We present the design of a concentric tube (CT) reactor for roll-to-roll chemical vapor deposition (CVD) on flexible substrates, and its application to continuous production of graphene on copper foil. In the CTCVD reactor, the thin foil substrate is helically wrapped around the inner tube, and translates through the gap between the concentric tubes. We use a bench-scale prototype machine to synthesize graphene on copper substrates at translation speeds varying from 25 mm/min to 500 mm/min, and investigate the influence of process parameters on the uniformity and coverage of graphene on a continuously moving foil. At lower speeds, high-quality monolayer graphene is formed; at higher speeds, rapid nucleation of small graphene domains is observed, yet coalescence is prevented by the limited residence time in the CTCVD system. We show that a smooth isothermal transition between the reducing and carbon-containing atmospheres, enabled by injection of the carbon feedstock via radial holes in the inner tube, is essential to high-quality roll-to-roll graphene CVD. We discuss how the foil quality and microstructure limit the uniformity of graphene over macroscopic dimensions. We conclude by discussing means of scaling and reconfiguring the CTCVD design based on general requirements for 2-D materials manufacturing. For thin films of graphene, such promising applications include transparent electrodes for displays and photovoltaics, high-performance filtration membranes, and thermal imagers1-D materi3456et al. produced uniform graphene films on 30" diagonal Cu foils that were wrapped around a 7.5” diameter quartz tube placed for static processing inside an 8” diameter quartz tube within a tube furnace. The graphene films were subsequently transferred to PET following a wet chemical etch of the Cuet al. to produce 40" diagonal films of graphene that were subsequently transferred to PETSeveral systems and methods for roll-to-roll (R2R) graphene production have been presented in the academic literature13141516e.g., as seen in carbon fiber production)1819e.g., integration with patterning operations)15e.g., temperature, pressure, atmosphere composition, feed rate, quality) similar to parametric studies performed for batch-scale graphene growth using static reactor conditions222324e.g., number of layers, domain size, quality) to meet both application-oriented needs and production specifications .Despite these achievements, it is still necessary to advance continuous production of 2D materials to reflect a rigorous understanding of the underlying process physics, and to enable high-quality layer-controlled production at a high rate. For graphene in particular, the design of the R2R CVD system is critical to establish such understanding, and design principles that should be captured in an effective system include: thermal and fluidic uniformity over the substrate; efficient mixing and use of the feedstock gases; sealed and controlled gas atmospheres and thermal zones , increased reactor temperature (from 1000 °C to 1045 °C), and a He/H2 cooling atmosphere give a 1.9x, 1.4x and 1.9x improvement of I2D/IG, respectively.We present a new reactor design for R2R CVD of 2-D materials on flexible substrates, and using a benchtop prototype of this reactor, we study R2R production of graphene on metal foils. The reactor has a concentric tube geometry, which achieves several desirable features for R2R CVD, including thermal and fluidic uniformity over the substrate due to the small gap, a rapid isothermal transition between the two internal atmospheres via the small gap between the tubes, and enable the size of the treatment zone to be adjusted without changing the flow profile over the substrate. The prototype CTCVD system is built using a standard tube furnace , and the end chambers contain web-handling mechanisms built largely using commercial-off-the-shelf components (In the concentric tube (CT) CVD reactor design , the submponents . The usevia the injection of the precursor gas through the inner tube. For example, a first gas mixture such as He/H2 is supplied to the upstream chamber, and flows into the gap between the tubes; and a second gas mixture including the precursor is directly fed to the inner tube. The inner tube is custom-made with radial holes and a blockage adjacent to the holes; these direct the second gas mixture to enter the annular gap, creating the second gas treatment zone without changing the local temperature profile. The flow dynamics in the CTCVD system with downstream injection were studied using computational fluid dynamics (CFD) simulations, at system pressures of 10–3 and 760 torr. The mixing of C2H4 upon injection from the inner tube is visualized in A further attractive feature of the CTCVD design is the ability to create two sequential treatment zones  via the Additionally, the design of the CTCVD system enables a seamless thermal gradient  across t22i.e., where the system was fully stopped and reloaded between tests) and a continuous run where the velocity was adjusted as the substrate was fed through the CTCVD reactor In both cases, graphene was grown on 60 cm of foil at each velocity. No statistically relevant differences in the graphene produced were found when comparing the two experimentation methods.Using the CTCVD system, we first chose to investigate the relationship between the process velocity and the characteristics of graphene produced on Cu foil (see Methods). Experiments were performed at translation speeds between 25 mm/min and 500 mm/min, under identical temperature and gas flow conditions (see Methods). We performed independent tests at each speed . A similar inverse relationship is observed between the IG/ID ratio and substrate velocity , which may indicate an increase in the number of graphene layers , or increasing edge defect density at higher substrate velocity25In ncreases , implyinvelocity , indicat2, samples processed at 25 mm/min show a clean spectrum consistent with high-quality monolayer graphene  exposures, and repeated interrogation of the same spots resulted in the same Raman spectrum as the first collection. Nevertheless, to avoid variation in results due to the transfer process itself, the following results are presented directly on the Cu substrate.After transfer to SiOgraphene . The SiOe.g., 2  mm/min), and isolated nanoscale graphene domains at high substrate velocities . This agrees with previous studies that found graphene growth begins by formation of nanoscale domains at nucleation sites on Cu, which can coalesce given sufficient time29High-resolution SEM imaging on Cu was also used to examine the uniformity of graphene coverage at different velocities . Judging2D/IG ratio is driven by edge defects rather than the number of graphene layers. In the case of uniform coverage, an increase in the number of graphene layers causes the 2D peak to broaden and shift to higher frequency. However, in the case of small graphene domains, the 2D peak is relatively much broader due to edge defects and orientation mismatches between domains. In the present study, as the translation speed increases and the coverage of graphene becomes less continuous, we observe that the 2D peak broadens and the peak intensity decreases. Incidentally, 2D peak broadening relative to graphene films has been observed in graphene quantum dots (GQDs) having diameters of 5–35 nm, where the 2D peak broadened as the number of edge defects and relative GQD orientation mismatch to neighboring GQDs increased2 , we attribute this to the polycrystalline nature of the Cu substrate, not the reactor design.We next assessed the graphene uniformity by comparing Raman spectra taken across the width and length of each sample . Additionally, a long (4 m) Cu substrate was translated through the reactor at a rate of 75 mm/min , and the Raman data is shown in Fig. S4b (see Supporting Information) for locations every 30 mm along the length of the foil. Although there is a significant variation in the IThe kinetics of graphene nucleation and growth will depend on the orientation and surface conditions of each Cu grain323334353637i.e., surface roughness, pits, indentations) as a result of the manufacturing process . This topography undoubtedly influences the uniformity and coverage of graphene by influencing the nucleation site density and presenting mechanical barriers to lateral growth. Comparison of the survey spectra  with the average spectra of several Raman scans conducted within individual Cu grains supports the theory that the variation seen across the length of the sample is due to the defects in the substrate surface and the polycrystalline nature of the substrate .In addition, the surface of the Cu foil had striations and mechanically formed defects  and ended downstream of the furnace had low quality graphene. Thus, we conclude that it is important to heat the Cu foil while exposing it to a non-carbon atmosphere, and to transition to the carbon atmosphere at elevated temperature. The benefit of downstream hydrocarbon injection is also illustrated in i.e., H2/C2H4 injected in the annular gap from the input of the system, no downstream holes) and two treatment zones . Downstream injection yields roughly 2.7x and 1.8x increases in I2D/IG and IG/ID respectively, relative to the single-zone design. The importance of an isothermal transition from a reducing atmosphere to a carbon-containing atmosphere was also highlighted in a recent study that used a diffusion barrier (Al2O3 on Ni) to prevent carbon exposure until the elevated temperature was reached in a single-zone systemTo isolate the influence of each zone of the reactor, experiments were performed by moving the Cu foil from selected points spanning from upstream to downstream of the heated region, resulting in the Raman spectra shown in 2 annealing at elevated temperature. At 25 mm/min, the exposure of the grain boundaries during the annealing of the Cu requires ~100 mm of travel (4 min residence time), and at ~125 mm (~25 mm upstream of the inner tube injection holes) we find that Cu grains begin to darken optically, and nanoscale graphene domains are found in the SEM images. This is also the first location along the length of the substrate that G, D and 2D peaks are observable on the Raman spectrum. As the foil progresses further through the reactor, maximum coverage of graphene is achieved between the 175 mm and 225 mm locations , representing 120–240 seconds of exposure beyond the nucleation point. Moreover, we find some Cu grains become nearly fully covered within less than 45 seconds (at the end of a 250 mm/min run), compared to the much longer time to achieve maximum coverage (120–240 seconds) on the polycrystalline foil . Improved crystallinity and surface conditions of the foil could therefore greatly increase the throughput and quality of the R2R CVD process.To further ascertain the substrate treatment kinetics within the CTCVD reactor, a Cu foil sample undergoing constant velocity processing was abruptly stopped and cooled rapidly by opening the furnace cover and applying a cold air stream across the reactor wall with a fan. Optical images and SEM images at marked locations on the substrate show the graphene coverage as a function of time in the reactor . Raman soC and then the carbon source was turned on in the growth zone, and translation motion was started for graphene growth. We compared speeds of 25 and 125 mm/min, at which we had previously observed full graphene coverage on most Cu grains, and disconnected nanoscale graphene domains, respectively in the baseline study. With the extended pre-annealing step, a significant increase in the graphene I2D/IG ratio to 1.39 was realized at 125 mm/min . Finally, previous studies have attributed the increase in the I2D/IG ratio after similar annealing treatment to Cu grain growthLast, we sought to identify principles for improved R2R production of graphene using the CTCVD system. It is understood that annealing prior to carbon exposure improves the viability of the Cu substrate for high-quality graphene growth by reducing surface oxides, healing surface defects on Cu, and by promoting Cu grain growth29305 mm/min , as comp of 0.74 . However2D/IG ratios . After 20 seconds of only He and H2 flowing in the reactor , the system was cooled according to the normal procedure. On the region that was cooled within the growth zone of the furnace while exposed only to He/H2 flow, we observed a moderate average increase in the I2D/IG ratio from 0.74 to 1.37  form in the CVD environment to 1.37 . As a rei.e. the annular region) of the CTCVD design is significantly less than a standard circular tube, feedstock gas consumption can be reduced by greater than 90% while for an equivalent average velocity. Efficient conversion and consumption of feedstock is