Efficacy, safety, and immunogenicity of an inactivated, adjuvanted enterovirus 71 vaccine in infants and children: a multiregion, double-blind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Children are susceptible to severe or fatal enterovirus 71 (EV71) infections. We aimed to evaluate the efficacy, safety, and immunogenicity of EV71vac, an aluminium phosphate-adjuvanted inactivated EV71 vaccine in children aged 2-71 months. METHODS: We did a randomised, double-blinded, placebo-controlled, phase 3 trial at five hospitals in Taiwan and two in Vietnam. Children aged 2-71 months were stratified by country and age, and randomly assigned (1:1) to receive two doses of EV71vac or placebo via intramuscular injection 56 days apart. Children aged 2-23 months received a third booster dose on day 366. The primary endpoint was the clinical efficacy of the total vaccinated cohort against EV71-associated diseases during the follow-up period, from 14 days after the second dose to when 15 cases of EV71 infections were confirmed in the per-protocol population. Our safety analysis included all participants who received at least one dose of EV71vac. This trial is registered with ClinicalTrials.gov, NCT03865238, and is complete. FINDINGS: Between April 23 and Dec 25, 2019, of 3663 children assessed, 3061 were randomly assigned, of whom 3049 were vaccinated: 1521 children in the EV71vac group and 1528 in the placebo group. By May 20, 2021, our primary efficacy analysis included 2959 children, with 1476 children in the EV71vac group and 1483 children in the placebo group. The vaccine efficacy of EV71vac was 96·8% (95% CI 85·5-100) against EV71 associated diseases (p<0·0001). The percentage of participants who reported solicited adverse events were similar in both groups: 865 (56·9%) in the EV71vac group and 852 (55·8%) in the placebo group. Almost all reported solicited adverse events were mild and self-limited. INTERPRETATION: EV71vac is safe, well-tolerated, and highly effective in preventing EV71 associated diseases in children aged 2-71 months. FUNDING: Medigen Vaccine Biologics and A+ Industrial Innovative R&D Program of the Ministry of Economic Affairs, Taiwan.

Decelerated Hot Carrier Cooling in Graphene via Nondissipative Carrier Injection from MoS2.

One key to improve the performance of advanced optoelectronic devices and energy harvesting in graphene is to understand the predominant carrier scattering via optical phonons. Nevertheless, low light absorbance in graphene yields a limited photoexcited carrier density, hampering the hot carrier effect, which is strongly correlated to the hot optical phonon bottleneck effect as the energy-loss channel. Here, by integrating graphene with monolayer MoS2 possessing stronger light absorbance, we demonstrate an efficient interfacial hot carrier transfer between graphene and MoS2 in their heterostructure with a prolonged relaxation time using broadband transient differential transmittance spectroscopy. We observe that the carrier relaxation time of graphene in the heterostructure is 4 times slower than that of bare graphene. This is explained by nondissipative interlayer transfer from MoS2 to graphene, which is attributed to the enhanced hot optical phonon bottleneck effect of graphene in the heterostructure by an increased photoexcited carrier population. A significant reduction of both amplitude and relaxation time in A- and B-excitons is another evidence of the interlayer transfer from MoS2 to graphene. The nondissipative interlayer charge transfer from MoS2 to graphene is confirmed by density functional calculations. This provides a different platform to further study the photoinduced hot carrier effect in graphene heterostructures for photothermoelectric detectors or hot carrier solar cells.

Layer-controlled single-crystalline graphene film with stacking order via Cu-Si alloy formation.

Multilayer graphene and its stacking order provide both fundamentally intriguing properties and technological engineering applications. Several approaches to control the stacking order have been demonstrated, but a method of precisely controlling the number of layers with desired stacking sequences is still lacking. Here, we propose an approach for controlling the layer thickness and crystallographic stacking sequence of multilayer graphene films at the wafer scale via Cu-Si alloy formation using direct chemical vapour deposition. C atoms are introduced by tuning the ultra-low-limit CH4 concentration to form a SiC layer, reaching one to four graphene layers at the wafer scale after Si sublimation. The crystallographic structure of single-crystalline or uniformly oriented bilayer (AB), trilayer (ABA) and tetralayer (ABCA) graphene are determined via nano-angle-resolved photoemission spectroscopy, which agrees with theoretical calculations, Raman spectroscopy and transport measurements. The present study takes a step towards the layer-controlled growth of graphite and other two-dimensional materials.

