Extracellular Vesicles: A New Paradigm for Cellular Communication in Perioperative Medicine, Critical Care, and Pain Management.

Extracellular vesicles (EVs) play critical roles in many health and disease states, including ischemia, inflammation, and pain, which are major concerns in the perioperative period and in critically ill patients. EVs are functionally active, nanometer-sized, membrane-bound vesicles actively secreted by all cells. Cell signaling is essential to physiological and pathological processes, and EVs have recently emerged as key players in intercellular communication. Recent studies in EV biology have improved our mechanistic knowledge of the pathophysiological processes in perioperative and critical care patients. Studies also show promise in using EVs in novel diagnostic and therapeutic clinical applications. This review considers the current advances and gaps in knowledge of EVs in the areas of ischemia, inflammation, pain, and in organ systems that are most relevant to anesthesiology, perioperative medicine, critical care, and pain management. We expect the reader will better understand the relationship between EVs and perioperative and critical care pathophysiological states and their potential use as novel diagnostic and therapeutic modalities.

Controlling Photoluminescence Enhancement and Energy Transfer in WS2 :hBN:WS2 Vertical Stacks by Precise Interlayer Distances.

2D semiconducting transition metal dichalcogenides (TMDs) are endowed with fascinating optical properties especially in their monolayer limit. Insulating hBN films possessing customizable thickness can act as a separation barrier to dictate the interactions between TMDs. In this work, vertical layered heterostructures (VLHs) of WS2 :hBN:WS2 are fabricated utilizing chemical vapor deposition (CVD)-grown materials, and the optical performance is evaluated through photoluminescence (PL) spectroscopy. Apart from the prohibited indirect optical transition due to the insertion of hBN spacers, the variation in the doping level of WS2 drives energy transfer to arise from the layer with lower quantum efficiency to the other layer with higher quantum efficiency, whereby the total PL yield of the heterosystem is increased and the stack exhibits a higher PL intensity compared to the sum of those in the two WS2 constituents. Such doping effects originate from the interfaces that WS2 monolayers reside on and interact with. The electron density in the WS2 is also controlled and subsequent modulation of PL in the heterostructure is demonstrated by applying back-gated voltages. Other influential factors include the strain in WS2 and temperature. Being able to tune the energy transfer in the VLHs may expand the development of photonic applications in 2D systems.

Revealing Strain-Induced Effects in Ultrathin Heterostructures at the Nanoscale.

Two-dimensional materials are being increasingly studied, particularly for flexible and wearable technologies because of their inherent thickness and flexibility. Crucially, one aspect where our understanding is still limited is on the effect of mechanical strain, not on individual sheets of materials, but when stacked together as heterostructures in devices. In this paper, we demonstrate the use of Kelvin probe microscopy in capturing the influence of uniaxial tensile strain on the band-structures of graphene and WS2 (mono- and multilayered) based heterostructures at high resolution. We report a major advance in strain characterization tools through enabling a single-shot capture of strain defined changes in a heterogeneous system at the nanoscale, overcoming the limitations (materials, resolution, and substrate effects) of existing techniques such as optical spectroscopy. Using this technique, we observe that the work-functions of graphene and WS2 increase as a function of strain, which we attribute to the Fermi level lowering from increased p-doping. We also extract the nature of the interfacial heterojunctions and find that they get strongly modulated from strain. We observe that the strain-enhanced charge transfer with the substrate plays a dominant role, causing the heterostructures to behave differently from two-dimensional materials in their isolated forms.

Atomically thin optomemristive feedback neurons.

