To study the impact of soluble IL2 receptor (sIL2R), chest x-ray (CxR), and angiotensin-converting enzyme (ACE) as markers for sarcoidosis in uveitis patients.Retrospective study.Serum concentrations of sIL2R and ACE were measured in patients with active uveitis. Those with elevated sIL2R and /or ACE values were examined for suspected systemic sarcoidosis.Our main outcome parameters were the specificity and sensitivity of sIL2R, CxR and ACE in screening for ocular sarcoidosis.We measured 261 patients with uveitis for sarcoidosis using sIL2R and ACE between January 2008 and November 2011; sarcoidosis was been diagnosed using other tests  in 41 of 53 patients with elevated sIL2R values (>639 U/ml) and in one patient with normal sIL2R (582 U/ml). Their mean sIL2R value was 1310 U/ml, extending from 582 to 8659 U/ml. Only 9 patients, however, presented elevated ACE (>82 U/l). Their mean ACE value was 116.4 U/l, ranging from 84.1 to 175.5 U/l. IL2R specificity was 94% with 98% sensitivity. In contrast, ACE had a specificity of 99.5%, but a sensitivity of only 22%; the chest x-ray had a specificity of 100% with 50% sensitivity in detecting sarcoidosis. We observed the entire spectrum of uveitis: sixteen patients suffered from anterior, 8 from intermediate, 16 from posterior, and 2 from panuveitis.An elevated level of soluble IL2R suggests sarcoidosis with uveitis more convincingly than ACE, making sIL2R a more effective marker parameter for sarcoidosis than ACE or chest x-ray in uveitis patients. Sarcoidosis or Morbus Boeck is a multisystem disorder of unknown cause,2,3. TheSarcoidosis is distributed worldwide and usually starts between the ages of 20 and 40 years. Its prevalence in the USA is three times higher in the Afro-American population than in the Caucasian population,14,15,16Untreated sarcoidosis may be fatal, and intraocular involvement can lead to blindness. The ophHowever, diagnosing it can be challenging. The golIn 2009, an international group of uveitis specialists therefore defined diagnostic criteria for ocular sarcoidosis, choosing criteria enabling the ophthalmologist to make the diagnosis of ocular sarcoidosis without the invasive diagnostic procedures needed for histological proof. These criteria included signs of intraocular inflammation and laboratory investigations.Not mentioned in these criteria is the soluble interleukin-2 receptor (sIL2R), a serum marker widely used for the diagnosis of and as an activity marker in pulmonary sarcoidosis,28,29,30Although its exact pathogenesis is unknown, sarcoidosis is characterized by T-cell activation,32,33. TThe aim of this study was to evaluate the potential clinical usefulness of sIL2R as a screening parameter for sarcoidosis with uveitis in comparison to established markers .Between January 2008 and November 2011, 600 patients were seen with uveitis for the first time in the uveitis section at the Eye Center, University of Freiburg. Out of these 261 were tested for sIL2R and ACE. In 53 of those we detected elevated sIL2R. All patients suspected of having intraocular sarcoidosis were referred to a respiratory specialist (pulmonologist).Medical data were reviewed retrospectively. We analyzed age, gender, comorbidity, current medications (including ACE inhibitors) and visual acuity.Anatomical location of the uveitis and its severity were classified according to the standardisation in uveitis nomenclature (SUN) criteria. In the We also collected chest radiographs, computer tomographies, bronchoalveolar lavage results, biopsies, and laboratory data. In accordance with the European Respiratory Society patients with alveolar lymphocytes ≥ 20% were considered to present a pathology. Due to Institutional Review Board (IRB)/Ethics Committee approval was obtained (Ethik-Kommission der Albert-Ludwigs-Universität Freiburg (No.69/14)). According to the IRB requirements patient records and information were anonymized and de-identified prior to analysis.ACE levels were determined by spectrophotometric assay using the synthetic tripeptide substrate N-[3-(2-furyl)acryloyl]-L-phenylalanylglycylglycine (FAPGG), which is catalyzed by ACE to FAP and glycylglycine (Roche). This hydrolysis results in a decrease in absorbance at 340 nm.Soluble IL2R was measured via a solid-phase two-site chemiluminescence immunometric assay . Soluble IL2R in the sample binds to the solid-phase antibody and reagent antibody , forming a sandwich complex. A chemiluminescent signal is generated in proportion to the bound enzyme. According to the manufacturer, the threshold value for ACE is 82 U/mL and 639 U/ml for sIL2R, respectively.Contingency table to achieve specificity, sensitivity, positive predictive value and negative predictive value of ACE, chest x-ray and sIL2R were calculated using Prism from the Graph Pad. The Youden Index, a marker of the performance of a diagnostic test, was also provided. FurtherThe patients with elevated sIL2R were classified in two categories: the first included all patients with ocular sarcoidosis, including 41 patients with elevated sIL2R and one patient with normal sIL2R value (582 U/ml) and in the second, those with elevated sIL2R and no evidence of sarcoidosis.The male/female ratio did not differ between these categories, and the median age was similar . Due to Mean ACE value was 59 U/ml in the sarcoidosis patients with uveitis (n = 41) while that of the uveitis patients without sarcoidosis (n = 220) was just 35 U/ml  (p<0.001The patients with elevated sIL2R/no sarcoidosis suffered from idiopathic non-granulomatous uveitis (6), from systemic autoimmune disease (3) (undifferentiated systemic autoimmune disease (2), lupus erythematosus (1)), mycoplasma infection (1), HLA B27 associated uveitis (1) or TINU syndrome  (1).Based on results from the chest x-rays, CT scans, tissue biopsies and IWOS criteria, we detected 42 sarcoidosis patients with uveitis. A diagnosis of definite ocular sarcoidosis was made in 10 patients, presumed ocular sarcoidosis in 12 patients, and probable ocular sarcoidosis in 19 patients. One patient was diagnosed with possible ocular sarcoidosis .We classified these patients according to the SUN criteria. Sixteen suffered from anterior uveitis, 8 from intermediate uveitis, 16 from posterior uveitis and two from panuveitis .Specificity was high for the chest x-ray, sIL2R and ACE. It was lowest for sIL2R at 94%. In contrast, the sIL2R sensitivity was 98%, chest x-ray 50%, and ACE only 22%. Thus positive and negative predictive values were favorable for all factors, but Youden Index was only favorable for sIL2R  .The eye is a potential primary and/or presenting site for the manifestation of sarcoidosis. Ophthalmologists play a critical role in establishing its diagnosis,46. In 2Serum angiotensin converting enzyme (ACE) is probably the most common laboratory test for sarcoidosis, revealing an approximate sensitivity of 57–73% and a specificity of 90% in