Coherent Thermoelectric Power from Graphene Quantum Dots.

The quantum confinement of charge carriers has been a promising approach to enhance the efficiency of thermoelectric devices, by lowering the dimension of materials and raising the boundary phonon scattering rate. The role of quantum confinement in thermoelectric efficiency has been investigated by using macroscopic device-scale measurements based on diffusive electron transport with the thermal de Broglie wavelength of the electrons. Here, we report a new class of thermoelectric operation originating from quasi-bound state electrons in low-dimensional materials. Coherent thermoelectric power from confined charges was observed at room temperature in graphene quantum dots with diameters of several nanometers. The graphene quantum dots, electrostatically defined as circular n-p-n junctions to isolate charges in the p-type graphene quantum dots, enabled thermoelectric microscopy at the atomic scale, revealing weakly localized and coherent thermoelectric power generation. The conceptual thermoelectric operation provides new insights, selectively enhancing coherent thermoelectric power via resonant states of charge carriers in low-dimensional materials.

Retraction Note: Large local lattice expansion in graphene adlayers grown on copper.

The authors unanimously wish to retract this Article due to their concerns about the interpretation of the low-energy electron microscopy (LEEM) and diffraction (LEED) patterns reported in the manuscript. In this study, the authors used spatial and angle-resolved photoemission spectroscopy (ARPES) to characterize graphene monolayers grown on copper foils, and observed regions of graphene adlayers with enhanced graphene/Cu interaction, higher Dirac cone doping level, moiré mini Dirac cones and large lattice expansion. All these properties have been clearly verified and reproduced by photoemission spectroscopy as well as explained by density functional theory. LEEM and LEED characterization were also carried out to confirm the existence of a moiré superlattice and lattice expansion, and the results were included in the main manuscript and Supplementary Information. On further analysis of the LEEM/LEED data, it seems that while the existence of a moiré superlattice can be corroborated, the conclusion of graphene lattice expansion (7%) based on spatially resolved ARPES determinations cannot be confirmed by the LEEM/LEED measurements. The authors realized that these measurements were collected from statistically non-representative areas of the sample. Moreover, the fact that the raw microLEED images bear an asymmetry factor of as much as 5% due to the instrumental aberration makes it impossible to estimate any compression or expansion of the same order. Consequently, their conclusion on the graphene lattice expansion can only be supported by the photoemission data. In view that more complete and reliable structural determinations should be conducted, all authors wish to retract this Article.

Large local lattice expansion in graphene adlayers grown on copper.

Variations of the lattice parameter can significantly change the properties of a material, and, in particular, its electronic behaviour. In the case of graphene, however, variations of the lattice constant with respect to graphite have been limited to less than 2.5% due to its well-established high in-plane stiffness. Here, through systematic electronic and lattice structure studies, we report regions where the lattice constant of graphene monolayers grown on copper by chemical vapour deposition increases up to ~7.5% of its relaxed value. Density functional theory calculations confirm that this expanded phase is energetically metastable and driven by the enhanced interaction between the substrate and the graphene adlayer. We also prove that this phase possesses distinctive chemical and electronic properties. The inherent phase complexity of graphene grown on copper foils revealed in this study may inspire the investigation of possible metastable phases in other seemingly simple heterostructure systems.

Ultrafast Spectral Photoresponse of Bilayer Graphene: Optical Pump-Terahertz Probe Spectroscopy.

Photoinduced terahertz conductivity Δσ(ω) of Bernal stacked bilayer graphene (BLG) with different dopings is measured by time-resolved optical pump terahertz probe spectroscopy. The real part of photoconductivity Δσ(ω) (ΔσRe(ω)) is positive throughout the spectral range 0.5-2.5 THz in low-doped BLG. This is in sharp contrast to Δσ(ω) for high-doped bilayer graphene where ΔσRe(ω) is negative at low frequency and positive on the high frequency side. We use Boltzmann transport theory to understand quantitatively the frequency dependence of Δσ(ω), demanding the energy dependence of different scattering rates such as short-range impurity scattering, Coulomb scattering, carrier-acoustic phonon scattering, and substrate surface optical phonon scattering. We find that the short-range disorder scattering dominates over other processes. The calculated photoconductivity captures very well the experimental conductivity spectra as a function of lattice temperature varying from 300 to 4 K, without any empirical fitting procedures adopted so far in the literature. This helps us to understand the intraband conductivity of photoexcited hot carriers in 2D materials.

