. However, high-precision ion separation has not yet been achieved owing to the lack of deep understanding of ion transport mechanism in confined environments. Biological ion channels can conduct ions with ultrahigh permeability and selectivity, which is inseparable from the important role of channel size and "ion-channel" interaction. Here, inspired by the biological systems, we report the high-precision separation of monovalent and divalent cations in functionalized metal-organic framework (MOF) membranes (UiO-66-(X)2, X = NH2, SH, OH and OCH3). We find that the functional group (X) and size of the MOF sub-nanochannel synergistically regulate the ion binding affinity and dehydration process, which is the key in enlarging the transport activation energy difference between target and interference ions to improve the separation performance. The K+/Mg2+ selectivity of the UiO-66-(OCH3)2 membrane reaches as high as 1567.8. This work provides a gateway to the understanding of ion transport mechanism and development of high-precision ion separation membranes.

Molecular architectures of iron complexes for oxygen reduction catalysis-Activity enhancement by hydroxide ions coupling.

Developing cost-effective and high-performance electrocatalysts for oxygen reduction reaction (ORR) is critical for clean energy generation. Here, we propose an approach to the synthesis of iron phthalocyanine nanotubes (FePc NTs) as a highly active and selective electrocatalyst for ORR. The performance is significantly superior to FePc in randomly aggregated and molecularly dispersed states, as well as the commercial Pt/C catalyst. When FePc NTs are anchored on graphene, the resulting architecture shifts the ORR potentials above the redox potentials of Fe2+/3+ sites. This does not obey the redox-mediated mechanism operative on conventional FePc with a Fe2+-N moiety serving as the active sites. Pourbaix analysis shows that the redox of Fe2+/3+ sites couples with HO- ions transfer, forming a HO-Fe3+-N moiety serving as the ORR active sites under the turnover condition. The chemisorption of ORR intermediates is appropriately weakened on the HO-Fe3+-N moiety compared to the Fe2+-N state and thus is intrinsically more ORR active.

Ultrasensitive Plasmon-Enhanced Infrared Spectroelectrochemistry.

IR spectroelectrochemistry (EC-IR) is a cutting-edge operando method for exploring electrochemical reaction mechanisms. However, detection of interfacial molecules is challenged by the limited sensitivity of existing EC-IR platforms due to the lack of high-enhancement substrates. Here, we propose an innovative plasmon-enhanced infrared spectroelectrochemistry (EC-PEIRS) platform to overcome this sensitivity limitation. Plasmonic antennae with ultrahigh IR signal enhancement are electrically connected via monolayer graphene while preserving optical path integrity, serving as both the electrode and IR substrate. The [Fe(CN)6 ]3- /[Fe(CN)6 ]4- redox reaction and electrochemical CO2 reduction reaction (CO2 RR) are investigated on the EC-PEIRS platform with a remarkable signal enhancement. Notably, the enhanced IR signals enable a reconstruction of the electrochemical curve of the redox reactions and unveil the CO2 RR mechanism. This study presents a promising technique for boosting the in-depth understanding of interfacial events across diverse applications.

Atomic Force Microscopy-Based Nanoscale Infrared Techniques for Catalysis.

Atomic force microscopy (AFM)-based nanoscale infrared (nano-IR) techniques have found extensive application in the fields of chemistry, physics, and materials science, enabling the visualization of nanoscale features that surpass the optical diffraction limit. More recently, tentative investigations have been conducted into the use of these techniques in the field of catalysis, particularly in studying interfacial processes involving molecular monolayer samples. IR nanoimaging and nanospectroscopy offer unique perspectives on catalytic processes. Considering the specific characteristics of catalytic processes, this Perspective highlights the need for and reviews the current status of AFM-based nano-IR techniques for catalysis investigations, which aims to contribute to a deeper understanding of the nanoscale mechanisms underlying the catalytic processes.

Unveiling the Solvent Effect in Plasmon Enhanced Electrochemistry via the Nanoparticle-Impact Technique.

Plasmon-enhanced electrochemistry (PEEC) has been observed to facilitate energy conversion systems by converting light energy to chemical energy. However, comprehensively understanding the PEEC mechanism remains challenging due to the predominant use of ensemble-based methodologies on macroscopic electrodes, which fails to measure electron-transfer kinetics due to constraints from mass transport and the averaging effect. In this study, we have employed nanoparticle impact electrochemistry (NIE), a newly developed electroanalytical technique capable of measuring electrochemical dynamics at a single-nanoparticle level under optimal mass transport conditions, along with microscopic electron-transfer theory for data interpretation. By investigating the plasmon enhanced hydrogen evolution reaction (HER) at individual silver nanoparticles (AgNPs), we have clearly revealed the previously unknown influence of solvent effects within the PEEC mechanism. This finding suggests an additional approach to optimize plasmon-assisted electrocatalysis and electrosynthesis systems.