essential from a cost and environmental standpoint when considering manufacturing at scale44Beyond the characteristics of graphene achieved in this study, the design principles embodied by the CTCVD system are important to establish high-rate, high-quality continuous manufacturing of graphene on metal foils. First, because the cross-sectional area , and graphene growth. The conditions for each zone can therefore be optimized, along with the foil characteristics, to achieve the desired coverage and uniformity of graphene on the foil. The relative residence time can be specified in each zone by the length of each zone and by the single helical pitch of the wrap. The observed inverse relationship between graphene coverage and process rate  suggests that improved graphene coverage at high rate can be achieved by increasing the furnace length. Further, the same downstream injection principle could be implemented for atmospheric pressure CVD processing, along with custom rectangular (flat) tubes that could have one or more substrates translating on each inner tube surface. Each of these characteristics enables the bench-top CTCVD system to be scaled for graphene production at high rate and quality.Second, graphene characteristics can be tuned Nevertheless, there will be practical limits to the process conditions that can be implemented. For example, the maximum temperature will be limited by carbon pyrolysis and softening of the Cu substrate (which causes it to stretch and break under tension below its melting temperature). Also, to establish a third distinct gas zone for cooling of the substrate, a third gas mixture could be injected upstream from the far end of the annular gap, and issued outward through the inner tube while reversing direction and rapidly combining with the hydrocarbon flow away from the substrate.Improvements in foil manufacturing and pre-treatment to reduce surface roughness and microstructure are also very important to improve the quality of the graphene produced. Also, for many applications where graphene must be transferred to a secondary substrate such as PET, it will be important to integrate continuous transfer and lamination methods13We also consider that the graphene growth process itself is what ultimately limits the production rate. Initial modeling of the heat transfer to the Cu foil in the CTCVD system predicts that the foil can be heated to 1000 °C within 10 mm of furnace entry, at a speed exceeding 5 m/min. Therefore, discovery of methods to improve graphene nucleation and growth kinetics will not be limited by the thermal mass of the foil, and in fact contact between the foil and the inner tube significantly increases the heating rate compared to a freestanding foil. Based on present results, individual grains become fully covered within a residence time equivalent to 250 mm/min, which to our knowledge is the fastest rate yet reported in academic literature on R2R graphene growth.e.g., in situ Raman spectroscopy) and real-time data analysis can help accelerate the identification of process conditions for improved and application-specific material characteristics. Wider availability of graphene in a continuous format will also be useful to advance transfer and patterning methods for 2-D device manufacturing.In summary, the CTCVD design presents a scalable and modular approach to continuous production of thin films such as graphene on flexible substrates. While roll-to-roll synthesis of high-quality graphene is achieved in this study, the greater value of this work lies in the understanding of the process parameter space along with challenges presented by the characteristics of the metal substrate. In future work, integration of online metrology  was rinsed and manually wiped using Kimwipes soaked with acetone, and then wiped with Kimwipes soaked in isopropyl alcohol. The foil was anchored to the supply roller and wrapped onto the roller, and then the roller was manually loaded into the supply chamber. The foil was then wrapped around the inner tube and fed from the supply roller such that the helical path around the inner tube consisted of 1.5 revolutions between the supply and take-up rollers. Upon reaching the take-up reel, the downstream end of the foil was adhered to the take-up reel, and the take-up reel was rotated/advanced 90° (translating the foil ~50 mm) to ensure free motion of the foil through the system.The desired length of 0.25" wide, 0.002" thick metal foil . The inner tube used for all experiments was a 13 mm OD (10 mm ID) quartz tube, resulting in a tube-tube annular gap of 4.5 mm. Gas flow control  was dictated by the user through a custom LabView control interface. Prior to loading the foil for each experiment, the system was baked at a furnace temperature of 875 °C with a 500 sccm flow of dry air for 30 min. This step removed carbon deposits from the inner tube surfaces and created a consistent baseline starting condition for each R2R experiment. Additionally, after loading the foil for each experiment, the system was evacuated to 2 Torr while flowing He to remove the air that was introduced during the installation of the substrate material. The furnace was then heated to 1010 °C and a pressure of 4 Torr, with flows of 100 sccm H2O) for 24 hours to etch the metal foil2 substrate was then carefully immersed in the solution and slowly removed such that the graphene was pinned to the SiO2 substrate by the meniscus during the substrate extraction. Following a rinse in deionized water, the sample was dried at 50 °C on a hot plate, in air, for 10 minutes.The backside of the Cu foil was wet sanded with emery paper to remove the graphene layer on that side. The sample was then floated, graphene face up, in an aqueous solution of iron nitrate (50 mg/ml HRaman spectroscopy was conducted using a 532 nm laser (WITec Alpha 300R) on both as-grown and transferred graphene samples. Unless otherwise stated, the synthesized graphene was analyzed along the length (every 75 mm) and width  of the substrate using Raman spectroscopy directly on the Cu foil. Spectroscopy measurements were collected using a 1 sec integration time, and background values were subtracted from the resulting data using a polynomial fit function. A Lorentzian peak-fitting algorithm was used along with a low-pass filter to generate spectra for further analysis. Two-dimensional Raman scans were conducted using the WITec Alpha 300 R and a 35 μm × 35 μm area of interest, 45 × 45 pixels, and an integration time of 0.5 sec for each data point. Optical microscopy was also performed on the WITec Alpha 300R system. FE-SEM secondary electron images were acquired using a Zeiss Supra55VP FESEM operated at 2–5 kV.A.J.H. and E.S.P. conceptualized and designed the concentric tube CVD system, which was built by E.S.P. E.S.P. fabricated graphene films; E.S.P. and D.Q.M. performed optical microscopy, Raman spectroscopy and corresponding analysis; E.S.P., B.V. and S.W.P. performed scanning electron microscopy; E.S.P. and D.Q.M. performed graphene transfer; and A.J.H. supervised the research. E.S.P., D.Q.M. and A.J.H. wrote the manuscript. All authors discussed the results and reviewed and commented on the manuscript.How to cite this article: Polsen, E. S. et al. High-speed roll-to-roll manufacturing of graphene using a concentric tube CVD reactor. Sci. Rep.5, 10257; doi: 10.1038/srep10257 (2015).


The development of treatments for idiopathic pulmonary fibrosis (IPF) has been often disappointing. Building on authorized treatments that can benchmark the validity of treatment effect measures, the time has come to standardize endpoints and achieve consensus on their use for different clinical questions and specific IPF phenotypes. In order to facilitate the development of new medicines for IPF it is crucial that the knowledge of the disease and lessons learnt from past trials are taken forward to create international trial networks with involvement of patients, including biobanks and clinical data collection through a multinational registry. Interaction with regulators may be useful to align the initiatives of academia and pharmaceutical companies with the bodies ultimately responsible for licensing new products. Interaction can occur through the use of qualification programs for biomarkers and endpoints, and participation in innovative regulatory pathways and initiatives. Finally, the experience of IPF should be used to benefit even rarer interstitial lung diseases for which no treatment is available, including pediatric interstitial lung diseases. This commentary provides a perspective on the hurdles slowing the development and regulatory approval of medicines for IPF, and encourages close cooperation between investigators and drug regulators. The development of new medicines is characterized by very high attrition rates, with up to 10,000 compounds failing to show clinical efficacy per each new medicine reaching the market. Failure occurs mainly during translation from preclinical to clinical development and in clinical phase II, with efficacy rather than safety the most common cause of attrition . The resIn this landscape, until recently no pharmacological treatment was available for idiopathic pulmonary fibrosis (IPF), a rare disease of largely unknown cause with median survival estimated at about 3 years from diagnosis . After aWhile pirfenidone and nintedanib have proven to slow the decline of lung function in the clinical trials on which their approval was based , their eTo date, 12 medicinal products, most in preclinical phase of development, have obtained orphan designation from the European Medicines Agency (EMA)  for the Traditionally, pharmaceutical development starts with the selection of scientifically robust therapeutic targets and of the compounds with the highest activity on the selected target(s). While this may still be valid in diseases characterized by good correlation between genotype, molecular phenotype, and clinical phenotype, in complex trait diseases such as IPF, determined by multiple genes and variable influence by the environment, drug discovery tools commonly used to select and validate targets at preclinical level, such as high throughput compound profiling in cell-based assays , 14, mayAlternative approaches for identifying therapeutic targets in IPF should be encouraged, including those based on system biology and integrative omics. So far a handful of studies have investigated omics evidence in IPF, with hypothesis-generating results such as the discovery of genetic variants associated with alterations of lung host defense  (microbiWith translational failure of many IPF pharmaceutical pipelines, recurrent criticism arises toward the most widely used in vivo preclinical proof of concept, the bleomycin challenge rodent model. Indeed, none out of almost 300 compounds demonstrating efficacy in the bleomycin model was then efficacious in clinical trials . The modIn addition to the complexity induced by pathogenetic and clinical heterogeneity, the development of medicines for the treatment of IPF suffers from the hurdles characteristic of rare diseases, where small numbers of patients limit the feasibility of adequately powered trials, the validation of endpoints and biomarkers , and theThe recent consensus on imaging-based diagnosis  may faciA recent consensus group proposing provisional core sets of domains and instruments for clinical trials in connective tissue disease-related ILDs and IPF concluded that none of the proposed endpoints were ideal, or fully validated . Global Ideally, outcome measures would be chosen from among those that can be monitored in patients’ registries, to align measures of natural history of the disease with disease progression parameters measurable in clinical trials. Initiatives are ongoing at EMA to explore the use of registry data in the frame of regulatory procedures , in partAmong the initiatives facilitating the approval of new medicines, early access regulatory pathways, such as the adaptive pathway in pilot phase in Europe , aim to Global collaborative efforts are warranted to facilitate the development of new medicines for IPF, including data knowledge integration from genomics to clinical phenotypes. Lessons from past clinical trials should be used to create international trial networks with involvement of patients, including data collection through biobanks and a European registry, and for standardization of outcome measures. Interaction with the regulators for fostering the approval of new medicines can occur through qualification programs for biomarkers and endpoints, and participation in innovative regulatory pathways and initiatives. Finally, the experience of IPF should be applied to the development of medicines for ILDs for which no treatment is available, including pediatric ILDs.