Transient Carrier Cooling Enhanced by Grain Boundaries in Graphene Monolayer.

Using a high terahertz (THz) electric field (ETHz), the carrier scattering in graphene was studied with an electric field of up to 282 kV/cm. When the grain size of graphene monolayers varies from small (5 µm) and medium (70 µm) to large grains (500 µm), the dominant carrier scattering source in large- and small-grained graphene differs at high THz field, i.e., there is optical phonon scattering for large grains and defect scattering for small grains. Although the electron-optical phonon coupling strength is the same for all grain sizes in our study, the enhanced optical phonon scattering in the high THz field from the large-grained graphene is caused by a higher optical phonon temperature, originating from the slow relaxation of accelerated electrons. Unlike the large-grained graphene, lower electron and optical phonon temperatures are found in the small-grained graphene monolayer, resulting from the effective carrier cooling through the defects, called supercollisions. Our results indicate that the carrier mobility in the high-crystalline graphene is easily vulnerable to scattering by the optical phonons. Thus, controlling the population of defect sites, as a means for carrier cooling, can enhance the carrier mobility at high electric fields in graphene electronics by suppressing the heating of optical phonons.

A High-On/Off-Ratio Floating-Gate Memristor Array on a Flexible Substrate via CVD-Grown Large-Area 2D Layer Stacking.

Memristors such as phase-change memory and resistive memory have been proposed to emulate the synaptic activities in neuromorphic systems. However, the low reliability of these types of memories is their biggest challenge for commercialization. Here, a highly reliable memristor array using floating-gate memory operated by two terminals (source and drain) using van der Waals layered materials is demonstrated. Centimeter-scale samples (1.5 cm × 1.5 cm) of MoS2 as a channel and graphene as a trap layer grown by chemical vapor deposition (CVD) are used for array fabrication with Al2 O3 as the tunneling barrier. With regard to the memory characteristics, 93% of the devices exhibit an on/off ratio of over 103 with an average ratio of 104 . The high on/off ratio and reliable endurance in the devices allow stable 6-level memory applications. The devices also exhibit excellent memory durability over 8000 cycles with a negligible shift in the threshold voltage and on-current, which is a significant improvement over other types of memristors. In addition, the devices can be strained up to 1% by fabricating on a flexible substrate. This demonstration opens a practical route for next-generation electronics with CVD-grown van der Waals layered materials.

Tuning Carrier Tunneling in van der Waals Heterostructures for Ultrahigh Detectivity.

Semiconducting transition metal dichalcogenides (TMDs) are promising materials for photodetection over a wide range of visible wavelengths. Photodetection is generally realized via a phototransistor, photoconductor, p-n junction photovoltaic device, and thermoelectric device. The photodetectivity, which is a primary parameter in photodetector design, is often limited by either low photoresponsivity or a high dark current in TMDs materials. Here, we demonstrated a highly sensitive photodetector with a MoS2/h-BN/graphene heterostructure, by inserting a h-BN insulating layer between graphene electrode and MoS2 photoabsorber, the dark-carriers were highly suppressed by the large electron barrier (2.7 eV) at the graphene/h-BN junction while the photocarriers were effectively tunneled through small hole barrier (1.2 eV) at the MoS2/h-BN junction. With both high photocurrent/dark current ratio (>105) and high photoresponsivity (180 AW-1), ultrahigh photodetectivity of 2.6 × 1013 Jones was obtained at 7 nm thick h-BN, about 100-1000 times higher than that of previously reported MoS2-based devices.

Two-terminal floating-gate memory with van der Waals heterostructures for ultrahigh on/off ratio.

