In Situ Oxygen Generation via a Platinum-Based Wireless Nanopore Electrode for Single-Cell Manipulation.

Oxygen production within human cells plays a critical role in cellular metabolism and is implicated in various diseases, including cancer. Investigating cellular heterogeneity under oxygen stimulation is crucial for elucidating disease mechanisms and advancing early therapeutic design. In this study, the platinum-based wireless nanopore electrode (WNE) with a diameter of ≈200 nm is employed as a powerful tool to produce oxygen molecules near the cell nucleus.

Wireless electrical-molecular quantum signalling for cancer cell apoptosis.

Quantum biological tunnelling for electron transfer is involved in controlling essential functions for life such as cellular respiration and homoeostasis. Understanding and controlling the quantum effects in biology has the potential to modulate biological functions. Here we merge wireless nano-electrochemical tools with cancer cells for control over electron transfer to trigger cancer cell death.

Simultaneous observation of the spatial and temporal dynamics of single enzymatic catalysis using a solid-state nanopore.

We developed a bipolar SiNx nanopore for the observation of single-molecule heterogeneous enzymatic dynamics. Single glucose oxidase was immobilized inside the nanopore and its electrocatalytic behaviour was real-time monitored continuous recording of ionic flux amplification. The temporal heterogeneity in enzymatic properties and its spatial dynamic orientations were observed simultaneously, and these two properties were found to be closely correlated.

3D Blockage Mapping for Identifying Familial Point Mutations in Single Amyloid-β Peptides with a Nanopore.

Accurate discrimination of amyloid-β (Aβ) peptides containing familial point mutations would advance the knowledge of their roles in early-onset Alzheimer's disease. Herein, we simultaneously identified the mutant A21G, E22G, E22Q, and the wild-type (WT) Aβ peptides with aerolysin nanopore using a 3D blockage mapping strategy. The standard deviation of current blockade fluctuations (σ ) was proposed as a new supplement to current blockage (I /I ) and duration time (t ) to profile the blockage characteristics of single molecules.

An advanced optical-electrochemical nanopore measurement system for single-molecule analysis.

Nanopore measurement has advanced in single-molecule analysis by providing a transient time and confined space window that only allows one interested molecule to exist. By optimization and integration of the electrical and optical analysis strategies in this transient window, the acquisition of comprehensive information could be achieved to resolve the intrinsic properties and heterogeneity of a single molecule. In this work, we present a roadmap to build a unified optical and electrochemical synchronous measurement platform for the research of a single molecule.

Revisiting the Origin of Nanopore Current Blockage for Volume Difference Sensing at the Atomic Level.

Changes in the nanopore ionic current during entry of a target molecule underlie the sensing capability and dominate the intensity and extent of applications of the nanopore approach. The volume exclusion model has been proposed and corrected to describe the nanopore current blockage. However, increasing evidence shows nonconformity with this model, suggesting that the ionic current within a nanopore should be entirely reconsidered.

Snapshotting the transient conformations and tracing the multiple pathways of single peptide folding using a solid-state nanopore.

A fundamental question relating to protein folding/unfolding is the time evolution of the folding of a protein into its precisely defined native structure. The proper identification of transition conformations is essential for accurately describing the dynamic protein folding/unfolding pathways. Owing to the rapid transitions and sub-nm conformation differences involved, the acquisition of the transient conformations and dynamics of proteins is difficult due to limited instrumental resolution.

Measuring temperature effects on nanobubble nucleation via a solid-state nanopore.

In this study, we designed SiN solid-state nanopores to detect the temperature effect on the hydrogen nanobubble formation. Here, we integrated a temperature controller with the highly sensitive nanopore. As the temperature decreases from 25 °C to 5 °C, the occurrence of the nanobubble nucleation inside a 12.

Monitoring nanobubble nucleation at early-stage within a sub-9 nm solid-state nanopore.

Nanobubble nucleation study is important for understanding the dynamic behavior of nanobubble growth, which is instructive for the nanobubble applications. Benefiting from nanopore fabrication, herein, we fabricated a sub-9 nm SiN nanopore with the comparable size to nanobubbles at early-stage. The confined nanopore interface serves as a generator for producing nanobubbles by the chemical reaction between NaBH and H O and as an ultra-sensitive sensor for monitoring the H nanobubble nucleation process.