The structural and electronic properties of twisted bilayer graphene (TBG) on SiC(000 In TBG, two layers are stacked with a variable twist angle between them. For large twist angles, the two graphene layers are electronically decoupled such that close to the Dirac point the electronic properties are identical to that of single layer graphene2345678910111213vf renormalization for small angles. Many studies181920vf renormalization. For instance, transferred graphene layers grown by chemical vapor deposition (CVD) with a 3.5° twist angle revealed a vf of 0.87 × 106 m/svf (0.82 × 106 m/s) for 3.1° twist angle involved few layer graphene on highly-oriented pyrolitic graphite (HOPG)vf compared to single-layer graphene. Another STM/STS studyvf for twist angles between 1° and 3°. ARPESμm lateral resolution ARPES study was recently reportedvf renormalization was observed at 2.7° twist angle. However, it is not clear if the signal shown in the μARPES images came from adjacent or stacked grains. The main drawback of these ARPES studies on multiple graphene grains is that the photoelectron intensity may originate from adjacent grains rather than from a single grain due to the large incident beam. So far, vf renormalization on twisted graphene remains an issue, which could be linked to the structure-dependent TBG electronic properties associated with the different elaboration techniques.On the experimental side, serious inconsistencies still remain on In this work, we address the electronic structure of single grains of TBG on SiC(000K point (at k|| = 1.703 Å−1) perpendicular to the Γ − K direction [see inset of −1π Dirac bands at the K point, along the corresponding Γ − K direction. Note, however, that imaging the same area for both azimuths is only possible if it is exactly at the center of rotation of the microscope. The N grains in Graphene single grains on SiC or with (II) moiré patterns as shown in As K − K′ direction, while only one side of each Dirac cone is observed when probing along the Γ − K direction, due to matrix element effectsK direction [see μm2 size). The electronic properties of TBG single grains were explored on a sample with a nominal thickness of 1.6 ML by nanoARPESK point of the graphene BZ for grains oriented along the W azimuth. These grains mainly contribute to the photoelectron intensity. However, because of the large angular distribution of the W orientation, graphene grains which are slightly misaligned with respect to the set azimuth also contribute to the signal. These experimental conditions also imply the observation of an apparent band gap when the measured grain and the set azimuth are not perfectly alignedμm2 which is much larger than the beam size (~120 nm). With the ANTARES nanoARPES set-up, individual TBG grains are probed, thus eliminating possible contributions from adjacent grains in the photoelectron intensity.When two graphene sheets are superposed with a relative twist, the corresponding BZs also rotate with respect to each other as illustrated in tion see  imply azK direction for grain 1. The corresponding measurement is shown in π bands are detected. The band A involves states up to the Fermi level EF, while the other one labelled B only appears for energies below ~ −0.65 eV. The occurrence of two bands was checked by performing a Lorentzian fitting analysis of the full width at half maximum (FWHM) of the experimental momentum distribution curves (MDC) [see −1 which is the typical value for a single π band−1)μm beam), where numerous grains contribute to the photoelectron intensity. This narrow FWHM validates the high spatial resolution capability of the k-microscope, such that single TBG grains could be probed. A larger width of 0.037 Å−1 is obtained at −1.4 eV, which is consistent with the occurrence of two bands appearing as one wider single band because their separation is lower than their FWHM. The fitted curve (light blue) for the MDC at −0.5 eV is superposed in EF and the band velocity deduced from the slope dE/dk close to the Dirac point is (1.1 ± 0.03) × 106 m/s, which is typical of monolayer graphene. For band B, yellow hollow circles deduced from the experimental maximum intensities of the MDCs are superposed as guides to the eye. These observations show that two bands are present in the E(k) dispersion in region 1. Band A is associated to the graphene layer oriented very close to the Γ − K direction of the set azimuth in the electron analyzer [analogous to the blue Dirac cone in K direction of the corresponding azimuth [analogous to the red Dirac cone in K direction (black dashed line). −1. The velocity is determined to be (1.06 ± 0.05) × 106 m/s for region 2.Using the microscope point mode, the nanoARPES E(k) dispersion was measured along the Γ − MDC) see . At −0.5θ in momentum space. They are centered at K and Kθ, as illustrated in The twist angle between the graphene layers can be quantified from the relative energetic positions of the two bands. In TBG, the Dirac cones are also rotated by the same angle KKΓ = 4π/3a. As shown in where E value extracted from the two Dirac cones is ~0.45 eV, which leads to a ΔKθ value of 0.062 Å−1 for the E vs. k plot in vf should be reduced to ~35% of the monolayer value 6 m/s) remains very similar to that of monolayer graphene. For the E(k) dispersion shown in K direction of the set azimuth. The energy maxima (relative to EF) for which the two bands are detected are respectively 0.58 and 0.32 eV. Using the same arguments and equations as above, the corresponding twist angles are 1.8° and 0.6° relative to a virtual graphene layer aligned along the set azimuth. Since the nanoARPES experiments do not give information on the relative angular position of the graphene layers, the corresponding twist angle is 1.8° ± 0.6°  appears larger than the one obtained by nanoARPES (~1–3°). Because of the energy range which was used, twist angles larger than ~4° could not be detected by nanoARPES  on multilayer samples. By measuring directly the band dispersion in single TBG grains, thanks to the high spatial resolution of the nanoARPES set-up, our results clearly evidence the absence of velocity renormalization for TBG on the C-face of SiC. Some previous works addressing this issue were performed using STS151617181920212223vf. Based on our results obtained for bilayer grains and on previous results for multilayers, one can conclude that no renormalization takes place in the twisted graphene on the SiC C-face, regardless of the graphene thickness. This imply that the graphene-graphene interaction in this system is almost negligible. On the other hand, the interaction of twisted graphene layers with metallic substrates191920vf as discussed below.The above findings clearly indicate that the predicted vf renormalization is based on the LLS studyf was 0.87 × 106 m/s for a twist angle of 3.5°. On the contrary, using similar LLS experiments on a different system, graphene on SiC C-facevf renormalization could be linked to the substrate material through its electronic structure, if the interaction between the substrate and the first layer could affect the interlayer coupling between twisted graphene layers. Indeed, following a LLS study on naturally decoupled TBG on HOPG, it was concluded that the interlayer coupling plays a significant role on vf renormalization14One experimental proof of n-type 4H:SiC dispersion at a fixed energy mode using an acceptance angle of 14° for a short integration time at each point in the scanned area, and then integrating the photoelectron intensity over E and k in the selected range.The STM studies were performed with a UHV Omicron NanoTechnology system. All images were recorded at room temperature in the constant-current mode using a W tip. The nanoARPES experiments were carried out at the ANTARES beamline at the SOLEIL synchrotron3334353637383940How to cite this article: Razado-Colambo, I. et al. NanoARPES of twisted bilayer graphene on SiC: absence of velocity renormalization for small angles. Sci. Rep.6, 27261; doi: 10.1038/srep27261 (2016).