Concepts of non-volatile memory to replace conventional flash memory have suffered from low material reliability and high off-state current, and the use of a thick, rigid blocking oxide layer in flash memory further restricts vertical scale-up. Here, we report a two-terminal floating gate memory, tunnelling random access memory fabricated by a monolayer MoS2/h-BN/monolayer graphene vertical stack. Our device uses a two-terminal electrode for current flow in the MoS2 channel and simultaneously for charging and discharging the graphene floating gate through the h-BN tunnelling barrier. By effective charge tunnelling through crystalline h-BN layer and storing charges in graphene layer, our memory device demonstrates an ultimately low off-state current of 10(-14) A, leading to ultrahigh on/off ratio over 10(9), about ∼10(3) times higher than other two-terminal memories. Furthermore, the absence of thick, rigid blocking oxides enables high stretchability (>19%) which is useful for soft electronics.

Stranski-Krastanov and Volmer-Weber CVD Growth Regimes To Control the Stacking Order in Bilayer Graphene.

Aside from unusual properties of monolayer graphene, bilayer has been shown to have even more interesting physics, in particular allowing bandgap opening with dual gating for proper interlayer symmetry. Such properties, promising for device applications, ignited significant interest in understanding and controlling the growth of bilayer graphene. Here we systematically investigate a broad set of flow rates and relative gas ratio of CH4 to H2 in atmospheric pressure chemical vapor deposition of multilayered graphene. Two very different growth windows are identified. For relatively high CH4 to H2 ratios, graphene growth is relatively rapid with an initial first full layer forming in seconds upon which new graphene flakes nucleate then grow on top of the first layer. The stacking of these flakes versus the initial graphene layer is mostly turbostratic. This growth mode can be likened to Stranski-Krastanov growth. With relatively low CH4 to H2 ratios, growth rates are reduced due to a lower carbon supply rate. In addition bi-, tri-, and few-layer flakes form directly over the Cu substrate as individual islands. Etching studies show that in this growth mode subsequent layers form beneath the first layer presumably through carbon radical intercalation. This growth mode is similar to that found with Volmer-Weber growth and was shown to produce highly oriented AB-stacked materials. These systematic studies provide new insight into bilayer graphene formation and define the synthetic range where gapped bilayer graphene can be reliably produced.

Large-Scale Graphene on Hexagonal-BN Hall Elements: Prediction of Sensor Performance without Magnetic Field.

A graphene Hall element (GHE) is an optimal system for a magnetic sensor because of its perfect two-dimensional (2-D) structure, high carrier mobility, and widely tunable carrier concentration. Even though several proof-of-concept devices have been proposed, manufacturing them by mechanical exfoliation of 2-D material or electron-beam lithography is of limited feasibility. Here, we demonstrate a high quality GHE array having a graphene on hexagonal-BN (h-BN) heterostructure, fabricated by photolithography and large-area 2-D materials grown by chemical vapor deposition techniques. A superior performance of GHE was achieved with the help of a bottom h-BN layer, and showed a maximum current-normalized sensitivity of 1986 V/AT, a minimum magnetic resolution of 0.5 mG/Hz(0.5) at f = 300 Hz, and an effective dynamic range larger than 74 dB. Furthermore, on the basis of a thorough understanding of the shift of charge neutrality point depending on various parameters, an analytical model that predicts the magnetic sensor operation of a GHE from its transconductance data without magnetic field is proposed, simplifying the evaluation of each GHE design. These results demonstrate the feasibility of this highly performing graphene device using large-scale manufacturing-friendly fabrication methods.

Wafer-Scale Single-Crystalline AB-Stacked Bilayer Graphene.

Single-crystalline artificial AB-stacked bilayer graphene is formed by aligned transfer of two single-crystalline monolayers on a wafer-scale. The obtained bilayer has a well-defined interface and is electronically equivalent to exfoliated or direct-grown AB-stacked bilayers.

Selective Area Band Engineering of Graphene using Cobalt-Mediated Oxidation.