Cognitive functions such as learning in mammalian brains have been attributed to the presence of neuronal circuits with feed-forward and feedback topologies. Such networks have interactions within and between neurons that provide excitory and inhibitory modulation effects. In neuromorphic computing, neurons that combine and broadcast both excitory and inhibitory signals using one nanoscale device are still an elusive goal. Here we introduce a type-II, two-dimensional heterojunction-based optomemristive neuron, using a stack of MoS2, WS2 and graphene that demonstrates both of these effects via optoelectronic charge-trapping mechanisms. We show that such neurons provide a nonlinear and rectified integration of information, that can be optically broadcast. Such a neuron has applications in machine learning, particularly in winner-take-all networks. We then apply such networks to simulations to establish unsupervised competitive learning for data partitioning, as well as cooperative learning in solving combinatorial optimization problems.

Probing Carrier Dynamics in Large-Scale MBE-Grown PtSe2 Films by Terahertz Spectroscopy.

Atomically thin platinum diselenide (PtSe2) films are promising for applications in the fields of electronics, spintronics, and photodetectors owing to their tunable electronic structure and high carrier mobility. Using terahertz (THz) spectroscopy techniques, we investigated the layer-dependent semiconducting-to-metallic phase transition and associated intrinsic carrier dynamics in large-scale PtSe2 films grown by molecular beam epitaxy. The uniformity of large-scale PtSe2 films was characterized by spatially and frequency-resolved THz-based sheet conductivity mapping. Furthermore, we use an optical-pump-THz-probe technique to study the transport dynamics of photoexcited carriers and explore light-induced intergrain carrier transport in PtSe2 films. We demonstrate large-scale THz-based mapping of the electrical properties of transition metal dichalcogenide films and show that the two noncontact THz-based approaches provide insight in the spatial and temporal properties of PtSe2 films.

Large-Scale Uniform-Patterned Arrays of Ultrathin All-2D Vertical Stacked Photodetector Devices.

The key to unlocking the full potential of two-dimensional (2D) materials in ultrathin opto-electronics is their layer-by-layer integration and the ability to produce them on the wafer scale using traditional industry-compatible technology. Here, we demonstrate a novel stacking method for assembling uniform-patterned periodic 2D arrays into vertical-layered heterostructures. The fabricated heterostructure can serve as photodetectors, with graphene electrodes and transition-metal dichalcogenides as the photo-absorber. All 2D materials used are grown into continuous films with only mono- or bilayer thickness. Each layer is prepatterned into a specific shape on a substrate and then transferred to the device substrate with aligned precision. In order to achieve long-range alignment across the wafer, interlocking marker pairs are used to help guide the lateral accuracy and reduce rotational error. We show hundreds of identical devices produced with 2D periodic spacing on a 1 cm × 1 cm SiO2/Si substrate, a fundamental prerequisite for future pixelated detectors. Statistics of the photovoltaic performance of the devices are reported, with values that are comparable to devices made by chemical vapor deposition-grown materials. Our work provides pathways for the large-scale fabrication of ultrathin all-2D opto-electronics that form the basis of the future in 2D-pixelated cameras and displays.

Frequency, predictors, and prognosis of heart failure with improved left ventricular ejection fraction: a single-centre retrospective observational cohort study.

AIMS: An improved left ventricular ejection fraction (HFiEF) was observed across heart failure (HF) patients with a reduced or mid-range ejection fraction (HFrEF or HFmrEF, respectively). We postulated that HFiEF patients are clinically distinct from non-HFiEF patients. METHODS AND RESULTS: A total of 447 patients hospitalized due to a clinical diagnosis of HF (LVEF <50% at baseline) were enrolled from September 2017 to September 2019. Echocardiogram re-evaluation was conducted repeatedly over 6 months of follow-up after discharge. The primary endpoint included the composite of HF hospitalization and all-cause mortality. Subjects (n = 184) with HFiEF (defined as an absolute LVEF improvement≥10%) were compared with 263 non-HFiEF (defined by <10% improvement in LVEF) subjects. Multivariable Cox regression was performed and identified younger age, smaller left ventricular end diastolic dimension (LVEDD), beta-blocker use, AF ablation and cardiac resynchronization therapy (CRT) as independent predictors of HFiEF. According to Kaplan-Meier analysis, HFiEF subjects had lower cardiac composite outcomes (P = 0.002) and all-cause mortality (P = 0.003) than non-HFiEF subjects. Multivariate Cox survival analysis revealed that non-HFiEF (compared with HFiEF) was an independent predictor of both the primary endpoints (HR = 0.679, 95% CI: 0.451-0.907, P = 0.012), which was driven by all-cause mortality (HR = 0.504, 95% CI: 0.256-0.991, P = 0.047). CONCLUSIONS: These data confirm that compared with non-HFiEF, HFiEF is a distinct HF phenotype with favourable clinical outcomes.