This paper presents an comprehensive study of light trapping and absorption enhancement in graphene through metallic plasmonic structures and shows a strategy to realize both ultrabroadband and strong absorption enhancement. Three different plasmonic absorber designs are investigated by numerical simulations. The excitation of localized plasmons in the metallic structures significantly enhances the interactions between graphene and light at the resonances. By employing a splitted cross design for plasmonic resonant antennas and integrating two types of sub-antennas with different sizes, more than 30% of optical absorption in monolayer graphene is realized in a ultrabroad spectral range from 780 to 1760 nm. This enhancement functionality can be translated to any wavelength band from ultraviolet to terahertz ranges by modifying the geometric design of the plasmonic structure and can be applied for other two dimensional materials and their heterogeneous structures. It may significantly improve the efficiency of optical devices such as broadband photodetectors and solar cells based on graphene and other two-dimensional materials. In the past few years, graphene and other two-dimensional materials have emerged as promising materials for optics and optoelectronics1247910111416Many approaches have been proposed to enhance the absorption in graphene. One is placing it in an optical cavity, which enables light to pass through the graphene film multiple times. Different cavities have been employed including F-P microcavities182022232527283032343536In this paper, we investigate the light absorption of graphene integrated in plasmonic absorbers. Three different structures are studied and a strategy to realize ultrabroadband light trapping and absorption enhancement in graphene is proposed. It is shown that >30% light absorption by monolayer graphene can be realized in a spectral range from 780 to 1760 nm with the proposed design. The enhanced absorption is more than one order higher than that by a freestanding graphene film without enhancement.s = 80 nm and a metallic reflection mirror, respectively. The graphene film is in direct contact with the metallic crosses. The period is P = Px = Py = 550 nm. The insulator layer is assumed to be lossless with a refractive index of 1.5. The metallic crosses and mirror are made of gold. The thickness of the crosses are 30 nm. The incident light excites localized plasmons in the metallic structures, which trap light in the near-field and lead to strong absorption. As the graphene film is now integrated in the structures, a significant proportion of light will be absorbed by the graphene which will far exceed the absorption by a free standing graphene film.First, we consider the structure in 39Plasmonic resonators generally have an absorption cross-section bigger than its geometric size and multi-resonances can be realized by integrating two or more sub-resonators with different sizes in one unit cellIn the above structures, the graphene film is in direct contact with the metallic crosses. This is just the case for many demonstrated graphene photodetectors3435s = 2 nm, the resonant absorption in graphene decreases to 41.8%, 40.2%, 39.6%, 38.8%, respectively. They drop to 32.4%, 31.7%, 30.9%, 30.7% at the separation of s = 5 nm and 10.4%, 11.3%, 12.6%, 13.3% at the separation of s = 20 nm. However, the absorption in graphene can still exceed 13.8% in the spectral range from 780 to 1800 nm when the separation is s = 5 nm.Sometimes it may be necessary to have an insulator layer between the graphene film and the metallic plasmonic nanostructures . Besides monolayer graphene and other two-dimensional materials, heterostructures of two-dimensional materials with vertical stacks have attracted a great deal of attention for their potentials for optoelectronic applications. High-efficient and broadband photodetectors based on graphene double-layer heterostructures have been reported44In summary, we have numerically investigated three different plasmonic absorber designs for light trapping and absorption enhancement in graphene. The excitation of localized plasmons in the metallic structures can significantly enhance the interactions between graphene and light at the resonances. By employing a splitted cross design for plasmonic resonant antennas, dual resonances can be obtained in the studied spectral range. Furthermore, by integrating two types of sub-antennas with different sizes, the bandwidth for light trapping and absorption enhancement is effectively expanded due to multi-resonances. More than one order enhancement of optical absorption in a single layer graphene is realized in an unprecedented broad spectral range from 780 to 1760 nm. This enhancement functionality can be translated to any wavelength range from visible to terahertz by modifying the geometric design of the plasmonic structure and can be applied for other two dimensional materials and their heterogeneous structures. Besides, the proposed design is compact and suitable for integrated thin film devices which is an advantage over some other proposed methods for absorption enhancement in graphene4648G0 = e2/(4ħ) ≈ 6.08 × 10−5 Ω−1 which corresponds to the absorption of about 2.3% for a free standing film. The permittivity of gold was described by the Drude model with plasma frequency ωp = 1.37 × 1016 s−1 and the damping constant ωτ = 1.23 × 1014 s−1 which was three times larger than the bulk value considering the increased scattering by surface and grain boundary effects in the thin film.The numerical simulations are conducted using a fully three-dimensional finite element technique (in Comsol MultiPhysics). In the simulation, the graphene is modelled as a conductive surface with an optical conductance of How to cite this article: Xiong, F. et al. Ultrabroadband, More than One Order Absorption Enhancement in Graphene with Plasmonic Light Trapping. Sci. Rep.5, 16998; doi: 10.1038/srep16998 (2015).


LINE-1 (L1) retrotransposons are a source of endogenous reverse transcriptase (RT) activity, which is expressed as part of the L1-encoded ORF2 protein (L1-ORF2p). L1 elements are highly expressed in many cancer types, while being silenced in most differentiated somatic tissues. We previously found that RT inhibition reduces cell proliferation and promotes differentiation in neoplastic cells, indicating that high endogenous RT activity promotes cancer growth. Here we investigate the expression of L1-ORF2p in several human types of cancer.We have developed a highly specific monoclonal antibody (mAb chA1-L1) to study ORF2p expression and localization in human cancer cells and tissues.We uncover new evidence for high levels of L1-ORF2p in transformed cell lines and staged epithelial cancer tissues  while no or only basal ORF2p expression was detected in non-transformed cells. An in-depth analysis of colon and prostate tissues shows ORF2p expression in preneoplastic stages, namely transitional mucosa and prostate intraepithelial neoplasia (PIN), respectively.Our results show that L1-ORF2p is overexpressed in tumor and in preneoplastic colon and prostate tissues; this latter finding suggests that ORF2p could be considered as a potential early diagnostic biomarker. L1 retrotransposons comprise about 5 × 10e genome . Only 80e genome , wherease genome . Therefoe genome  and thate genome , 10; in e genome , with the genome , 13. In e genome , 15; in e genome , 16. Botin vivo in preclinical models. These findings were independently confirmed in several other laboratories after treating human cancer cell lines with both nucleoside [Furthermore, both RNAi-mediated downregulation of L1 expression  and the cleoside –19 and ncleoside –23 RT incleoside .We have recently proposed a model based on the central role of L1 RT in governing the balance between single- and double-stranded RNAs, through the formation of RNA:DNA hybrids. This mechanism hypothesizes that in cancer cells the generation of RNA:DNA hybrid molecules “subtracts” templates for double-stranded RNA formation and hence impairs the production of regulatory miRNAs, with a global alteration of gene expression , 25.Consistent with the idea that L1 RT is a key player in tumorigenesis, we recently found that ORF2p expression increases early at cancer onset in a transgenic murine model of breast cancer . This fiMost studies, aiming at the characterization of L1 proteins in human cancer tissues, have used antibodies directed against L1-ORF1p , 28, witRP-ORF2p [Aiming to analyze the expression of ORF2p in cancer, we produced a mouse monoclonal antibody against the human L1RP-ORF2p . BALB/c RP-ORF2p , using tRP-ORF2p . Third, RP-ORF2p   . To furtWe next evaluated the distribution of ORF2p in cancer cell lines of different origin. Protein extracts from several human cancer cell lines  were analyzed by immunoblotting using mAb chA1-L1 and compared to human non-immortalized normal WI-38 fibroblasts , ii) prostate (n = 54), iii) lung (n = 6), and iv) breast (n = 4) adenocarcinoma samples  and used the chA1-L1 antibody to compare L1-ORF2p expression levels with that of healthy, non-transformed counterparts. We found that 96% of all tumor samples are chA1-L1 immunoreactive, with signal intensities ranging from moderate (+) to very high (+++). In tumor biopsies that stained positive for ORF2p, 30–100% of all examined cells were reactive; no immunoreactivity was appreciated in any of the normal tissues analyzed  are shown in the scatter plot in Figure M) values ± SEM of signal scores assigned to the specimens . Data show a remarkably high mean value for signal scores (M = 41. 9) in transitional mucosa, increasing M values (from 27. 2 to 45. 8) in adenomas during progression from low to high grade, and high M value (M = 42. 5) in adenocarcinomas compared to normal tissues (M = 0). Thus, ORF2p expression does not only occur in advanced adenocarcinomas  in a scatter plot. Tissue samples were grouped according to histological features: Gleason grading of specimens (from 6 to 9) [M = 33,8), compared to Gleason 6, 7 and 8–9 adenocarcinomas  and to normal/hyperplasia tissues (M = 8. 3). Results are summarized in Table Figure  6 to 9)  derives de novo somatic insertions, which were found to be selectively present in tumor genomes [Growing data in the last few years confirm that cancer cells and tissues offer a highly permissive environment for the expression and mobilization of L1 retrotransposons. Numerous reports have consistently shown that the genomes of different cancer types harbor hundreds of  genomes , 44–48.  