the literature, but only 22% sensitivity and 90% specificity in our patients,49. EvenACE is secreted by epithelioid cells and macrophages and is thus a marker for the general burden of granulomas. ACE is An ideal marker would be one that is easy to obtain at any time and safe for the patient. The serum sIL2R value fulfills these criteria and is already frequently used in the clinical routine for diagnosing pulmonary and systemic sarcoidosis,29,30. IIn the present retrospective study, we assessed serum sIL2R in a group of patients with ocular sarcoidosis. On the basis of our data, we can claim that soluble IL-2R is a useful screening marker for sarcoidosis with uveitis. All kinds of intraocular uveitis  were detected as being associated with subclinical pulmonary sarcoidosis. Furthermore, we measured a sensitivity of 22% and a specifity of 90% for ACE. In direct comparison, IL2R seems to be the more appropriate screening tool for the diagnosis (sensitivity 98% // specificity 94%// Youden Index 92%). Soluble IL2R is a parameter that indicates the extent of T-cell activation and has been known since the early eighties,36. ElevAn increased IL2R level has been reported to be associated with uveitis. Few studies have demonstrated a relationship between sIL2R levels in peripheral blood and in aqueous humor with uveitis,59,60,61There are some limitations in our study; it is only a retrospective, single-center study. As mentioned above, there is no real gold standard available, thus we applied the IWOS criteria. Taking this into account, you will never even in a prospective study detect all true positives and false positives. Therefore, there will be always some degree of uncertainity.In addition, the performance of a test depends tremendously on the population in which it is assessed. The specificity would be less in a population with lower incidence of sarcoidosis.Nevertheless, our results clearly indicate that sIL2R levels are superior to ACE levels and CxR for identifying patients with sarcoidosis even if the study has the aforementioned limitations.In summary: based on our data; we recommend adding the measurement of sIL2R in the routine diagnostic work-up of patients with uveitis as an additional screening parameter for intraocular sarcoidosis. Moreover, already established biomarkers such as ACE and lysozyme may be replaced by sIL2R.S1 Dataset(XLSX)Click here for additional data file.S1 Table* p<0.0001; soluble Interleukin 2 Receptor (sIL2R); Angiotensin converting enzyme (ACE).(DOC)Click here for additional data file.


Moreover, while the in-plane stiffness only increases moderately when the devices are cooled down to 10 K, it approaches 300 N m−1 when the aspect ratio of graphene membranes is increased. These results indicate that softening of graphene at temperatures <400 K is caused by static wrinkling, with only a small contribution due to flexural phonons. Together, these results explain the large variation in reported mechanical constants of graphene devices and pave the way towards controlling their mechanical properties.Free-standing graphene is inherently crumpled in the out-of-plane direction due to dynamic flexural phonons and static wrinkling. We explore the consequences of this crumpling on the effective mechanical constants of graphene. We develop a sensitive experimental approach to probe stretching of graphene membranes under low applied stress at cryogenic to room temperatures. We find that the in-plane stiffness of graphene is 20–100 N m Free-standing graphene is inherently crumpled in the out-of-plane direction due to dynamic flexural phonons and static wrinkling. Here, the authors use optical interferometry as a delicate probe to investigate the consequences of this crumpling on the effective mechanical constants of graphene. E2D=340 N m−1 and vanishing bending rigidity. This record stiffness caused by strong carbon–carbon bonds13E3D∼1 TPa∼E2D/t, where t∼0.335 nm is graphite interlayer spacing461012What is the mechanical stiffness of free-standing monolayer graphene? The answer to this question may appear trivial: graphene is universally modelled as a flat sheet with in-plane stiffness (the ratio of in-plane stress and strain) et al.At the same time, the interplay between crumpling and mechanical properties of graphene remains virtually unstudied experimentally, despite its obvious significance for fundamental understanding of mechanics of two-dimensional (2D) materials as well as applications in graphene-based Nanoelectromechanical (NEMS) devices. We believe that the likely culprit is the technique used in the majority of the experiments probing graphene mechanics—atomic force microscopy (AFM) nanoindentation3714E2D to values of as low as ∼20 N m−1. Furthermore, by performing temperature-dependent measurements and studying devices of various geometries, we separately probe the contributions of flexural phonons and static wrinkles. Static wrinkling is found to be the dominant mechanism determining the effective mechanical constants in our devices. Finally, we discover an approach to suppress static wrinkling by in situ changing the membrane's geometry.Here we quantitatively investigate the effects of crumpling on the effective mechanical stiffness of graphene. To accomplish this, we develop a non-contact approach based on interferometric profilometry. This allows us to study the mechanics of graphene at cryogenic to room temperatures in a controlled geometry with uniform loading. We confirm that out-of-plane crumpling softens 3N4) with diameter ranging between 7.5 and 30 μm form the ‘sample chip'. Pristine residue-free graphene is seen in the high-resolution scanning electron microscopy (SEM) imaging of the sample chip . The applicability of parallel-plate capacitor approximation is justified since d∼10–20 μm is much larger compared with the maximum deflection of graphene (∼600 nm). The maximum Vg that can be applied without dielectric breakdown is ∼2,000 V, which allowed us to reach maximum pressures around 30 kPa; the uncertainty in P is below 5% for all voltages.Graphene was electrostatically pressured by applying a voltage h is determined with sub-nanometre precision in the out-of-plane direction and sub-micron resolution in the in-plane direction by detecting the phase shift of light reflected from the sample surface. Large graphene–gate separation d helps to maximize the interferometric signal from nearly transparent graphene. When d is large, only the signal reflected from graphene is detected since the gating chip is out of focus. A separate measurement is performed to find d by deliberately sweeping the focus from the sample to gating chip.The deflection of the graphene membranes under applied pressure was determined via interferometric profilometery. In this technique, a profile of the surface h, and verify that the membrane is deflecting symmetrically. Third, the pressure is applied uniformly, allowing