Super-Resolution Nanolithography of Two-Dimensional Materials by Anisotropic Etching.

Nanostructuring allows altering of the electronic and photonic properties of two-dimensional (2D) materials. The efficiency, flexibility, and convenience of top-down lithography processes are, however, compromised by nanometer-scale edge roughness and resolution variability issues, which especially affect the performance of 2D materials. Here, we study how dry anisotropic etching of multilayer 2D materials with sulfur hexafluoride (SF6) may overcome some of these issues, showing results for hexagonal boron nitride (hBN), tungsten disulfide (WS2), tungsten diselenide (WSe2), molybdenum disulfide (MoS2), and molybdenum ditelluride (MoTe2). Scanning electron microscopy and transmission electron microscopy reveal that etching leads to anisotropic hexagonal features in the studied transition metal dichalcogenides, with the relative degree of anisotropy ranked as: WS2 > WSe2 > MoTe2 ∼ MoS2. Etched holes are terminated by zigzag edges while etched dots (protrusions) are terminated by armchair edges. This can be explained by Wulff constructions, taking the relative stabilities of the edges and the AA' stacking order into account. Patterns in WS2 are transferred to an underlying graphite layer, demonstrating a possible use for creating sub-10 nm features. In contrast, multilayer hBN exhibits no lateral anisotropy but shows consistent vertical etch angles, independent of crystal orientation. Using an hBN crystal as the base, ultrasharp corners can be created in lithographic patterns, which are then transferred to a graphite crystal underneath. We find that the anisotropic SF6 reactive ion etching process makes it possible to downsize nanostructures and obtain smooth edges, sharp corners, and feature sizes significantly below the resolution limit of electron beam lithography. The nanostructured 2D materials can be used themselves or as etch masks to pattern other nanomaterials.

High Photoresponsivity in Ultrathin 2D Lateral Graphene:WS2:Graphene Photodetectors Using Direct CVD Growth.

We show that reducing the degree of van der Waals overlapping in all 2D ultrathin lateral devices composed of graphene:WS2:graphene leads to significant increase in photodetector responsivity. This is achieved by directly growing WS2 using chemical vapor deposition (CVD) in prepatterned graphene gaps to create epitaxial interfaces. Direct-CVD-grown graphene:WS2:graphene lateral photodetecting transistors exhibit high photoresponsivities reaching 121 A/W under 2.7 × 105 mW/cm2 532 nm illumination, which is around 2 orders of magnitude higher than similar devices made by the layer-by-layer transfer method. The photoresponsivity of our direct-CVD-grown device shows negative correlation with illumination power under different gate voltages, which is different from similar devices made by the transfer method. We show that the high photoresponsivity is due to the lowering of effective Schottky barrier height by improving the contact between graphene and WS2. Furthermore, the direct CVD growth reduces overlapping sections of WS2:Gr and leads to more uniform lateral systems. This approach provides insights into scalable manufacturing of high-quality 2D lateral electronic and optoelectronic devices.

Grain Boundaries as Electrical Conduction Channels in Polycrystalline Monolayer WS2.