This study reports a scalable and economical method to open a band gap in single layer graphene by deposition of cobalt metal on its surface using physical vapor deposition in high vacuum. At low cobalt thickness, clusters form at impurity sites on the graphene without etching or damaging the graphene. When exposed to oxygen at room temperature, oxygen functional groups form in proportion to the cobalt thickness that modify the graphene band structure. Cobalt/Graphene resulting from this treatment can support a band gap of 0.30 eV, while remaining largely undamaged to preserve its structural and electrical properties. A mechanism of cobalt-mediated band opening is proposed as a two-step process starting with charge transfer from metal to graphene, followed by formation of oxides where cobalt has been deposited. Contributions from the formation of both CoO and oxygen functional groups on graphene affect the electronic structure to open a band gap. This study demonstrates that cobalt-mediated oxidation is a viable method to introduce a band gap into graphene at room temperature that could be applicable in electronics applications.

Monitoring defects on monolayer graphene using nematic liquid crystals.

Defects in graphene governs electrical and optical properties. Although grain boundaries in graphene inevitably formed during large area synthesis process, which act as scattering centers for charge carriers to degrade mobility, have been studied extensively, point defects have been rarely investigated mainly due to the absence of facile observation tools. Here, we report polarized optical microscopy to observe defect distributions in monolayer graphene. This was realized by aligning liquid crystal s (LC) on graphene where the defect population was modulated by irradiating ultraviolet (UV) light directly on graphene surface under moisture condition. Aromatic rings in LC molecules are oriented with hexagonal rings in graphene to have preferred orientation, providing a way to identify relative orientations of graphene domains and point defects. Our studies show that point defects generated by prolonged UV irradiation time give rise to irregular LC alignment with disclination lines on the graphene surface and a large-size LC domain associated with graphene single domain eventually disappeared. This indicates that defects associated with oxygen-containing functional groups cause to reduce the strong stacking interaction between graphene and LC molecules.

Towards Wafer-Scale Monocrystalline Graphene Growth and Characterization.

Since its discovery in 2004, graphene has boosted numerous fundamental sciences and technological applications due to its massless Dirac particle-like linear band dispersion, that causes unprecedented physical properties. Among the various methods for synthesizing graphene, chemical vapor deposition is the most suitable approach for scalable production on a wafer scale, which is a critical step for practical applications. Graphene grain boundaries (GGBs), consisting of nonhexagonal carbon rings and therefore modulating the properties of graphene films, are inevitably formed via the merging of adjacent graphene domains with different orientations. Large-area monocrystalline graphene synthesis without forming GGBs has been challenging, let alone observing such boundaries. Here, an up-to-date review is presented of how to grow wafer-scale monocrystalline graphene without GGBs. One approach is to make single domain sizes as large as possible by reducing or passivating the number of nucleation sites. Another approach is to align graphene domains in identical orientations, and then merge them atomically. The recently developed methods for observing graphene orientation and GGBs both at the atomic and macro-scales are also presented. Finally, perspectives for future research in graphene growth are discussed.

Seamless stitching of graphene domains on polished copper (111) foil.

Seamless stitching of graphene domains on polished copper (111) is proved clearly not only at atomic scale by scanning tunnelling microscopy (STM) and transmission electron micoscopy (TEM), but also at the macroscale by optical microscopy after UV-treatment. Using this concept of seamless stitching, synthesis of 6 cm × 3 cm monocrystalline graphene without grain boundaries on polished copper (111) foil is possible, which is only limited by the chamber size.

Charge transport in polycrystalline graphene: challenges and opportunities.

Graphene has attracted significant interest both for exploring fundamental science and for a wide range of technological applications. Chemical vapor deposition (CVD) is currently the only working approach to grow graphene at wafer scale, which is required for industrial applications. Unfortunately, CVD graphene is intrinsically polycrystalline, with pristine graphene grains stitched together by disordered grain boundaries, which can be either a blessing or a curse. On the one hand, grain boundaries are expected to degrade the electrical and mechanical properties of polycrystalline graphene, rendering the material undesirable for many applications. On the other hand, they exhibit an increased chemical reactivity, suggesting their potential application to sensing or as templates for synthesis of one-dimensional materials. Therefore, it is important to gain a deeper understanding of the structure and properties of graphene grain boundaries. Here, we review experimental progress on identification and electrical and chemical characterization of graphene grain boundaries. We use numerical simulations and transport measurements to demonstrate that electrical properties and chemical modification of graphene grain boundaries are strongly correlated. This not only provides guidelines for the improvement of graphene devices, but also opens a new research area of engineering graphene grain boundaries for highly sensitive electro-biochemical devices.