us to use simple and reliable models to extract mechanical constants. Fourth, the optical nature of the technique allows simple characterization of devices inside an optical cryostat at low temperatures. At the same time, we note that our method is not a replacement for AFM nanoindentation. Our approach operates in the regime of low applied pressure and cannot be used to determine breaking strength of 2D materials.Our method of probing the mechanical properties of graphene has several critical advantages over AFM-based nanoindentation and other techniques. First, graphene deflection is measured via a non-contact approach. This means that the membrane morphology is not disturbed with a sharp tip that applies non-uniform stress. Second, the height data from the entire membrane is recorded at the same time. This means we can find the true maximum centre-point deflection, h versus known applied pressure P σr/ɛr, where ν∼0.165 is the Poisson ratio for grapheneE2D does not deviate more than 10% from the simple analytical estimate above  data to the bulge-test equation E2D=35±29 N m−1, consistent with previous workσr(ɛr), with E2D=(1–ν)dσr/dɛr increasing from less than 10 N m−1 at low stress to 50 N m−1 at higher stress  data between loading and unloading cycles (E2D for CVD graphene (E2D∼50–80 N m−1 in two devices). This confirms that E2D in our experiments is not affected by the grain boundaries in graphene, which is consistent with conclusions from previous experimentsE2D consistent with optical profilometry measurements. It is important to note that AFM nanoindentation pushes graphene towards the substrate, while electrostatic loading pulls graphene away from it. Similarity in E2D values obtained for opposite loading directions confirms that interaction of graphene with the sidewalls does not affect the measured E2D. Finally, simple estimates show that the organic residues that may remain on graphene after the fabrication process are unlikely to affect E2D. A uniform residue layer with Young's modulus of ∼2 GPa , we would expect strong stiffening of graphene at low temperature if this were the dominant effect. We measured two different devices in the range of temperatures between 400 and 10 K . This confirms that the changes in stiffness observed in Normally, the presence of defects lowers the mechanical stiffness of any material, including grapheneE2D measured in the experiment can be loosely approximated asIt is instructive to estimate relative contributions for flexural phonons and static wrinkling to the in-plane stiffness of our devices. The in-plane stiffness of graphene Elatt∼340 N m−1, Eflex and Ewrin are contributions to stiffness from three different mechanisms—stretching of carbon–carbon bonds, flexural phonons and static wrinkles. The data in E2D from 36 to 300 N m−1. Provided that the width of graphene ribbon is much larger compared with the typical wavelength of a flexural phonons, ∼10–1,000 nm, we expect that the process of cutting does not affect the contribution due to flexural phonons. We can then use Ewrin<40 N m−1 and Eflex>2,500 N m−1 from this data. In agreement with our earlier conclusion, we see that the contribution due to wrinkles dominates E2D. A simple estimate can clarify why the contribution due to static wrinkling is larger than that of flexural phonons. The degree of crumpling of a membrane can be quantified as ΔA/A=(A′–A)/A, where A is membrane's area, and A′ is the area of membrane's projection onto a plane parallel to it flex∼0.5%. This estimate agrees with ΔA/A extracted from molecular dynamics wrin∼π2δ2/λ2>0.1–1.6%. The lower bound here is likely a very conservative estimate as it neglects wrinkles with longer wavelengths. The corresponding ɛt from this estimate is larger than the average built-in strain observed in experiment, and we, therefore, do expect softening of graphene due to static wrinkling.The degree of crumpling of graphene due to flexural phonons can be estimated using a model based on the application of the equipartition theorem to the membrane-bending modesdynamics  and moreδ=1–2 nm  we estimσ0=0.02 N m−1 fits our data well  with uniform loading and at cryogenic to room temperatures. We have confirmed that graphene is significantly softened by out-of-plane crumpling. Moreover, we developed an approach to test relative contributions of flexural phonons and static wrinkles to the in-plane stiffness of graphene, and found that the latter dominates. Our observations reinforce the idea that great care is needed when applying classical elasticity theories to atomically thick materials372 environment at 350 °C. The fabrication yield for intact suspended graphene membranes varies from 55% for our smallest (7.5 μm diameter) devices to <8% for the biggest (30 μm diameter) devices. The graphene membranes remained clamped to the sample chip via van der Waals interactions forming suspended circular graphene membranes.Silicon nitride membranes (thickness 1 μm) were fabricated by depositing low-stress silicon-rich silicon nitride on both sides of a silicon chip. An array of holes ranging between 7.5 and 30 μm were then patterned in the nitride using standard fabrication procedures. A metallic contact  was deposited onto the top surface of the nitride membrane. Monolayer graphene was then transferred onto holes in the nitride membranes. Different transfer procedures were used for CVD and exfoliated graphene. For CVD graphene, we use a high-quality atmospheric growth and wet transfer3941A Wyko 9800 interferometric profilometer equipped with a 20 × ‘through transmissive media' objective (NA=0.28) was used to perform optical measurements. In measurements of graphene deflection, phase shift interferometry mode was used with HB-LED at ∼530 nm wavelength as illumination source. To measure graphene-gate separation, vertical scanning interferometry mode was used with white light illumination source.+ ion beam .The FIB lithography was carried out using a Novalab 600 Dual-Beam (electron/ion) FEI. The system is aligned to the graphene with the electron beam  while cuts are made with GaHow to cite this article: Nicholl, R. J. T. et al. The effect of intrinsic crumpling on the mechanics of free-standing graphene. Nat. Commun. 6:8789 doi: 10.1038/ncomms9789 (2015).Supplementary Figures 1-7 and Supplementary References