Detection of structured single-strand DNA via solid-state nanopore.

Nanopore is a single-molecule analysis method which also employed electrophoresis has achieved promising single-molecule detections. In this study, we designed two kinds of confined spaces by fabricating solid-state nanopores with desirable diameters to study the structured single-strand DNA of C-rich quadruplex. For the nanopore whose diameter is larger than the quadruplex size, the DNA molecule could directly translocate through the nanopore with extremely high speed.

Detection of Single Proteins with a General Nanopore Sensor.

Single protein sensing based on solid-state nanopores is promising but challenging, because the fast translocation velocity of a protein is beyond the bandwidth of nanopore instruments. To decelerate the translocation speed, here, we employed a common protein cross-link interaction to achieve a general and robust nanopore sensing platform for single-molecule detection of protein. Benefiting from the EDC/NHS coupling interaction between nanopore and proteins, a 10-fold decrease in speed has been achieved.

A lithium-ion-active aerolysin nanopore for effectively trapping long single-stranded DNA.

Wild-type aerolysin (AeL) nanopores allow direct single nucleotide discrimination of very short oligonucleotides (≤10 nt) without labelling, which shows great potential for DNA sensing. To achieve real applications, one major obstacle of AeL is its poor capture ability of long single-stranded DNA (ssDNA, >10 nt). Here, we have proposed a novel and robust strategy for the electrostatic focusing of long ssDNA into a lithium-chloride (LiCl)-active AeL.

Dynamics of a Molecular Plug Docked onto a Solid-State Nanopore.

Docking of a protein-DNA complex onto a nanopore can provide ample observation time, and has enabled collection of analytic applications of biological nanopores, including DNA sequencing. However, the application of the same principle to solid-state nanopores is tempered by poor understanding of the docking process. Here, we elucidate the behavior of individual protein-DNA complexes docked onto a solid-state nanopore by monitoring the nanopore ionic current.

Measuring a frequency spectrum for single-molecule interactions with a confined nanopore.

Nanopore analysis is a powerful technique for single molecule analysis by virtue of its electrochemically confined effects. As a single molecule translocates through the nanopore, the featured ionic current pattern on the time scale contains single molecule characteristics including volume, charge, and conformational properties. Although the characteristics of a single molecule in a nanopore have been written to the featured ionic current, extracting the dynamic information from a complex current trace is still a big challenge.

In situ and real-time ToF-SIMS analysis of light-induced chemical changes in perovskite CHNHPbI.

A hybrid light/ToF-SIMS system was used to analyze the dynamic chemical changes of perovskite CH3NH3PbI3 films under light illumination, in order to reveal the mechanism of light instability for perovskite materials. Real-time material degradation and quasi-reversible iodine migration were successfully observed.

Direct sensing of cancer biomarkers in clinical samples with a designed nanopore.

Here, we show a designed solid-state nanopore sensor for the direct sensing and quantification of prostate-specific antigen (PSA) as cancer biomarker in serum without any pretreatment. This nanopore technique provides a convenient, fast, and low-cost quantification of cancer biomarkers in clinical samples.

Structural stability of the photo-responsive DNA duplexes containing one azobenzene via a confined pore.

Herein, the structural stability of single azobenzene modified DNA duplexes, including the trans form and cis form, has been examined separately based on their distinguishable unzipping kinetics from the mixture by an α-hemolysin nanopore. Furthermore, the accurate isomerization efficiency between the trans and cis form was obtained with single molecule resolution.

Characterization of DNA duplex unzipping through a sub-2 nm solid-state nanopore.

Herein, the unzipping and translocation of DNA duplexes through a sub-2 nm silicon nitride (SiN) solid-state nanopore have been demonstrated by well-resolved three-level blockades. In order to examine our observations, we applied a simple model which is applicable to the unzipping and translocation processes of DNA duplexes through solid-state nanopores. The generation of these highly recognizable signatures is an important step towards the real applications of solid-state nanopores in complex samples.

A precise pointing nanopipette for single-cell imaging via electroosmotic injection.

The precise transportation of fluorescent probes to the designated location in living cells is still a challenge. Here, we present a new addition to nanopipettes as a powerful tool to deliver fluorescent molecules to a given place in a single cell by electroosmotic flow, indicating favorable potential for further application in single-cell imaging.