Ultrahigh-gain organic transistors based on van der Waals metal-barrier interlayer-semiconductor junction.

Intrinsic gain is a vital figure of merit in transistors, closely related to signal amplification, operation voltage, power consumption, and circuit simplification. However, organic thin-film transistors (OTFTs) targeted at high gain have suffered from challenges such as narrow subthreshold operating voltage, low-quality interface, and uncontrollable barrier. Here, we report a van der Waals metal-barrier interlayer-semiconductor junction-based OTFT, which shows ultrahigh performance including ultrahigh gain of ~104, low saturation voltage, negligible hysteresis, and good stability. The high-quality van der Waals-contacted junctions are mainly attributed to patterning EGaIn liquid metal electrodes by low-energy microfluidic processes. The wide-bandgap semiconductor Ga2O3 as barrier interlayer is achieved by in situ surface oxidation of EGaIn electrodes, allowing for an adjustable barrier height and expected thermionic emission properties. The organic inverters with a high gain of 5130 and a simplified current stabilizer are further demonstrated, paving a way for high-gain and low-power organic electronics.

Confined Nanopipet as a Versatile Tool for Precise Single Cell Manipulation.

The precise manipulation of single cells plays a fundamental role for single cell measurement, which is crucial for understanding the diverse cellular mechanisms. Unusual single cell behavior could thus be identified by integrating with advanced analytical methods such as single cell omics, unraveling the intrinsic cellular heterogeneity hidden in ensemble measurements. Herein, this technical note reports a nanopipet-based versatile method for manipulation of an ultrasmall volume of liquid, which further enables the precise manipulation of single cells. Femtoliter volumes of cytoplasm were extracted from single living cells and analyzed by time-of-flight secondary ion mass spectrometry. Moreover, several kinds of exogenous components were injected simultaneously into a cell, offering a delicate tool for multi-imaging in single living cells.

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

In this study, we designed SiNX 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 12.3 nm SiNX nanopore confined space decreased from 102 s-1 to 23 s-1, and the life-time of nanobubbles increased from 1.16 ms to 4.78 ms. The results further gave the activation energy for nanobubble nucleation which was 8.1 × 10-20 J with a 12.3 nm SiNX nanopore. Our method provides an efficient analytical tool for revealing the temperature-dependent nanobubble nucleation, which further benefits the fundamental understanding of nanobubble nucleation.

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 SiNX 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 NaBH4 and H2 O and as an ultra-sensitive sensor for monitoring the H2 nanobubble nucleation process. By carrying out the NaBH4 concentration-dependent experiments, we found the life-time of nanobubbles decreased 250 times and the frequency of nanobubble generation increased 38 times with the NaBH4 concentration increasing from 6 to 100 mM. The long-time equilibrium between gas molecules inward flux and outward flux could prolong the life-time of nanobubbles to hundreds of milliseconds at low NaBH4 concentration. The raw current trace depicted that the transient accumulation and dissolution of cavity occurred during all the life-time of nanobubbles. Therefore, the sub-9 nm SiNX nanopore shows a strong ability for real-time monitoring the nanobubble nucleation at early-stage with high temporal and spatial resolution. This work provides a guide to study the dynamic and stochastic characteristics of nanobubbles.

Wireless nanopore electrodes for analysis of single entities.

Measurements of a single entity underpin knowledge of the heterogeneity and stochastics in the behavior of molecules, nanoparticles, and cells. Electrochemistry provides a direct and fast method to analyze single entities as it probes electron/charge-transfer processes. However, a highly reproducible electrochemical-sensing nanointerface is often hard to fabricate because of a lack of control of the fabrication processes at the nanoscale. In comparison with conventional micro/nanoelectrodes with a metal wire inside, we present a general and easily implemented protocol that describes how to fabricate and use a wireless nanopore electrode (WNE). Nanoscale metal deposition occurs at the tip of the nanopipette, providing an electroactive sensing interface. The WNEs utilize a dynamic ionic flow instead of a metal wire to sense the interfacial redox process. WNEs provide a highly controllable interface with a 30- to 200-nm diameter. This protocol presents the construction and characterization of two types of WNEs-the open-type WNE and closed-type WNE-which can be used to achieve reproducible electrochemical measurements of single entities. Combined with the related signal amplification mechanisms, we also describe how WNEs can be used to detect single redox molecules/ions, analyze the metabolism of single cells, and discriminate single nanoparticles in a mixture. This protocol is broadly applicable to studies of living cells, nanomaterials, and sensors at the single-entity level. The total time required to complete the protocol is ~10-18 h. Each WNE costs ~$1-$3.