genomes . The fin genomes , 22, and genomes , supportIn that framework, it was mandatory to evaluate accurately the expression of L1-ORF2 RT in cancer tissues, since no systematic study had ever been carried out to this purpose. Here we have developed a highly specific monoclonal antibody, chA1-L1, raised against a peptide in the human ORF2p EN domain, the same domain that has been already targeted by others to generate both polyclonal and monoclonal anti-L1-ORF2p antibodies , 50. TheP < 0.001). Together, these data parallel other evidences demonstrating that genomic hypomethylation is an early event in colon tumorigenesis [Indeed, high ORF2p expression levels were observed at very early transformation stages in colon and prostate specimens, before the appearance of characteristic histological features of carcinoma Figures  and 6. Iigenesis  and thatigenesis . Moreoveigenesis , a findiigenesis  strengthigenesis , it is pIn staged samples from both cancer types analyzed in depth here, ORF2p appears to be stimulated in a bimodal pattern, with a sharp initial burst at a very early stage, followed by a second steady moderate wave throughout the latest stages. In our opinion, the present finding that L1-ORF2p expression precedes tumorigenesis further supports the view that high L1 activity could be a trigger of cell transformation rather than its consequence. In this context, early ORF2p expression could be regarded as a preneoplastic marker, at least in colon and prostate. Further work will establish whether ORF2p expression is a widespread early sign of transformation in diverse cancer types.In breast cancer studies, using murine models  and humaRP-ORF2p (accession number S65824) [spa-ORF2p sequence (accession number AAC53542.1) [® software (Life Technologies), in order to identify regions with the lowest homology (below 40%) between human and mouse L1 sequences. Six human peptides were selected:#39, aa 119–138:TGAPRFIKQVLSDLQRDLDS;#40, aa 231–248:SAIKLELRIKNLTQSRST;#41, aa 745–765:NNRQTESQIMGELPFVIASKR;#42, aa 945–962:RKLKLDPFLTPYTKINSR;#43, aa 980–1000:NLGITIQDIGVGKDFMSKTPK;#44, aa 1021–1044:TAKETTIRVNRQPTTWEKI FATYS.To raise mouse monoclonal antibodies against human L1-ORF2p, the amino acid sequence of L1 S65824)  was alig53542.1)  using VePeptides were synthesized, coupled to Keyhole Limpet Hemocyanin (KLH)  and used to immunize BALB/c mice . Mice were maintained at the Paul-Ehrlich-Institute, Langen, Germany, in accordance with the institutional directive on laboratory animal welfare. All animal experiments were approved (Permit F107/111) by the local authorities and performed according to ethical principles. Mice sera were tested for reactivity against all six immunogenic peptides by indirect ELISA assays and used in immunoblot analyses to test for the ability to detect proteins with a molecular weight (MW) of ∼150 kDa  in human 2102Ep embryonal carcinoma cell (ECACC: N2102Ep clone 2/A6) lysates. Mice with both high and specific humoral immune response were selected for splenectomy and the obtained B-lymphocytes were fused with X63Ag8.653 murine myeloma cells   were coated with 100 ng/well of each peptide; negative control wells were coated with BSA or a scrambled peptide; KLH was used as a positive control. Plates were blocked with 3% BSA / 10% fetal bovine serum in PBS, then incubated with mice sera diluted in blocking solution. To detect bound IgG antibodies, an HRP-conjugated goat anti-mouse IgG antibody  was added to each well. After addition of the substrate solution , the reaction product was quantified by light absorption (490 nm wavelength).Mycoplasma contamination using the Venor-GeM Mycoplasma kit (Sigma-Aldrich).A-375 melanoma cells ATCC CRL-1619), U-87 MG glioblastoma cells (ATCC HTB-14), A-375 melanoma cells stably interfered for L1 expression (pS-L1i) and their control cell line (stably transfected with non-interfering vector pS-neo) [described in 19, U-87 The pTT5-L1 plasmid, encoding codon-optimized L1-ORF2 which is expressed under the control of the CMV promoter and cloned between EcoRI and HindIII restriction sites , was gen6 cells were lysed in M-PER buffer (Thermo Scientific) supplemented with protease inhibitor cocktail (Roche). 50 μg of whole cell extract were used for immunoblotting as previously described [8 × 10escribed . mAb chAescribed  added to5 A-375 melanoma cells were grown on sterile coverslips in 6-well plates. Where indicated, cells were transfected as described above and fixed in cold methanol. Slides were blocked in 3% BSA, 0.05% Tween20 in PBS, 30 minutes at 37°C, then incubated with mAb chA1-L1 alone or in combination with a rabbit polyclonal anti-ORF1p antibody [5 × 10antibody  diluted Human bioptic tissue specimens were obtained from IRCCS San Raffaele Interinstitutional Multidisciplinary BioBank (BioBIM)  and Istituto Nazionale Tumori Regina Elena  or purchased as tissue microarrays . Informed consent was obtained from subjects enrolled in this study; all investigations were performed in accordance with ethical principles embodied in the Declaration of Helsinki.Formalin-fixed paraffin-embedded human tissue sections and microarrays were deparaffinized, rehydrated in descending graded ethanol solutions and treated with 0.6% hydrogen peroxide in methanol. Heat-induced antigen retrieval was achieved in Citrate buffer, pH 6.0 . Slides were pre-incubated with Protein Block reagent  for 1 hour at room temperature, and subsequently incubated overnight at 4°C with chA1-L1 mAb (8 μg/ml) in 1% BSA/PBS. Sections were stained using the Mouse Specific HRP/DAB (ABC) kit (Abcam), counterstained with Hematoxylin (Sigma-Aldrich), dehydrated in ethanol, mounted in Eukitt medium (Sigma-Aldrich) and visualized under a light microscope (Leica Microsystems) equipped with a cooled camera  and the IAS 2000 software for image capture.P < 0.05); statistical analyses were performed using the GraphPad Prism software.In an investigator-blind study, two researchers independently evaluated the stained human tissue sections. The percentage of ORF2p-positive cells  was calculated after scoring an average of five fields at 20x magnification; for overt carcinomas, histologically benign areas were excluded from the scoring. Signal intensities were classified as follows: –, same as background; ±, moderately higher than background; +, moderate; ++, high; +++, very high. Colon and prostate specimens were grouped according to histological features and signal intensities were scored (arbitrary units from 0 to 50) according to the following criteria: –, score 0; ±, score 10; +, score 25; ++, score 37,5; +++, score 50. Scatter plots show distributions and mean (M) values ± SEM of assigned signal scores; signal intensities corresponding to mean values are further indicated in Table


The dependence of the wettability of graphene on the nature of the underlying substrate remains only partially understood. Here, we systematically investigate the role of liquid-substrate interactions on the wettability of graphene by varying the area fraction of suspended graphene from 0 to 95% by means of nanotextured substrates. We find that completely suspended graphene exhibits the highest water contact angle (85° ± 5°) compared to partially suspended or supported graphene, regardless of the hydrophobicity (hydrophilicity) of the substrate. Further, 80% of the long-range water-substrate interactions are screened by the graphene monolayer, the wettability of which is primarily determined by short-range graphene-liquid interactions. By its well-defined chemical and geometrical properties, supported graphene therefore provides a model system to elucidate the relative contribution of short and long range interactions to the macroscopic contact angle. The surface fraction of suspended graphene is varied from 0% to approximately 95% by controlling the morphology of the textured substrate, which allows quantifying the effect of water-substrate interactions on the wettability of graphene. Further, we develop a novel procedure for transferring graphene to a solid support that obviates the irreversible contamination associated to polymer-assisted transfer. The water contact angle on both fully supported and partially suspended graphene depends marginally on the chemical nature of the substrate and the suspension fraction, albeit suspended monolayers are slightly more hydrophobic than supported ones. We show that the wettability of graphene is dictated primarily by water-graphene interactions and to a much lesser extent by water-substrate interactions. By its well-defined chemical and geometrical properties, supported graphene therefore provides a model system to elucidate the relative contribution of short and long range interactions to the macroscopic contact angle8Despite considerable progress, a comprehensive and consistent understanding of water-graphene interactions is still lacking. Bridging this gap requires the characterization of the intrinsic wetting properties of a suspended graphene sheet in the absence of any interactions with the supporting substrate. However, this is experimentally challenging since capillary forces exerted by macroscopic drops on the graphene membrane may either tear it or fold it. Here, we circumvent this limitation by preparing graphene monolayers partially supported on nanopatterned silicon substrates over macroscopically large (cm2), nanopatterned silicon surfaces with uniform feature size and spacing on a 10-nm length scale using block copolymer self-assembly and plasma etching (w ~ 5 nm) or flat (w ~ 15 nm to w ~ 30 nm) tips were obtained using a block-copolymer mask with cylindrical morphology and by varying the vertical and lateral etching rates (w~12 nm to w~20 nm at the top) were obtained using a block copolymer mask with lamellar morphology  graphene films without compromising its mechanical integrity2022Supported and partially suspended graphene monolayers were transferred from copper foils bearing graphene grown by chemical vapor deposition (CVD)18345The quality of the layers transferred onto flat and nanopatterned silicon substrates was assessed by optical microscopy, atomic force microscopy (AFM), Raman spectroscopy and scanning electron microscopy (SEM). The overall integrity of the graphene layer deposited on flat silicon is preserved during the transfer procedure leaving large areas available for contact angle measurements. However, contrary to polymer-assisted transfer methods, the graphene monolayer exhibits wrinkles most likely caused by surface tension forces acting on the floating layer after the copper foil is etched away . These wϕs < 15% 222325While our graphene monolayers are free of polymer contamination, adventitious carbon readily adsorbs on graphene exposed to ambient air and alters its intrinsic wettabilityThe protocol for reproducible contact angle measurement was optimized on graphene monolayers transferred onto flat silicon dioxide from three different