Exportin-1 (XPO1) is a nuclear export protein with >220 cargo proteins, including tumor suppressors and cell cycle modulators. Selinexor is a SINE (Selective Inhibitor of Nuclear Export) compound that has been administered to >900 cancer patients in Phase I and II trials to date, with evidence of efficacy and tolerability. Selinexor blocks nuclear export of NFAT1c, STAT1 and STAT3, which are implicated in regulating the inhibitory T cell receptor PD-1 and its ligand, PD-L1. We hypothesized that selinexor would upregulate T cell checkpoint molecule expression, and that combination treatment with anti-PD-1 or anti-PD-L1 would thereby enhance the ability of selinexor to elicit antitumor activity.in vivo study.Selinexor increased PD-1 gene expression by ~2-fold in normal lymphocytes and induced PD-L1 gene expression in tumor cell lines. Mice bearing syngeneic colon tumors (colon26) treated with selinexor and anti-PD-1 for 2 weeks demonstrated a significant reduction in tumor growth rate (P < 0.05), while monotherapy with either agent had no significant effect on tumor growth. Similar results were obtained in mice bearing syngeneic B16F10 melanoma tumors, whereby combined treatment with selinexor + anti-PD-1 was superior to either single agent alone (p < 0.034). Combined therapy of mice bearing B16F10 tumors with selinexor and anti-PD-L1 was similarly effective, with significantly smaller tumors at the study endpoint (p < 0.001). No weight loss or signs of toxicity were evident in any Immunophenotypic analysis by flow cytometry revealed that selinexor alone or in combination with anti-PD-1/anti-PD-L1 significantly increased the percentage of splenic NK cells (p≤0.050), while selinexor ± anti-PD-L1 significantly increased the percentage of splenic Th1 T cells (p≤0.011), all compared to vehicle treated mice. Interestingly, combining selinexor with anti-PD-L1 significantly decreased the percentage of splenocytes that expressed PD-L1 (p < 0.001). These data indicate that the efficacy of selinexor may be enhanced by disrupting the pre-existing PD-1/PD-L1 signaling in effector cells (T and NK cells).Altogether, these data suggest that the efficacy of selinexor in combination with anti-PD-1 or anti PD L1 in mouse syngeneic tumor models may be due to both disrupting immunosuppressive PD-1/PD-L1 signaling and increasing the frequency of potentially tumor reactive NK cells and Th1 T cells. This provides a rational basis for this treatment combination as a novel therapeutic approach for advanced cancer.


This paper presents a low-cost low-power CMOS humidity sensor for passive RFID sensing applications. The humidity sensing element is implemented in standard CMOS technology without any further post-processing, which results in low fabrication costs. The interface of this humidity sensor employs a PLL-based architecture transferring sensor signal processing from the voltage domain to the frequency domain. Therefore this architecture allows the use of a fully digital circuit, which can operate on ultra-low supply voltage and thus achieves low-power consumption. The proposed humidity sensor has been fabricated in the TSMC 0.18 μm CMOS process. The measurements show this humidity sensor exhibits excellent linearity and stability within the relative humidity range. The sensor interface circuit consumes only 1.05 μW at 0.5 V supply voltage and reduces it at least by an order of magnitude compared to previous designs. Passiveetc. . The pasetc. –6. Theseetc. [Humidity measurements are essential for a wide range of applications, including environment monitoring systems, process control systems, pharmaceutical and biomedical applications, food preservation, etc. . Humiditetc.  and resietc.  are the Various materials, such as porous ceramics and hygroscopic polymers, are used as humidity-sensitive materials . Becauseetc. However, analog IC is less scalable and suffers more when going to nanometer CMOS technology. Apart from the issues of matching and noise, the threshold voltage is reduced less remarkably compared to the power supply, resulting in a reduced voltage headroom for traditional analog amplitude-based sensor interfaces [CMOS technology has been mainly developed for digital IC. Benefitting from technology scaling, digital IC achieves great improvements on speed, power dissipation, chip area, terfaces . To copeterfaces ,22. ThisThe paper aims to present a low-cost low-power humidity sensor for RFID sensing applications. The rest of the paper is organized as follows: Section 2 presents a low-cost humidity sensor which is fabricated in standard CMOS technology without any further post-processing. Section 3 introduces the Phased-Locked Loop (PLL)-based sensor interface theory first and then illustrates the implementation of the fully-digital sensor interface in detail. The measurement results are presented and compared with previous designs in Section 4. Finally, some conclusions are drawn in Section 5.2.2 layer on the Si wafer. A thick aluminum layer is then deposited and patterned with standard optical lithography and wet etching over the SiO2 in order to form the interdigitated structure. The sensing film is polyimide that is coated on the interdigitated electrodes. In order for moist air to access the sensing film, there must be a large area of the polyimide exposed to the air. As is seen from L is the length of aluminum electrodes, S is the width of each electrode, and W is the distance between adjacent electrodes. The thickness of the polyimide layer is H, which is generally larger than the metal thickness h.For a CMOS process, interdigitated top metal fingers, with polyimide filled into the finger gaps, can be utilized for capacitive humidity sensing. The line-to-line coupling capacitance of the top metal is sensitive to the dielectric constant of the filling material. Furthermore, due to the high precision of photolithography, such kinds of sensing structures are highly reproducible with less inter-die variations . Figure wetε represents the dielectric constant of the polyimide film with absorbed water, γ is the fractional volume of water absorbed in polyimide, dryε is the dry polyimide film dielectric constant, and waterε is the water dielectric constant. The relationship between γ and relative humidity can be modeled by Daubinin equation [mγ is maximum factional volume at T0=298K, ф(T) is the temperature dependence on the adsorption coefficient and β(T) is the temperature dependence of the relative dielectric constant of water and the catalytic effect. The dielectric constant of the polyimide film wetε (and in turn the capacitance of the sensor) depends on the relative humidity, which increases or decreases when moisture penetrates or leaves the film. The mechanism for moisture absorption (or desorption) depends on the film properties (not sensor geometries) and determines the sensitivity of the sensor [The dielectric constant of the sensing film can be expressed by the Looyenga empirical equation  as folloequation  as folloe sensor .N finger array sensor, the total sensor capacitance can be expressed as [For a essed as :(3)CsenH has a great influence on the sensitivity and response time of the sensor. Generally, a humidity sensor with a thicker polyimide layer has better sensitivity and longer response time. Trading off the various factors, including sensitivity, response time, hysteresis performance and chip area, this work chooses N = 40, L = 200 μm, W = 2.5 μm, S = 2.5 μm, h = 1 μm and H ≈ 2 μm. The sensor