We show that grain boundaries (GBs) in polycrystalline monolayer WS2 can act as conduction channels with a lower gate onset potential for field-effect transistors made parallel, compared to devices made in pristine areas and perpendicular to GBs. Localized doping at the GB causes photoluminescence quenching and a reduced Schottky barrier with the metal electrodes, resulting in higher conductivity at lower applied bias values. Samples are grown by chemical vapor deposition with large domains of ∼100 µm, enabling numerous devices to be made within single domains, across GBs and at many similar sites across the substrate to reveal similar behaviors. We corroborate our electrical measurements with Kelvin probe microscopy, highlighting the nature of the doping-type in the material to change at the grain boundaries. Molecular dynamics simulations of the GB are used to predict the atomic structure of the dislocations and meandering tilt GB behavior on the nanoscale. These results show that GBs can be used to provide conduction pathways that are different to transport across GBs and in pristine area for potential electronic applications.

Symmetry-Controlled Reversible Photovoltaic Current Flow in Ultrathin All 2D Vertically Stacked Graphene/MoS2/WS2/Graphene Devices.

Atomically thin vertical heterostructures are promising candidates for optoelectronic applications, especially for flexible and transparent technologies. Here, we show how ultrathin all two-dimensional vertical-stacked type-II heterostructure devices can be assembled using only materials grown by chemical vapor deposition, with graphene (Gr) as top and bottom electrodes and MoS2/WS2 as the active semiconductor layers in the middle. Furthermore, we show that the stack symmetry, which dictates the type-II directionality, is the dominant factor in controlling the photocurrent direction upon light irradiation, whereas in homobilayers, photocurrent direction cannot be easily controlled because the tunnel barrier is determined by the doping levels of the graphene, which appears fixed for top and bottom graphene layers due to their dielectric environments. Therefore, the ability to direct photovoltaic current flow is demonstrated to be only possible using heterobilayers (HBs) and not homobilayers. We study the photovoltaic effects in more than 40 devices, which allows for statistical verification of performance and comparative behavior. The photovoltage in the graphene/transition-metal dichalcogenide-heterobilayer/graphene (Gr/TMD-HB (MoS2/WS2)/Gr) increases up to 10 times that generated in the monolayer TMD devices under the same optical illumination power, due to efficient charge transfer between WS2 and MoS2 and extraction to graphene electrodes. By applying external gate voltages ( Vg), the band alignment can be tuned, which in turn controls the photovoltaic effect in the vertical heterostructures. The tunneling-assisted interlayer charge recombination also plays a significant role in modulating the photovoltaic effect in the Gr/TMD-HB/Gr. These results provide important insights into how layer symmetry in vertical-stacked graphene/TMD/graphene ultrathin optoelectronics can be used to control electron flow directions during photoexcitation and open up opportunities for tandem cell assembly.

Photocurrent Direction Control and Increased Photovoltaic Effects in All-2D Ultrathin Vertical Heterostructures Using Asymmetric h-BN Tunneling Barriers.

Two-dimensional (2D) materials are atomically thick and without out-of-plane dangling bonds. As a result, they could break the confinement of lattice matching, and thus can be freely mixed and matched together to construct vertical van der Waals heterostructures. Here, we demonstrated an asymmetrical vertical structure of graphene/hexagonal boron nitride (h-BN)/tungsten disulfide (WS2)/graphene using all chemical vapor deposition grown 2D materials. Three building blocks are utilized in this construction: conductive graphene as a good alternative for the metal electrode due to its tunable Fermi level and ultrathin nature, semiconducting transition-metal dichalcogenides (TMDs) as an ultrathin photoactive material, and insulating h-BNas a tunneling barrier. Such an asymmetrical vertical structure exhibits a much stronger photovoltaic effect than the symmetrical vertical one without h-BN. By changing the sequence of h-BN in the vertical stack, we could even control the electron flow direction. Also, improvement has been further made by increasing the thickness of h-BN. The photovoltaic effect is attributed to different possibilities of excited electrons on TMDs to migrate to top and bottom graphene electrodes, which is caused by potential differences introduced by an insulating h-BN layer. This study shows that h-BN could be effectively used as a tunneling barrier in the asymmetrical vertical heterostructure to improve photovoltaic effect and control the electron flow direction, which is crucial for the design of other 2D vertical heterostructures to meet various needs of electronic and optoelectronic devices.