Characterization of the Dynamic Growth of the Nanobubble within the Confined Glass Nanopore.

The evolution of the nanobubble from gas molecules in liquid phase is of fundamental interest. However, the lack of sensitive tools hinders the study of growth dynamic of the bubble at nanoscale. Here, we employed a confined glass nanopore to real-time monitor the dynamics behavior of a single nanobubble generated by the reaction between NaBH4 and H2O. By analyzing the characteristic ionic current signal, the formation time and growth time of a single nanobubble could be estimated as 200 and 21 ms, respectively. Further, the nanopore size has been altered to modulate the growth behavior of the nanobubble. The results demonstrate the capability of the nanopore for sensitively tracking the behavior of single nanobubbles in liquid phase, which provides a powerful method for further understanding nanobubble evolution.

Manipulating and visualizing the dynamic aggregation-induced emission within a confined quartz nanopore.

Aggregation-induced emission (AIE) as a unique photophysical process has been intensively explored for their features in fields from optical sensing, bioimaging to optoelectronic devices. However, all AIE luminogens (AIEgens) hardly recover into the initial dispersed state after illuminating at the ultimate aggregated state, which limits AIEgens to achieve reversible sensing and reproducible devices. To real-time manipulate the emission of AIEgen, here we take the advantage of confined space in the quartz nanopore to achieve a nanopore-size-dependent restriction of AIEgens for reversible conversions of "on-to-off" and "off-to-on" emission. By electrochemically manipulating 26 fL AIEgen solution inside nanopore confinement, AIE illuminates while moves along nanopore from the constricted tip to inside cavity at a velocity of 1.4-2.2 µm s-1, and vice versa. We further apply this dynamic manipulation for a target delivery of AIEgen into single cells, which opens up new possibility to design powerful and practical AIE applications.

Asymmetric Nanopore Electrode-Based Amplification for Electron Transfer Imaging in Live Cells.

Capturing real-time electron transfer, enzyme activity, molecular dynamics, and biochemical messengers in living cells is essential for understanding the signaling pathways and cellular communications. However, there is no generalizable method for characterizing a broad range of redox-active species in a single living cell at the resolution of cellular compartments. Although nanoelectrodes have been applied in the intracellular detection of redox-active species, the fabrication of nanoelectrodes to maximize the signal-to-noise ratio of the probe remains challenging because of the stringent requirements of 3D fabrication. Here, we report an asymmetric nanopore electrode-based amplification mechanism for the real-time monitoring of NADH in a living cell. We used a two-step 3D fabrication process to develop a modified asymmetric nanopore electrode with a diameter down to 90 nm, which allowed for the detection of redox metabolism in living cells. Taking advantage of the asymmetric geometry, the above 90% potential drop at the two terminals of the nanopore electrode converts the faradaic current response into an easily distinguishable bubble-induced transient ionic current pattern. Therefore, the current signal was amplified by at least 3 orders of magnitude, which was dynamically linked to the presence of trace redox-active species. Compared to traditional wire electrodes, this wireless asymmetric nanopore electrode exhibits a high signal-to-noise ratio by increasing the current resolution from nanoamperes to picoamperes. The asymmetric nanopore electrode achieves the highly sensitive and selective probing of NADH concentrations as low as 1 pM. Moreover, it enables the real-time nanopore monitoring of the respiration chain (i.e., NADH) in a living cell and the evaluation of the effects of anticancer drugs in an MCF-7 cell. We believe that this integrated wireless asymmetric nanopore electrode provides promising building blocks for the future imaging of electron transfer dynamics in live cells.

A 30 nm Nanopore Electrode: Facile Fabrication and Direct Insights into the Intrinsic Feature of Single Nanoparticle Collisions.

Clarifying the hidden but intrinsic feature of single nanoparticles by nanoelectrochemistry could help understand its potential for diverse applications. The uncontrolled interface and bandwidth limitation in the electrochemical measurement put the obstacle in single particle collision. Here, we demonstrate a well-defined 30 nm nanopore electrode with a rapid chemical-electrochemical fabrication method which provides a high reproducibility in both size and performance. A capacitance-based detection mechanism is demonstrated to achieve a high current resolution of 0.6 pA ±0.1 pA (RMS) and a high the temporal resolution of 0.01 ms. By utilizing this electrode, the dynamic interactions of every single particle in the mixture could be directly read during the collision process. The collision frequency is two orders of magnitude higher than previous reports, which helps reveal the hidden features of nanoparticles during the complex and multidimensional interaction processes.