capacitance can be evaluated in accordance with wetε is given.The selection of the thickness of polyimide layer 3.3.1.sensf. The frequency-demodulating block is a digital first-order Bang-Bang-Phased-Locked-Loop (BBPLL), consisting of a single-bit phase detector and a Digitally-Controlled Oscillator (DCO). This BBPLL measures whether sensf leads or lags digf (the frequency of the DCO) and hence the DCO is only steered by a single-bit signal outb. When the entire feedback loop is locked, sensf shifts between a maximum and minimum value which corresponds to the maximal and minimal value of the sensor. The average digital frequency digf will correspond to the sensor frequency sensf. Therefore, the over-sampled output outb represents the digital value of the sensor value.The architecture of PLL-based sensor interface, developed from Danneels , is showThis architecture employs the BBPLL block, which has advantages ranging from low voltage capabilities, low power consumption, small chip area, and scalability to smaller technologies and robustness to process variation ,29. Anot3.2.sensorC acts as the variable load on a single stage of the SCO, thereby generating a sensor-controlled frequency sensf. The variable capacitive load on a single stage of the DCO consists of two capacitors, oC and mC. The capacitor oC, designed equal to the quiescent value of sensorC, is always connected to the DCO. But the capacitor mC, designed slightly larger than the maximum variation of sensorC, is swapped in or out of the DCO depending on the feedback from the single-bit phase-detector. Considering the issues of system linearity and process variation, mC is normally designed as a programmable capacitor. The dummy load capacitor dC at each stage should be carefully designed to be small enough for high resolution performance.The implementation of the proposed fully-digital capacitive sensor interface is shown in sensf and digf are equal, thus the two frequency controls of the SCO and DCO are correlated. Since both oscillators are implemented identically, the control of the SCO, the sensor value, is correlated to the control of the DCO, the single-bit output of the phase detector. Hence the value of the sensor is digitized in this single-bit DCO control signal (outb). In order to increase resolution, outb is over-sampled by taking its average duty cycle overtime [As shown in overtime .oC and mC are selected as 5 pF and 2 pF, respectively. The dummy load capacitors (oC) at each stage are chosen to be 1 pF. Due to the fully digital architecture, the power supply of the interface is selected as 0.5 V, which is close to the process threshold voltage.For this work, the humidity sensor's capacitance varies from 5–6.5 pF within the relative humidity range. Hence the capacitors 4.2 and 0.008 mm2, respectively. Two test humidity sensors, with 1 μm-thick and 2 μm-thick polyimide layers respectively, were measured in a Votsch VCL4003  temperature and climate test chamber.The proposed humidity sensor, fabricated in the Taiwan Semiconductor Manufacturing Company (TSMC) 0.18 μm 1P6M mixed-signal CMOS process, is shown in sensorC) of the humidity sensor with 2 μm-thick polyimide layer at 25 °C. The measured outputs (dotted line) and the digitized over-sampled outputs (solid line) are shown together. It is obvious that the average duty cycle of the output increases in proportion to the value of ΔsensorC.The measured sensitivity of the humidity sensor is shown in versus relative humidity on the 1st, 8th, 15th day so as to study the repeatability of the humidity sensor with time. It is obviously that the humidity sensor exhibits excellent repeatability.The stability measurement of the humidity sensor is given in 5.The paper presents a integrated capacitive humidity sensor for RFID sensing applications. The humidity sensor is implemented in a standard CMOS process without any further post-processing, which results in low fabrication costs. The sensor interface, based on PLL architecture, transfers sensor signal processing from the traditional voltage domain to the frequency domain. It employs a fully-digital architecture and therefore can operate on an ultra-low supply voltage, which results in low power dissipation. The measurement results prove its excellent performance in the areas of linearity, stability, chip area and power dissipation. In particular the proposed sensor interface can work with 0.5 V supply voltage and consumes only 1.05 μW. Therefore this humidity sensor is particularly suitable for the mass-production of RFID sensing tags.


Flavonoids are also known to exert an inhibitory effect on the vascular endothelial growth factor receptor (VEGFR) family of tyrosine kinase receptors. VEGFR2 is one of the important receptors involved in the regulation of vasculogenesis and angiogenesis and has also been implicated to exhibit various neuroprotective roles. Its upregulation and uncontrolled activity is associated with a range of pathological conditions such as age-related macular degeneration and various proliferative disorders. In this study, we investigated molecular interactions of 7,8-DHF and its derivatives with both the TrkB receptor as well as VEGFR2. Using a combination of molecular docking and computational mapping tools involving molecular dynamics approaches we have elucidated additional residues and binding energies involved in 7,8-DHF interactions with the TrkB Ig2 domain and VEGFR2. Our investigations have revealed for the first time that 7,8-DHF has dual biochemical action and its treatment may have divergent effects on the TrkB via its extracellular Ig2 domain and on the VEGFR2 receptor through the intracellular kinase domain. Contrary to its agonistic effects on the TrkB receptor, 7,8-DHF was found to downregulate VEGFR2 phosphorylation both in 661W photoreceptor cells and in retinal tissue. Recent studies have identified that a flavonoid derivative, 7,8-DHF acts as a high-affinity tropomyosin related kinase receptor B (TrkB) agonist that provokes receptor dimerization and autophosphorylation and activation of downstream signalling in vivo . This coin vivo , Parkinsin vivo , Rett syin vivo , and Hunin vivo . It can in vivo . We havein vivo . TrkB isin vivo ,7. 