Hydrogen-Assisted Growth of Large-Area Continuous Films of MoS2 on Monolayer Graphene.

We show how control over the chemical vapor deposition (CVD) reaction chemistry of molybdenum disulfide (MoS2) by hydrogen addition can enable the direct growth of centimeter-scale continuous films of vertically stacked MoS2 monolayer on graphene under atmospheric pressure conditions. Hydrogen addition enables longer CVD growth times at high temperature by reducing oxidation effects that would otherwise degrade the monolayer graphene. By careful control of nucleation density and growth time, high-quality monolayer MoS2 films could be formed on graphene, realizing all CVD-grown vertically stacked monolayer semimetal/semiconducting interfaces. Photoluminescence spectroscopy shows quenching of MoS2 by the underlying graphene, indicating a good interfacial charge transfer. We utilize the MoS2/graphene vertical stacks as photodetectors, with photoresponsivities reaching 2.4 A/W under 135 µW 532 nm illumination. This approach provides insights into the scalable manufacturing of high-quality two-dimensional electronic and optoelectronic devices.

Utilizing Interlayer Excitons in Bilayer WS2 for Increased Photovoltaic Response in Ultrathin Graphene Vertical Cross-Bar Photodetecting Tunneling Transistors.

Here we study the layer-dependent photoconductivity in Gr/WS2/Gr vertical stacked tunneling (VST) cross-bar devices made using two-dimensional (2D) materials all grown by chemical vapor deposition. The larger number of devices (>100) enables a statistically robust analysis on the comparative differences in the photovoltaic response of monolayer and bilayer WS2, which cannot be achieved in small batch devices made using mechanically exfoliated materials. We show a dramatic increase in photovoltaic response for Gr/WS2(2L)/Gr compared to monolayers because of the long inter- and intralayer exciton lifetimes and the small exciton binding energy (both interlayer and intralayer excitons) of bilayer WS2 compared with that of monolayer WS2. Different doping levels and dielectric environments of top and bottom graphene electrodes result in a potential difference across a ∼1 nm vertical device, which gives rise to large electric fields perpendicular to the WS2 layers that cause band structure modification. Our results show how precise control over layer number in all 2D VST devices dictates the photophysics and performance for photosensing applications.

Chemical Vapor Deposition Growth of Two-Dimensional Monolayer Gallium Sulfide Crystals Using Hydrogen Reduction of Ga2S3.

Two-dimensional gallium sulfide (GaS) crystals are synthesized by a simple and efficient ambient pressure chemical vapor deposition (CVD) method using a single-source precursor of Ga2S3. The synthesized GaS structures involve triangular monolayer domains and multilayer flakes with thickness of 1 and 15 nm, respectively. Regions of continuous films of GaS are also achieved with about 0.7 cm2 uniform coverage. This is achieved by using hydrogen carrier gas and the horizontally placed SiO2/Si substrates. Electron microscopy and spectroscopic measurements are used to characteristic the CVD-grown materials. This provides important insights into novel approaches for enlarging the domain size of GaS crystals and understanding of the growth mechanism using this precursor system.

High-Performance All 2D-Layered Tin Disulfide: Graphene Photodetecting Transistors with Thickness-Controlled Interface Dynamics.

Tin disulfide crystals with layered two-dimensional (2D) sheets are grown by chemical vapor deposition using a novel precursor approach and integrated into all 2D transistors with graphene (Gr) electrodes. The Gr:SnS2:Gr transistors exhibit excellent photodetector response with high detectivity and photoresponsivity. We show that the response of the all 2D photodetectors depends upon charge trapping at the interface and the Schottky barrier modulation. The thickness-dependent SnS2 measurements in devices reveal a transition from the interface-dominated response for thin crystals to bulklike response for the thicker SnS2 crystals, showing the sensitivity of devices fabricated using layered materials on the number of layers. These results show that SnS2 has photosensing performance when combined with Gr electrodes that is comparable to other 2D transition metal dichalcogenides of MoS2 and WS2.