commercial CVD-grown graphene sources see . Advanci102 annealing significantly modifies the wettability of flat SiO2 substrates. We have found that the flat silicon samples were completely wet by water after piranha cleaning (2 samples ϕs (red filled and red open circles respectively). These results show that the surface roughness enhances either the hydrophilic or the hydrophobic character of the substrates. For the sharper structures (ϕS < 10%), the contact angle was found to be a few degrees for hydrophilic substrates whereas it reached 165° for the hydrophobic ones, typical of super-hydrophilic and super-hydrophobic surfacesr is the roughness ratior = 5 − 10), and intrinsic hydrophilicity (2). Conversely, no such film was observed ahead of the droplet contact line on hydrophobic textures. In this case, wicking is suppressed by the surface hydrophobicity (2) and the droplet remains suspended on the texture.In order to investigate the influence of a graphene layer on the wetting properties of a substrate, we first characterized the wettability of the bare nanopatterned substrates. The measurements were performed on bare parts of the samples supporting graphene to ensure that both situations (with and without graphene monolayer) were subject to identical surface treatments and that wettability differences can therefore be attributed to the graphene influence. In particular, the Ar/HθS of the bare patterns, denoted as θS using the Cassie-Baxter (CB) equationBased on these observations, we have modeled the contact angle of wettability θT is the contact angle on the textured material, and θV the contact angle on the medium filling the texture voids, i.e. water (θV = 0°) or air (θV = 180°) for the hydrophilic and hydrophobic textures, respectively. The CB model is plotted against the data in θT = 55°, 105° for the hydrophilic (solid green line) and hydrophobic (green dashed line) pattern, respectively. The good agreement between theory and experiment suggests that the CB model describes adequately the wetting of the whole range of complex composite surfaces studied here.where θGS of water on the graphene layers transferred on the same nanostructures. On hydrophilic substrates, the optical observation of the droplets revealed features similar to the ones obtained on bare substrates resulting from the liquid impregnation of the textured surface beneath the graphene layer ahead of the contact line .Next, we measured the contact angle act line . EvaporaϕS < 25%, resulted in a smaller number of reliable measurements on hydrophobic samples than on hydrophilic ones. Optical imaging of water droplets deposited on graphene supported by hydrophobic textures showed that the liquid does not spread ahead of the contact line  in supported graphene sheets amounts to ~2% on flat supports and up to 8% on nanocone textures. These defects influence θGS depending on the wetting properties of the underlying substrate. On a superhydrophilic substrate, a hole in graphene locally creates a strong wetting defect, whereas on superhydrophobic substrates it gives rise to a strong non-wetting defect. These two types of defects are clearly visible in close-up viewgraphs of the contact line shown in ϕS thereby mimicking the experimental results. We have modelled this effect using the Cassie-Baxter equation , may account for up to 30% of the decrease of θGS measured on these substrates.We can rule out the possibility that the weak dependence of θGS on the composition of the supporting substrate therefore reflects changes in water-graphene-substrate interactions, rather than the spurious effect of graphene defects. An important finding of this work is that the wettability of graphene varies very little even when it is supported by materials with very different chemical composition such as air, water, silicon dioxide, and fluorinated silicon oxide. This implies that θGS is dictated, to a large extent, by water-graphene interactions and, to a lesser extent, by long range water-substrate interactions through the graphene layer.The dependence of Raj et al. who reported no influence of the underlying (hydrophilic) substrate and from a study by Shih et al.θS > 90°) but showed some degree of transparence for hydrophilic substrates (30° < θS < 90°). A combined influence of graphene and underlying substrate was also shown6These findings partially differ from the results of θGS, as a function of the cosine of the contact angle on the bare substrates, cos θS. Indeed, cos θGS is related to the water-graphene-solid effective interaction potential per unit area WWGS through the Young-Dupré equationIn order to relate quantitatively the observed wetting translucency of graphene to the underlying molecular interactions, we have plotted the cosine of the contact angle of supported graphene, cos γ is the surface tension of water. θS ≅ 1. The scattering of data in this region is likely due to the larger density of graphene defects on hydrophilic nanocone textures (ϕd ~ 8%).where θG = 85° ± 5° (for cos θs =−1), and graphene floating on water, θGW = 61° ± 5° (for cos θs = +1). Our results are well described by recent mean field calculations of water wetting a flat graphene sheet suspended on a rough substrate assuming dispersive interactionsθ = θGW − θG = −24° is in close quantitative agreement with et al.A linear fit to the data (solid black line) allows extrapolating the water contact angle on two ideal cases: totally suspended graphene θGS  =  θS. Hence, the contact angle of water on HOPG can be determined graphically as the intersection of the linear fit to the data with the cos θGS = cos θS line  = −WWS, water on graphene: γ(1 + cos θG) = −WWG, and water on supported graphene γ(1 + cos θGS) = −WWGS = −WWG − αWWS, where WWS and WWG are the water-substrate and water-graphene effective interaction potentials per unit area and we have also assumed that WWGS can be linearly decomposed as WWGS ≅ WWG + αWWS. α represents a phenomenological “screening parameter” that quantifies the degree of graphene transparency such that α = 0describes a perfectly opaque layer. Solving these equations for cos θGS yields:The linear relationship between cos α = 0, 21 ± 0, 03, or α = 0, 19 ± 0, 03 when a 2% defect density is taken into account  liquid-graphene interactions. Only ~20% of the long-range interactions between the liquid and the substrate are transmitted through graphene. Our findings shed new lights on the role of liquid-solid microscopic interaction on macroscopic quantities such as the contact angle. They are also relevant to many technological applications of graphene including advanced coatings3637The nanopatterned and flat substrates were degreased by sonication in successive baths of acetone, isopropyl alcohol and water. The samples were then immersed in a 40 mL mixture of hydrogen peroxide and sulfuric acid (1:3 v/v) for 15 minutes, thoroughly rinsed with deionized water and dried with nitrogen. This surface treatment results in highly hydrophilic substrates.In order to obtain the (super)hydrophobic substrates, the substrates were left overnight in a mixture of 10 mL hexadecane, 1 mL choloroform and 133 μL of 1H-1H-2H-2H-perfluorodecyltrichlorosilane  under Ar atmosphere. The substrates were then rinsed in chloroform and dried with nitrogen.2 as-synthesized piece of graphene-coated copper foil is floated at the surface of a dilute aqueous solution of copper etchant ((NH4)2S2O8) with graphene exposed to air (see −2 M) were used to promote a slow, steady etch rate (<500 nm/h) necessary to prevent the fragmentation of the copper foil into sub-millimeter grains, which may tear and sink the floating graphene layer. After complete dissolution of the copper foil (48–72 h), the graphene monolayer is left floating intact at the liquid-air interface. Although this process is performed in cleanroom environment, adventitious contamination on CVD-grown graphene typically provides enough reflective contrast to see the monolayer floating on the etching solution with the naked eye. The floating graphene is then carefully scooped out onto a rinsing bath of deionized water using a glass slide pre-cleaned in a mixture of hydrogen peroxide and sulfuric acid (1:3 by volume). After typically 15 minutes, the graphene layer is again scooped out of the rinsing bath using the final substrate. In the case of flat and patterned hydrophilic substrates, this step is greatly facilitated by the solution that wets the substrate completely. However, the deposition on hydrophobic substrates is more challenging because water spontaneously dewets these surfaces. We obviated this issue by adding a small amount of isopropanol (12% v/v) to the rinsing bath of distilled water thereby lowering the surface tension of the solution enough to induce complete wetting on the hydrophobic surfaces. After the transfer was completed, the samples were dried at room temperature.In our investigations we have used commercially-available graphene monolayers  grown on copper surfaces by chemical vapor deposition (CVD). A ~1 cm air see . A large2 atmosphere. The samples were heated up to 350 °C following a ramp of 5 °C/min, under a argon flux of 300 sccm, and kept at this temperature during 4 hours with an additional flux of hydrogen (75 sccm). The oven was naturally cooled down to ambient temperature under Ar flux.Prior to any contact angle measurements, the samples were cleaned by annealing under a Ar/HThe samples were first characterized using an optical microscope (Olympus BX60) and scanning electron microscope (FIB-SEM Zeiss 1540XB). Micro-Raman spectra were acquired on a Horiba Xplora-MV2000 spectrometer. AFM characterization were performed on a Multimode 8 AFM (Bruker) in Tapping mode using OTESPA cantilevers. The contact angle measurements were performed on a Kruss DSA100 goniometer following the procedure detailed in i.e. within 5 minutes after the last peeling. The obtained values were reproducible leading to θHOPG,adv = 62, 4° ± 0, 9° and θHOPG,rec = 60, 2° ± 1, 1°.The wettability of HOPG was characterized using a 10 × 10 × 1 mm HOPG (type ZYA) sample purchased from Scientec (France). The sample was exfoliated several times using a scotch tape until a flat surface was obtained. All measurements were performed on freshly exfoliated surfaces θHOPG,adv = 90° ± 1°, 6° and θHOPG,rec = 51, 2° ± 1, 5°. This evolution gives a large increase of hysteresis that can be associated to the adsorption of airborne contaminants, similar to the ones affecting measurements on graphene monolayers.When left overnight under ambient conditions, the contact angles drastically changed to reach How to cite this article: Ondarçuhu, T. et al. Wettability of partially suspended graphene. Sci. Rep.6, 24237; doi: 10.1038/srep24237 (2016).