Label-Free Monitoring of Single Molecule Immunoreaction with a Nanopipette.

The nanopipette has been employed for the single molecule analysis due to its advantage of easy fabrication and controllable diameter. Herein, we present that the single molecule immunoreaction could be monitored by using the quartz nanopipette through the discrimination of characteristic blockade current, which reflect the intrinsic character of the individual unlabeled protein molecules due to its heterogeneous motion in solution. Our methods show the ability to monitor the immunoreaction between single α-fetal protein (AFP) and its specific antibody in aqueous solution without any labeling. Our studies may open a new door to comprehensively understand the single molecule immunoreaction, which gain more insight into the molecular dynamic of elementary steps.

Single antibody-antigen interactions monitored via transient ionic current recording using nanopore sensors.

Understanding the single molecular protein-protein interaction has great significance in evaluating the affinity of a specific antibody. Herein, the interaction between single α-fetal protein (AFP) and its antibody was monitored via transient ionic current recording by using the antibody functionalized nanopore sensors. More importantly, the kinetic evaluation was performed at the single molecule level to determine the dissociation constant of this interaction. This method enables the monitoring of the kinetic antigen-antibody interaction in their heterogenetic state without any labelling. Our results provided new insights into the evaluation of the antibody's binding affinity and more into the development of immunoassays for diagnostics.

Wireless Bipolar Nanopore Electrode for Single Small Molecule Detection.

Solid-state nanopore-based techniques have become a promising strategy for diverse single molecule detections. Owing to the challenge in well and rapid fabrication of solid-state nanopores with the diameter less than 2 nm, small molecule detection is hard to be addressed by existing label-free nanopore methods. In this work, we for the first time propose a metal-coated wireless nanopore electrode (WNE) which offers a novel and generally accessible detection method for analyzing small molecules and ions at the single molecule/ion level. Here, a silver-coated WNE is developed as a proof-of-principle model which achieves the detection the self-generated H2, the smallest known molecule, and Ag+ at single molecule/ion level by monitoring the enhanced ionic signatures. Under a bias potential of -800 mV, the WNE could accomplish the distinction of as low as 14 H2 molecules and 28 Ag+ from one spike signal. The finite element simulation is introduced to suggest that the generation of H2 at the orifice of the WNE results in the enhanced spike of ionic current. As a proof-of-concept experiment, the WNE is further utilized to directly detect Hg2+ from 100 pM to 100 nM by monitoring the frequency of the spike signals. This novel nanoelectrode provides a brand new label-free, ultrasensitive, and simple detection mechanism for various small molecules/ions detection, especially for redox analytes.

Dynamic Self-Assembly of Homogenous Microcyclic Structures Controlled by a Silver-Coated Nanopore.

The self-assembly of nanoparticles is a challenging process for organizing precise structures with complicated and ingenious structures. In the past decades, a simple, high-efficiency, and reproducible self-assembly method from nanoscale to microscale has been pursued because of the promising and extensive application prospects in bioanalysis, catalysis, photonics, and energy storage. However, microscale self-assembly still faces big challenges including improving the stability and homogeneity as well as pursuing new assembly methods and templates for the uniform self-assembly. To address these obstacles, here, a novel silver-coated nanopore is developed which serves as a template for electrochemically generating microcyclic structures of gold nanoparticles at micrometers with highly homogenous size and remarkable reproducibility. Nanopore-induced microcyclic structures are further applied to visualize the diffusion profile of ionic flux. Based on this novel strategy, a nanopore could potentially facilitate the delivery of assembled structures for many practical applications including drug delivery, cellular detection, catalysis, and plasmonic sensing.

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.

Single molecule study of initial structural features on the amyloidosis process.

We employed an α-hemolysin (α-HL) nanopore as a single-molecule tool to investigate the effects of initial structure on the amyloidosis process. The differences in the initial structure of two ß-amyloid (Aß) peptides (Aß25-35 and Aß35-25) could be distinguished in real-time due to their characteristic blockades. More importantly, the distinct aggregate dynamics for these two kinds of Aß fragments can be readily analyzed by monitoring the blockade frequency over time.