Electrical Breakdown of Suspended Mono- and Few-Layer Tungsten Disulfide via Sulfur Depletion Identified by in Situ Atomic Imaging.

The high-bias and breakdown behavior of suspended mono- and few-layer WS2 was explored by in situ aberration-corrected transmission electron microscopy. The suspended WS2 devices were found to undergo irreversible breakdown at sufficiently high biases due to vaporization of the WS2. Simultaneous to the removal of WS2 was the accompanying formation of few-layer graphene decorated with W and WS2 nanoparticles, with the carbon source attributed to organic residues present on the WS2 surface. The breakdown of few-layer WS2 resulted in the formation of faceted S-depleted WS2 tendrils along the vaporization boundary, which were found to exhibit lattice contraction indicative of S depletion, alongside pure W phases incorporated into the structure, with the interfaces imaged at atomic resolution. The combination of observing the graphitization of the amorphous carbon surface residue, W nanoparticles, and S-depleted WS2 phases following the high-bias WS2 disintegration all indicate a thermal Joule heating breakdown mechanism over an avalanche process, with WS2 destruction promoted by preferential S emission. The observation of graphene formation and the role the thin amorphous carbon layer has in the prebreakdown behavior of the device demonstrate the importance of employing encapsulated heterostructure device architectures that exclude residues.

Photoluminescence Segmentation within Individual Hexagonal Monolayer Tungsten Disulfide Domains Grown by Chemical Vapor Deposition.

We show that hexagonal domains of monolayer tungsten disulfide (WS2) grown by chemical vapor deposition (CVD) with powder precursors can have discrete segmentation in their photoluminescence (PL) emission intensity, forming symmetric patterns with alternating bright and dark regions. Two-dimensional maps of the PL reveal significant reduction within the segments associated with the longest sides of the hexagonal domains. Analysis of the PL spectra shows differences in the exciton to trion ratio, indicating variations in the exciton recombination dynamics. Monolayers of WS2 hexagonal islands transferred to new substrates still exhibit this PL segmentation, ruling out local strain in the regions as the dominant cause. High-power laser irradiation causes preferential degradation of the bright segments by sulfur removal, indicating the presence of a more defective region that is higher in oxidative reactivity. Atomic force microscopy (AFM) images of topography and amplitude modes show uniform thickness of the WS2 domains and no signs of segmentation. However, AFM phase maps do show the same segmentation of the domain as the PL maps and indicate that it is caused by some kind of structural difference that we could not clearly identify. These results provide important insights into the spatially varying properties of these CVD-grown transition metal dichalcogenide materials, which may be important for their effective implementation in fast photo sensors and optical switches.

Lateral Graphene-Contacted Vertically Stacked WS2 /MoS2 Hybrid Photodetectors with Large Gain.

A demonstration is presented of how significant improvements in all-2D photodetectors can be achieved by exploiting the type-II band alignment of vertically stacked WS2 /MoS2 semiconducting heterobilayers and finite density of states of graphene electrodes. The photoresponsivity of WS2 /MoS2 heterobilayer devices is increased by more than an order of magnitude compared to homobilayer devices and two orders of magnitude compared to monolayer devices of WS2 and MoS2 , reaching 103 A W-1 under an illumination power density of 1.7 × 102 mW cm-2 . The massive improvement in performance is due to the strong Coulomb interaction between WS2 and MoS2 layers. The efficient charge transfer at the WS2 /MoS2 heterointerface and long trapping time of photogenerated charges contribute to the observed large photoconductive gain of ≈3 × 104 . Laterally spaced graphene electrodes with vertically stacked 2D van der Waals heterostructures are employed for making high-performing ultrathin photodetectors.