We report the femtosecond laser propagation in a hybrid graphene/silicon ridge waveguide with demonstration of the ultra-large Kerr coefficient of graphene. We also fabricated a slot-like graphene/silicon ridge waveguide which can enhance its effective Kerr coefficient 1.5 times compared with the graphene/silicon ridge waveguide. Both transverse-electric-like (TE-like) mode and transverse-magnetic-like (TM-like) mode are experimentally measured and numerically analyzed. The results show nonlinearity dependence on mode polarization not in graphene/silicon ridge waveguide but in slot-like graphene/silicon ridge waveguide. Great spectral broadening was observed due to self-phase modulation (SPM) after propagation in the hybrid waveguide with length of 2 mm. Power dependence property of the slot-like hybrid waveguide is also measured and numerically analyzed. The results also confirm the effective Kerr coefficient estimation of the hybrid structures. Spectral blue shift of the output pulse was observed in the slot-like graphene/silicon ridge waveguide. One possible explanation is that the blue shift was caused by the ultra-fast free carrier effect with the optical absorption of the doped graphene. This interesting effect can be used for soliton compression in femtosecond region. We also discussed the broadband anomalous dispersion of the Kerr coefficient of graphene. The optical nonlinearity of most materials is generally weak. For example, silica in fiber has a Kerr coefficient n2 which is in the order of 10−13 m2/W at the wavelength 1.0 μm141516172 of graphene without employing slow light or resonant structures.Recently, graphene has attracted enormous attention for photonic and optoelectronic applications. Besides its many other novel optical properties, graphene has broadband nonlinear optical response1011Schematic of the femtosecond laser propagation in the hybrid waveguide is shown in C1 ≈ 5.4 μm−1 and Where A 1.5 μm thick SOI wafer is used to fabricate the ridge waveguides with width of 1.5 μm and thickness about 0.4 μm . Graphenike mode  and  forike mode . The prodB is the Bohr radius, dgr is thickness of graphene, α is the fine structure constant, and dB ~ 1 Å and dgr ~ 3.4 Å, We estimate that Z is the intrinsic impedance and Z = 377 Ω, n2(graphene) ~ 10−12 m2/W at 1.56 μm, that is 6 orders larger than that of siliconn2(silicon) ~ 4.0 × 10−18 m2/W. With a monolayer graphene cladding on the ridge waveguide  is 1558 nm, the pulse width is about 300 fs with operating current 560 mA and the repetition rate is 60 MHz. Laser was coupled to the sample by a single mode fiber with a tapered tip (Chuxing Ltd.) and the output power from the tapered tip is about 10 mW. Transmitted wave was coupled to a single mode fiber which is connected with an optical spectrum analyzer (Yokogawa AQ6370).2. We assume that the light intensity and effective Kerr coefficient distribute homogeneously at this area, and thus can simplify the simulation to one dimension.Short pulse propagation in the waveguide was simulated by a one-dimensional finite-difference time-domain method2 and 200 nm Si3N4 on top of the graphene to enhance the light density at the graphene layer.Silicon ridge waveguides were fabricated from a 1.5 μm thick SOI wafer. The width of the waveguides is about 1.5 μm and the etched thickness is 0.4 μm. Single layer highly N-doped graphene  was transferred on the surface of the waveguide. Slot waveguides were formed by depositing 40 nm thick SiOHow to cite this article: Liu, K. et al. Ultra-fast pulse propagation in nonlinear graphene/silicon ridge waveguide. Sci. Rep.5, 16734; doi: 10.1038/srep16734 (2015).


Silicon was modified with a thin layer of polyaniline, which assisted the dispersion of graphene sheets by introducing π-π interaction. Using scCO2, well-dispersed Si/graphene composite was successfully obtained in a short time under mild temperature. The composite showed high cycle performance  and rate capability . This study provides a new approach for cost-effective and scalable preparation of a Si/graphene composite using scCO2 for a highly stable lithium battery anode material.The silicon (Si)/graphene composite has been touted as one of the most promising anode materials for lithium ion batteries. However, the optimal fabrication method for this composite remains a challenge. Here, we developed a novel method using supercritical carbon dioxide (scCO Silicon (Si) is considered one of the most promising candidates for anode material for lithium ion batteries because of its high theoretical capacity 4,200 mAh/g); however, the material undergoes large volume changes >300%) upon charge-discharge cycling, resulting in structural collapse and poor electrical contacts within the anode structure, leading to drastic capacity fading100 mAh/g;00% upon 4568910111213et al. prepared Si/reduced graphene oxide composite using PDDA-modified Si and obtained a specific capacity of 1205 mAh/g after 150 cycleset al. used 3-aminopropyltriethoxysilane to modify the Si surface for further reaction with epoxy and carboxyl groups present in GO. The prepared Si/reduced graphene oxide composite showed a specific capacity of 1,600 mAh/g after 50 cyclesHowever, there are problems associated with graphene composite systems. Mechanical mixing is generally applied for composite preparation; however, it is difficult to ensure a uniform distribution of the Si-based particles over the surface of the graphene due to the insufficient interpenetration capability within the stacked graphene structure1516171519202) has attracted sustained interest in both the scientific and industrial fields because of its low critical temperature and pressure, as well as it being nonflammable, nontoxic, inexpensive, and environmentally benign2, because it can easily penetrate graphite, similar to gas, and stabilized the graphene by preventing aggregation. However, the graphene is easily aggregated through van der Waals interactions after depressurization, and agents such as polymers or surfactants should be used to prevent the formation of covalent bonds between the graphene2 fluid25et al. reported a graphite and PANi composite prepared using scCO2, in which PANi particles were homogenously deposited between graphite layers with aid of the π-π interactions between PANi chains and graphite layers2 fluid; however, to the best of our knowledge, few studies have tried to prepare Si/graphene composite, which might be due to highly reactive nature of Si precursors.Recently, supercritical fluid has been used in many studies to prepare graphene or graphene composite because of its gas-like diffusivity, liquid-like density, low viscosity, and zero surface tension2, we obtained a homogenous composite under a mild condition in a short time. We used graphene nanoplatelets instead of GO, which were prepared without an oxidation process, providing the advantages of lower cost and higher stability due to the absence of defects282 in order to deposit the nanoparticles on the graphene sheets through the π-π interaction between the graphene and PANi shell. The composite structure was fully characterized, and its electrochemical performance as a lithium battery anode material was carefully analyzed.Here, we demonstrate a strategy for fabricating Si/graphene composite using Si nanoparticles. With the aid of scCO2 with stirring and then dried to prepare the composite powder (SPG-sc). For comparison, the solution was mechanically mixed using an ultrasonication instrument (SPG-u) instead of scCO2. Graphene contents were varied for the initial optimization process; based on these results, graphene content was set at 30 wt% for further analyses. When a Si nanoparticle was covered by PANi, the color of the particle changed from light to dark brown , X-ray photoelectron spectra (XPS), Fourier-transform infrared spectroscopy (FT-IR), and thermo gravimetric analysis (TGA), as shown in 30 surface , a peak −1 ; these conditions are much milder than those for other solvents such as water (Tc = 347 °C and Pc = 221 bar) or ethanol (Tc = 243 °C and Pc = 61 bar). Finally, it is possible to fabricate the composite without chemical or physical variation of the components.To measure the mass variation of the composite during the modification process, TGA was conducted in air within the temperature range of 30–700 °C . The PANThe morphology of the prepared samples was investigated by scanning electron microscopy (SEM). Si nanoparticles had spherical shapes with an average particle size of approximately 100 nm . After cP/P0 range of 0.45–0.98, suggesting a porous structure of the composite. The BET specific surface area (SE) of the SPG composite was greater than 100 m2g−1, which might be due to the presence of graphene  method, showing that the pore volume of SPG-sc (0.635 cm3/g) was higher than that of SPG-u (0.278 cm3/g). Furthermore, plots of SPG composites showed wide distributions of pore size, from 2 nm to 30 nm , which causes Si nanoparticles to lose electrical contact from the electrode network422 showed a capacity of 1531 mAh/g after 50 cycles  and rate capability , which is attributed to the buffering of the elastic graphene framework and polyaniline shell. In addition, the porous structure provides additional space that is filled by expanded particles and efficient paths for the lithium ions, which are also critical factors for the improved cycle and rate performance.In summary, homogenous Si/graphene composite was synthesized with the assistance of a scCO2O) were obtained from Alfa Aesar. Aniline, ammonium persulfate  2S2O8), and hydric acid  were purchased from Aldrich. Graphene nanosheets (model: xGnP) of sub-micrometer to 100 lm in width and 1 nm to 15 nm in thickness were obtained from XG Sciences, Inc., Michigan, USA.Si nanoparticles (average particle size of ~100 nm) and poly(acrylic acid)  sonication instrument at 750 W for 1 h instead of using CO2. Also, SPG composite was also prepared by mechanical stirring, in which SP particles were not well dispersed  and transmission electron microscopy . The crystal structure and chemical composition were characterized using X-ray diffractometry  and X-ray photoelectron spectroscopy , respectively. Functional groups on the surface of the samples were characterized using a Fourier-transform infrared spectrometer , and the Brunauer−Emmett−Teller surface area was measured using a Belsorp-mini II apparatus .2) and weighed. The cell was fabricated in a glove box filled with high-purity argon gas using 1 M LiPF6 dissolved in ethylene carbonate/dimethyl carbonate/ethylmethyl carbonate as the electrolyte (volume ratio of EC/DMC/EMC = 1:1:1). The charge and discharge behaviors were monitored using a battery test system  with a voltage range of 0.005–3.0 V (vs. Li/Li+) at room temperature. Electrical impedance spectroscopy (EIS) measurements were conducted using a potentiostat , applying a 10 mV amplitude sine wave in the frequency range of 0.1 Hz to 100 kHz.Electrochemical properties of the prepared samples were measured using a 2032 coin-type cell. The active material (70 wt %), PAA as a binder (15 wt %), and carbon black as a conductor (15 wt %) were carefully mixed in a water/ethanol solvent. The slurry was then cast on Cu foil and dried at 80 °C under a vacuum for 12 h to remove the solvent. The electrode film was punched into 15-mm-diameter discs .