Core-Shell Reactor Partitioning Enzyme and Prodrug by ZIF-8 for NADPH-Sensitive In Situ Prodrug Activation.

Enzyme-prodrug therapies have shown unique advantages in efficiency, selectivity, and specificity of in vivo prodrug activation. However, precise spatiotemporal control of both the enzyme and its substrate at the target site, preservation of enzyme activity, and in situ substrate depletion due to low prodrug delivery efficiency continue to be great challenges. Here, we propose a novel core-shell reactor partitioning enzyme and prodrug by ZIF-8, which integrates an enzyme with its substrate and increases the drug loading capacity (DLC) using a prodrug as the building ligand to form a Zn-prodrug shell. Cytochrome P450 (CYP450) is immobilized in ZIF-8, and the antitumor drug dacarbazine (DTIC) is coordinated and deposited in its outer layer with a high DLC of 43.6±0.8 %. With this configuration, a much higher prodrug conversion efficiency of CYP450 (36.5±1.5 %) and lower IC50 value (26.3±2.6 µg/mL) are measured for B16-F10 cells with a higher NADPH concentration than those of L02 cells and HUVECs. With the tumor targeting ability of hyaluronic acid, this core-shell enzyme reactor shows a high tumor suppression rate of 96.6±1.9 % and provides a simple and versatile strategy for enabling in vivo biocatalysis to be more efficient, selective, and safer.

Integrated separation and detection of exosomes via a label-free magnetic SERS platform.

A label-free magnetic surface enhanced Raman scattering (SERS) platform was constructed, which was composed of superparamagnetic Fe3O4 nanoparticles as cores for separation and Au layers as shells for label-free SERS detection. Our method could effectively distinguish exosomes from different cell sources for cancer diagnosis and showed high sensitivity and specificity within a 95% confidence interval. As a low-cost and efficient exosome analysis method, the designed integrated platform for separation and detection has promising applicability in clinical diagnostics.

Photoenhanced Electrocatalytic Hydrogen Evolution Accelerated Dominantly by the Hot Electrons from Intraband Transition rather than Interband Transition.

Plasmonic materials enabling sunlight as an energy input to catalyze the hydrogen evolution reaction (HER) have become the research focus of artificial photosynthesis. Upon visible photoexcitation, there are both intraband transition and interband transition hot carriers generated, and which of them dominates the catalytic reaction remains elusive. Here, the contributions of hot electrons from intraband and interband transitions to the photoelectrocatalytic HER on plasmonic Au triangle nanoprisms (AuTNPs) have been studied. Compared with the dark reaction, the exchange current density increases by 9-fold and 3-fold under intraband and interband excitation, respectively, which is attributed to the higher energy level of intraband transition hot electrons. By calculation of the reaction activation energy with and without illumination, the contributions of the hot electrons from the two photoexcitation modes to the photoenhanced electroreduction reaction (PEER) are quantitatively analyzed, proposing the general standard to measure the effect of different hot electrons in different reactions.

Ammonia-Induced Anomalous Ion Transport in Covalent Organic Framework Nanochannels.

More anomalous transport behaviors have been observed with the rapid progress in nanofabrication technology and characterization tools. The ions/molecules inside nanochannels can act dramatically different from those in the bulk systems and exhibit novel mechanisms. Here, we have reported the fabrication of a nanodevice, covalent organic frameworks covered theta pipette (CTP), that combine the advantages of theta pipette (TP), nanochannels framework, and field-effect transistors (FETs) for controlling and modulating the anomalous transport. Our results show that ammonia, a weak base, causes a continuous supply of ions inside covalent organic framework (COF) nanochannels, leading to an abnormally high current depending on the ionic/molecular size and the pore size of the nanochannel. Furthermore, CTP can distinguish different concentrations of ammonia and have all of the qualities of a nanosensor.

Janus Metal-Organic Framework Membranes Boosting the Osmotic Energy Harvesting.

The unique ion-transport properties in nanoconfined pores enable nanofluidic devices with great potential in harvesting osmotic energy. The energy conversion performance could be significantly improved by the precise regulation of the "permeability-selectivity" trade-off and the ion concentration polarization effect. Here, we take the advantage of electrodeposition technique to fabricate a Janus metal-organic framework (J-MOF) membrane that possesses rapid ion-transport capability and impeccable ion selectivity. The asymmetric structure and asymmetric surface charge distribution of the J-MOF device can suppress the ion concentration polarization effect and enhance the ion charge separation, exhibiting an improved energy harvesting performance. An output power density of 3.44 W/m2 has been achieved with the J-MOF membrane at a 1000-fold concentration gradient. This work provides a new strategy for fabricating high-performance energy-harvesting devices.