7,8-Din vivo ,5. Our sin vivo . The Ig2etc. [The VEGF receptor super-family is another class of tyrosine kinase receptors that play a critical role in the retina. In addition to its involvement in neovascularisation associated with several proliferative disorders, abnormal VEGF expression is implicated in several ocular disease conditions such as macular edema associated with diabetic retinopathy , choroidetc. . VEGFR2 etc. ,13. Flavetc. ,15. VEGFWe report here for the first time a dual action of compound 7,8-DHF on TrkB and the VEGFR2 receptor. Using a combination of bioinformatics and biochemical approaches we have provided critical additional insights into the molecular interactions of 7,8-DHF with both the TrkB and the VEGFR2 receptor. Structurally related derivatives of 7,8-DHF are extensively compared to determine the interactions and binding parameters with the TrkB and VEGFR2 receptors. This study also illustrates the effects of 7,8-DHF treatment on the activity of VEGFR2 in both 661W photoreceptor cells as well as in the rat retina.in silico using AutoDock4.2 to reveal the best binding modes of 7,8-DHF. Our studies revealed that the binding site of TrkB-D5 comprised of Lys312, Pro313, Ala314, Leu315, Trp317, Ile323, Leu324, Glu326, Cys331, Thr332, Lys333, Ile334 and Tyr342 residues. Hydrogen bonding with Leu315 and Ile334 indicated these to be critical residues involved in interaction with 7,8-DHF  and VEGFR2 structures were subjected to 7,8-DHF binding  7,8-DHF A,B. In t protein C,D.−1 was observed to be associated with the binding of 7,8-DHF with human TrkB-D5. An inhibitory constant (Ki) of 64.79 µM was calculated for 7,8-DHF-TrkB complex binding, which correlated well with its binding energy. In general, all 37 flavonoid derivatives could be divided into two parts: scaffold I comprised of 2,3-dihydro-4H-chromen-4-one, and scaffold II formed by a 2-phenyl group (H-chromen-4-one), seven dihydroxy flavonoid derivatives through scaffold II (phenyl ring) and the remaining 16 involved interactions through both scaffold I and scaffold II with the TrkB protein   , energy n (RMSF)  and rootn (RMSF) .315 and 236 chiral (C) atom of Lys312 respectively (313 as well as atom 21 (H) of 7,8-DHF and atom 241 (O) Pro313. In addition pi–sigma interaction was also observed between the B ring of 7,8-DHF and atom 265 (C) of Leu315. Hydrogen bonding and pi–sigma bonding with the residues Pro313 and Leu315 in MD simulation may indicate a potential conformational change in TrkB (917 and atom 746 (O) of Cys917 (915 as well as atom 18 (O) of 7,8-DHF and atom 733 (H) Phe916 which was additional to that of Cys917 hydrogen bond interaction observed in molecular docking analysis    A,B. The  < 0.05) C,D. Non-Ki 64.79 µM for TrkB. The high in silicoKi suggested that 7,8-DHF did not have a significant inhibitory effect on TrkB [This study investigated the molecular interactions underlying 7,8-DHF and various other dihydroxyflavone derivatives with the TrkB receptor using a combination of molecular docking and dynamics studies. We also examined for first time molecular interactions between various flavonoid derivatives including 7,8-DHF with the VEGFR2. 7,8-DHF is an agonist of TrkB receptor and its treatment leads to upregulation in the tyrosine phosphorylation on TrkB residues and activate its downstream signalling . Intrigu on TrkB ,21 as co on TrkB ,23.in silico docking approaches based on topological surface geometry complementarities for 7,8-DHF-TrkB and 7,8-DHF-VEGFR2 complexes indicated formation of hydrogen bond networks between surface amino acid residues [et al. showed that 7,8-DHF strongly associated with the CC2 domain and also partially interacted with the leucine-rich motif domain. This additional binding site at Ig2 may play a role in stabilising or further enhancing the 7,8-DHF binding to the TrkB. Similar involvement of the TrkB Ig2 domain in interactions with BDNF were observed with potential contributions to the TrkB receptor dimerization [N-glycosylation site in the Ig2 domain could also play a role in ligand receptor interaction, but further studies are required to establish this [The residues . The staresidues . Moleculrization . The N-gpi–sigma bonds. The 7,8-DHF-VEGFR2 complex also showed formation of two hydrogen bonds with Cys917 after molecular docking. Molecular simulations further showed additional 5 H-bonds involving Glu915, Phe916 and Cys917 residues. Detection of additional bonds and interactions following molecular simulations indicated that the protein-ligand complexes acclimatize and achieve a more stable configuration over a period of time. No significant changes were observed in the total energy of either of the protein-ligand complexes within the 10ns simulation period indicating that the complexes attained a stable conformation , serine/threonine-protein kinase 4 (STK4), phosphatidylinositol 4,5-bisphosphate 3-kinase (PK3CG) and CUB domain-containing protein 1 (CDCP1) (568 (TrkB) which corresponds to Val846 (VEGFR2) is buried in the TrkB structure and is not surface accessible for development of bond formation. These observations suggested that the absence of these structural motifs in TrkB could be the reason underlying exclusion of 7,8-DHF interactions with the ATP binding site of TrkB in contrast to that observed in VEGFR2  A. Furthen VEGFR2 . Togethein silico studies was investigated in the photoreceptor 661W cells in culture as well as in the rat retina under in vivo conditions. 7,8-DHF treatment has been shown to activate the TrkB signalling and reduce apoptosis by activating the downstream processes of Akt and Erk1/2 pathways. We chose 661W cells as these have been shown to express VEGFR2 [in silico predictions. Briefly, the fact that similar inhibitory effect was observed in the rat retinal tissues upon 7,8-DHF treatment validate our 661W results and reassure that the inhibitory effects are not an experimental artefact or not a cell specific phenomenon. The loss in VEGFR2 activity can potentially be attributed to 7,8-DHF interactions with key active site residues Glu915, Phe916, and Cys917 that may give rise to conformational changes in the geometry of the protein as observed in the molecular dynamic studies  and anti-TrkB (sc20542) antibodies were obtained from Santa Cruz Biotechnology . Anti-VEGF antibody  and VEGFR2 antibody  were also used for western blotting. β-Actin antibody was obtained from Sigma, USA. All other reagents were of analytical grade from Sigma .Animal experiments were conducted in accordance with the Australian code of practice for the care and use of animals for scientific purposes and the guidelines of the Association for Research in Vision and Ophthalmology (ARVO) statement for the use of animals in ophthalmic and vision research and were approved by the Macquarie University Animal Ethics Committee (2012/31), NSW, Australia. Male Sprague-Dawley rats were obtained from Animal Research Centre, Perth, Australia and maintained in the animal house in cyclic light , in an air-conditioned room with controlled temperature (21 ± 2 °C) and with free access to water and rodent chow.et al., San Francisco, CA, USA), implying amber parameters, followed by minimization with MMTK method in 500 steps with a step size of 0.02 Å [Crystal structure of the TrkB-D5 domain bound to Neurotrophin-4/5 (PDB id: 1HCF)  and VEGFf 0.02 Å . The actf 0.02 Å  for the The three-dimensional (3D) structures of dihydroxy flavones derivatives were collected from the pubchem database . In totahttp://www.pdb.org/). Rigid docking was performed for studying protein–ligand interactions through