Biological markers, i.e., biomarkers, in lung tissue may make it possible to connect cell biological phenomena to the pathogenetic mechanisms in idiopathic pulmonary fibrosis (IPF). This review focuses on the lung tissue biomarkers, which have been compared with relevant clinical endpoints or with the most common differential diagnostic lung diseases. In addition, studies conducted on lung tissue samples and investigated by transcriptomic or proteomic methodologies have been included. Several studies have observed changes in alveolar epithelium and extracellular matrix supporting the current hypotheses of the pathogenesis of IPF. In many studies, however, alterations in inflammatory cells have been revealed, a phenomenon not currently incorporated into pathogenetic theories. Combining lung tissue material with other non-solid organs with clinically meaningful endpoints may prove to be the most beneficial approach in the search for non-invasive biomarkers. Biological markers, which are often referred to as biomarkers, are commonly defined as objectively measured and evaluated indicators of physiological or pathological processes or pharmacological responses to therapeutic intervention , althougIt has been estimated that about one third of IPF patients do require a surgical lung biopsy (SLB) in order to come to an ultimate diagnosis, and thus, it may be feasible to obtain lung tissue samples from a relatively high proportion of patients . One benThis review article aims to focus on biomarkers in IPF, i.e., idiopathic usual interstitial pneumonia (UIP), in lung tissue concentrating on studies with relevant clinical endpoints. Studies focusing on IPF and UIP were included due to the changes in the classification, which have taken place during the past decades, although all UIP cases do not necessarily represent IPF. Publications comparing IPF with major types of ILDs like nonspecific interstitial pneumonia (NSIP) and connective tissue disease-associated ILD (CTD-ILD), which are the most common differential diagnostic dilemmas, were included. In addition, studies conducted on lung tissue samples using modern large-scale transcriptomic and proteomic technologies were included, although all of those had not used clinical or radiological endpoints.The specific aggregates of fibroblasts, myofibroblasts, and extracellular matrix (ECM) proteins in fibrotic lung are called fibroblast foci (FF), and these structures are more common in IPF than in other types of lung fibroses. Several studies have demonstrated that a high amount of FF in lung tissue correlates with the shortened survival of IPF patients -12, as pThe majority, 75.8%, of patients with IPF were found to be positive for protease-activated receptor 2 (PAR-2) in the study of Park et al. Table . Blood nTodd et al. studied IPF cases using both SLB and subsequent lung transplantation samples from each patient, which made it possible to compare the histological features of the early and late phases of the disease. It was revealed that numbers of lymphocytes in lung tissue increased during progression since the amount of lymphocytes was higher in the lung explants than in the SLB samples .IPF cases were investigated for the expression levels of alpha smooth muscle actin (α-SMA), telomerase, interleukin 4 (IL-4), transforming growth factor-beta (TGF-β), and beta fibroblast growth factor (β-FGF). It was noted that the levels of expressions of myofibroblast α-SMA and IL-4 were negatively associated with patient survival . CalabreIt was noted that the number of mast cells were increased in IPF, and in addition, a high mast cell number also associated with a slower rate of decline in FVC in a study of Cha and co-authors . Nagata Myllärniemi et al. investigated UIP and NSIP cases for gremlin and bone morphogenetic protein 4 (BMP-4), revealing that the area of gremlin-positive staining correlated negatively with FVC. The levels of gremlin mRNA correlated negatively with the specific diffusion capacity corrected for alveolar volume (DLCO/VA), whereas BMP-4 mRNA correlated positively with FVC and DLCO . A negat2). Positive and statistically significant correlations were found between the numbers of CD8-positive TLs and alveolar-arterial gradient (P(A-a)O2) as well as the Medical Research Council (MRC) score. Furthermore, the CD8-positive TLs displayed significant negative correlations with the FVC% predicted and the FEV1% predicted [Parra et al. revealed that the total density of inflammatory cells was significantly increased in the patients with NSIP and diffuse alveolar damage (DAD) when compared to those with UIP. In UIP, forced expiratory volume in 1 s (FEV1) and survival correlated with the numbers of CD3-positive T lymphocytes (TL), the numbers of CD68-positive cells correlated with FEV1, and the amounts of neutrophil elastase-positive cells correlated with residual volume and residual volume/total lung capacity (TLC) and carbon monoxide transfer factor. The most important predictor of survival in UIP/IPF was CD3-positive TLs . In anotredicted .Tsukamoto et al. observed that epithelial cells were positively stained for Epstein-Barr virus-associated latent membrane protein 1 (LMP1) in 31% of the patients with IPF, whereas none of the patients with systemic sclerosis (SSc)-associated ILD or the controls showed this kind of positive staining. Death from respiratory failure was significantly more common in LMP1-positive patients than in LMP1-negative patients. The use of systemic steroids after lung biopsy was more frequent in the LMP-positive than in the LMP-negative patients .The amount of tenascin-C was analyzed in patients with UIP and also other types of ILDs . The meaCipriani et al. investigated CTD-UIP and IPF to evaluate the count and area of both FF and lymphocyte aggregates (LAs) Table . They foThe levels of epimorphin protein and mRNA expression in NSIP were significantly higher than those in the patients with UIP in the study of Terasaki and co-authors . NakashiZuo et al. conducted a microarray analysis of lung specimens from the patients with IPF and CTD-UIP Table . A markeYang et al. profiled lung tissue from the patients with sporadic pulmonary fibrosis and patients with familial pulmonary fibrosis. The genes involved in ECM turnover, ECM structural constituents, proteins involved in ECM degradation, and cell adhesion molecules were increased. Most of the genes that were differentially expressed in the familial IIP belonged to the same functional categories as those that distinguished IIP from control samples, but they were over- or under-expressed to a greater extent in familial IIP than in all cases of IIP .Konishi et al. evaluated lungs from the patients with stable IPF and patients with acute exacerbation of IPF (IPF-AEx) by microarrays. When compared with control samples, the global gene expression patterns of IPF-AEx were almost identical to those of stable IPF. In the direct comparison of IPF-AEx and stable IPF, the differentially expressed genes included those related to stress responses such as heat shock proteins and α-defensins as well as mitosis-related genes including histones and cyclin-A2 protein (CCNA2) . The stuYang et al. conducted a microarray analysis of 119 IPF cases and 50 controls. There was elevated expression of the cilium genes associated with microscopic honeycombing as well as higher expression of MUC5B and MMP-7. Two novel subtypes of IPF/UIP could be defined by the expression of cilium-associated genes . PatientA proteome analysis of explanted lungs from IPF patients identified that many proteins upregulated in the IPF fell into the related categories of unfolded protein response (UPR), endoplasmic reticulum (ER) stress, proteasome, degradation, and general cell stress response . SubsequPatel et al. studied IPF patients with pulmonary hypertension (PH-IPF) and IPF patients without PH (NPH-IPF). The comparison of PH-IPF arteriole with NPH-IPF arteriole results achieved no separation between the two groups. When gene expression of the combined IPF samples was compared to the controls, a total of 255 genes were differentially expressed in IPF arterioles . In a geThe current guidelines recommend that in the diagnostics of IPF, high resolution computed tomography (HRCT) has to be classified into three categories, i.e., 1) UIP, 2) probable UIP, or 3) not UIP . If otheThe recent workshop on IPF emphasized three research foci, i.e., 1) alveolar injury, 2) cellular origins of myofibroblasts, and 3) role of stem/progenitor cells . The preThe levels of SP-A in alveolar epithelium have been shown to be lower in UIP patients dying from progressive disease in comparison with the patients with a stable disease, a finding which may reflect dysfunction of AECII . The theTGF-β-induced enhancement of ECM plays a fundamental role in the pathogenetic theories of IPF. Gremlin, an antagonist of BMP, which is a member of the TGF-β superfamily, has been shown to associate with lung function parameters in IPF . High exMany immunohistochemical studies have detected changes in the numbers of inflammatory cells in lung tissue of IPF, a finding which is not markedly supported by the current hypotheses. A recent study revealed that the amount of inflammatory cells did not decrease during the progression of the IPF as previously assumed by many . MoreoveDuring the past decade, the research on IPF has focused on blood biomarkers, which is understandable since blood biomarkers can be easily obtained and analyzed, also repeatedly. At present, the most widely studied blood-derived biomarkers have been KL-6 and SP-A and -D . As outlStudying lung tissue in IPF is not an easy task when the missing key cell type or event in the pathogenesis of IPF causes discrepant analysis protocols in histological studies. Can we afford to ignore lung tissue samples when the pathogenesis of the disease and characterization of the phenotypes still leave so many unanswered questions? In addition to supplementing lung tissue material with other non-solid organs like blood, urine, and BAL, also the combination of multiple methods like omics, immunohistochemistry, protein assays, and mRNA quantification together with clinically meaningful endpoints may well prove to be the most beneficial approach with which to discover relevant non-invasive biomarkers. This kind of approach would hopefully make such progress so that within 10–15 years, rapid and reliable blood-based biomarkers will have become available not only for research purposes, but they will have become routine procedures also in clinical practice.