AutoDock tools. The atom types and bond types were assigned [Ki) were used for determination of binding energies of different docking conformations, ranking in accordance to their binding scores [Ki, binding free energy, electrostatic energy, van der Waals, hydrogen bond, desolvation energy, total intermolecular and torsional energy for 37 DHF derivatives are given in + software  [The docking of the 37 dihydroxy derivatives to the binding site of TrkB-D5 and VEGFR2 was performed using the AutoDock 4.2    were use+ and Cl− to balance the net charge of the system. In Desmond, equilibration of the whole system was carried out using default protocol made up of a series of restrained minimizations and MD simulations. During simulation, initial coordinates of the protein molecules were slowly relaxed without deviation. The minimized system was relaxed with NPT  ensemble restraining non-hydrogen solute atom for 10 ns simulation time. The full system was composed of 17,346 atoms for TrkB-D5 and 36,979 for VEGFR2 complex respectively. The temperature was maintained at 300 K and pressure at 1.01325 bars. Long-range electrostatic interactions were computed using particle-mesh Ewald method [MD simulations were performed for the complex of 7,8-DHF-TrkB and 7,8-DHF-VEGFR2 using Desmond 3.2 software  , incorpod method ,48 and v2. Approximately, 2.0 × 105 cells were seeded in each culture dish 6–12 h before treatment [in vivo experiments, 7,8-DHF (2 mg/kg) was administered intraperitoneally to the rats. The rat retinas were harvested, flash frozen and sonicated in the lysis buffer for further analysis.Photoreceptor derived 661W cells were maintained in DMEM culture media containing 10% fetal bovine serum and 1% penicillin/streptomycin at 37 °C at 5% COreatment ,50. Cell3, 100 mM NaF, 1 mM Na2MoO4, 10 mM Na4P2O7). The proteins were separated by 10% SDS-PAGE and transferred to PVDF membranes as explained previously [661W cells and retinal tissues were lysed in lysis buffer  containing  and . All values with error bars are presented as mean ± SD from given n sizes and compared by Student’s in vivo study where 7,8-DHF administration led to a decrease in the activity of VEGFR2 in the retina. The combined in silico, cell culture and in vivo studies suggest emergence of 7,8-DHF as a dual action compound, which in addition to its known agonistic effects on TrkB receptor, can suppress the VEGFR2 activity.Inhibition of VEGF/VEGFR signalling may be critical in several disorders involving unregulated angiogenesis. A poorly monitored treatment, on the other hand, may give rise to unwarranted complications. In the context of retina for example, excess anti-VEGF treatment may cause onset of dry AMD leading to gradual neurodegeneration. In contrast, activation of the neurotrophic factor signalling such as TrkB may play a critical role in protecting against several neurodegenerative disorders including retinal disorders. In this study, we have evaluated the potential of flavonoid derivatives to act as VEGFR2 inhibitors and the same time evaluated their potential as an activator of neurotrophic factor signalling via activation of the TrkB receptor, with emphasis on examining additional interactions with 7,8-DHF. The interactions of 7,8-DHF and several of its derivatives with the extracellular domain of TrkB receptor using a combination of molecular docking and dynamics tools were determined and presented here. Potential interactions of 7,8-DHF and its derivatives with VEGFR2 were also evaluated. Computational studies indicated 7,8-DHF to be an inhibitor of the VEGFR2. Effects of 7,8-DHF on photoreceptor cells in culture revealed that 7,8-DHF downregulated the VEGFR2 activity. Similar results were obtained in the


A density functional theory calculation shows that covalent bonds were formed between the R6G molecules and the defect sites on the graphene nanosheets. Our study reveals the important role that defects play in tailoring the properties and sensor device applications of graphene materials.A proper understanding of the role that molecular doping plays is essential to research on the modulation of the optical and electronic properties of graphene. The adsorption of R6G molecules onto defect-rich reduced graphene oxide nanosheets results in a shift of the Fermi energy and, consequently, a variation in the optical constants. This optical variation in the graphene nanosheets is used to develop an ultrasensitive surface plasmon resonance biosensor with a detection limit of 10 The application of graphene in next-generation electronics and renewable energy devices has been hindered by the absence of a band gap and the fact that the material presents challenges to optical modulation12451114−1710−11 M and an LOD of 10 aM. The success of modulating the ERGO optical properties for use as a sensitive layer in ultra-sensitive sensing will open new pathways for designing more efficient sensors in the near future.Surface plasmon resonance (SPR) has been employed to monitor biomolecular binding events via the detection of dielectric constant changes on the surface of a thin gold chip161719205 Ha, and a maximum force of 0.002 Ha/Å and maximum displacement of 0.005 Å are adopted in the geometry optimization. Smearing techniques are used to achieve self-consistent field convergence with a smearing value of 0.005 Ha. The graphene sheet is represented using a hexagonal supercell containing 200 atoms with a p (10×10) structure in the x-y plane and a vacuum layer of 35 Å along the z direction between the sheets, which leads to negligible interaction between the periodic image2425The geometric and energetic calculations are performed using the spin unrestricted DFT, as implemented in the Dmol3 codeTwo dimensional GO nanosheets are self-assembled on a flat Au surface by utilizing the strong metal-carbon coupling between the GO and the Au surface. Cyclic voltammetry is then used to electrochemically reduce the GO nanosheets on the Au surface. The details and characterizations are described in our previous reports20SPR spectrometry was carried out using a TR2005 spectrometer . The set-up was based on the conventional Kretchmann configuration and included a He-Ne laser with a wavelength of λ = 632.8 nm coupled to the system via a high refractive index prism, LAFSN9 glass ε = 3.40. The Gold-coated sensor chip mounted was with a homemade electrochemical flow cell and attached to the prism base with high index matching oil . The reflected light was detected using a photodiode.DLD.UPS and XPS were carried out with an unfiltered He I (21.2 eV) gas discharge lamp and a hemispherical analyser using a Kratos AXIS UltraThe Raman spectra of the R6G molecules were obtained from the ERGO, Graphene, and GO substrates using an excitation wavelength of 514 nm under normal incident light with a Renishaw 1000 microspectrometer connected to a Leica microscope with an objective lens of 50 × (NA = 0.5). The typical accumulation time was 10 s.The SPR responses to R6G on different graphene materials are shown in 20−17 M to 10−11 M. It is clear that the SPR response for the R6G on the ERGO is much higher than for the other substrates. On a conventional Au film SPR chip, the changes in the SPR responses are barely detectable for the same series of concentrations, indicating the essential role that the surface modifications play. It is worth noting that the response from 10−11 M R6G on the ERGO surface is of 35 mRU, which is seven times higher than that for the GO and graphene substrates. This suggests that ERGO is a good sensitive layer for an SPR sensing platform. The ERGO sensitive layer displays the lowest LOD at 10–17 M estimated according to the IUPAC guideline of 3:1 signal to noise. However, defect-free graphene and GO exhibit poor sensing performances at low concentrations. ERGO is highly defect-rich due to the removal of oxygen functional groups in the GO by electrochemical reductionThe calibration curves for the SPR response versus the R6G concentration are shown in −6 M, a monolayer of R6G molecules was proven to adsorb onto an Au film and the ERGO after a 30 min incubation period and thorough rinsing88The enhancement of the SPR signal from the doping effect is confirmed by a control experiment using a monolayer of R6G molecules on Au and ERGO substrates. The SPR angle shift on the ERGO surface is 400 mdeg, which is more than two times greater than that observed on the Au film, as shown in A relationship between the dielectric constants and the Fermi level of the intrinsic graphene is established using the Kubo formula and the local Random Phase Approximation (RPA)31f is the Fermi-Dirac distribution function. The first term of this equation describes the intraband contribution, whereas the second term denotes the interband transition to generate the electron-hole pair. The Kubo formula has been verified to accurately describe the complex dielectric constant of graphene in the optical regime with corrections of a few percentwhere σ is the conductivity of the graphene, The effective dielectric constant −1 is usually assigned to the E2g phonon of the C sp2 atoms, the D peak at ~ 1347 cm−1 is a breathing mode of κ-point phonons of A1g symmetry, the 2D band at ~ 2700 cm−1 is due to a double resonance process, and combinational modes in the D + G band exist at 2938 cm−1 21. The D peak is visible in −1. The observed Raman bands are assigned to the R6G molecules. The Fermi energy from the doping carrier concentration is obtained from the experiential formulaThe use of Raman spectra confirms the change of the Fermi energy during doping, as shown in where n is the doping concentration, Egap is the band gap of the ERGO induced by molecular doping, and −1 is a breathing mode of κ-point phonons of A1g symmetry, and the 2D band at ∼2700 cm−1 is due to a double-resonance process. And the D-band is often used to measure the disorder of the graphite materials. The D peak is visible in where −1 observed in the Raman spectra in Ultraviolet photoelectron spectroscopy (UPS) is also used to investigate the electronic structures of the graphene-based materials before and after incubation using R6G molecules. The secondary-electron onset representing the vacuum levels of the samples is used to determine the work function obtained from the UPS38To understand the mechanism by which a R6G molecule adsorbs on defect-rich graphene, theoretical calculations have been performed using the density functional theory (DFT). We start with a hexagonal graphene supercell (10 × 10 graphene unit cell) containing a C vacancy as a simple model, as shown in Fig. 6aThe presence of R6G dopants lead to significant changes in the electronic structures of graphene with vacancies. For the density of states (DOS), as shown in 44−17−10−11 M and an LOD of 10 aM. The existence of defect in the graphene nanosheets result in abundant dangling bonds, which are beneficial for the formation of covalent bonds with R6G molecules. This works as not only a new mechanism for SPR sensing but also a new method for the modulation of the optical properties of graphene-based materials.In summary, the concept of an SPR sensor with ultra-high sensitivity, via a sensitive layer with defect-rich graphene, offers numerous opportunities to develop new biological and chemical sensors and sensing strategies. The defect-rich graphene tunable energy band is presumed to serve as a signal amplifying sensing layer on the Au surface to provide an ultralow limit of detection and a long-term stability. The results show that when small amounts of dye molecules are adsorbed on the defect-rich electrochemically reduced graphene oxide (ERGO) surface, the increase in the dielectric constant of the ERGO results in significant changes to the SPR spectrum. The detection of the target R6G molecule provides a linear dynamic range of 10How to cite this article: Xue, T. et al. R6G molecule induced modulation of the optical properties of reduced graphene oxide nanosheets for use in ultrasensitive SPR sensing. Sci. Rep.6, 21254; doi: 10.1038/srep21254 (2016).


This paper reports a highly reliable transparent conductive electrode (TCE) that integrates silver nanowires (AgNWs) and high-quality graphene as a protecting layer. Graphene with minimized defects and large graphene domains has been successfully obtained through a facile two-step growth approach. Ultraviolet light emitting diodes (UV-LEDs) were fabricated with AgNWs or hybrid electrodes where AgNWs were combined with two-step grown graphene (A-2GE) or conventional one-step grown graphene (A-1GE). The device performance and reliability of the UV-LEDs with three different electrodes were compared. The A-2GE offered high figure of merit owing to the excellent UV transmittance and reduced sheet resistance. As a consequence, the UV-LEDs made with A-2GE demonstrated reduced forward voltage, enhanced electroluminescence (EL) intensity, and alleviated efficiency droop. The effects of joule heating and UV light illumination on the electrode stability were also studied. The present findings prove superior performance of the A-2GE under high current injection and continuous operation of UV LED, compared to other electrodes. From our observation, the A-2GE would be a reliable TCE for high power UV-LEDs. The two-step growth is highly effective in reducing the point defects and increasing the graphene domain size, both factors benefit the graphene to be used as conformal layer to protect the AgNWs from oxidation. Herein, one-dimensional AgNWs network is integrated to graphene synthesized by two-step growth method without any considerable loss in optical transmittance to fabricate exceptionally stable and conductive TCEs. As a proof of concept, we demonstrate operation of a 380 nm UV-LED using this hybrid electrode and compare the performance and long-term reliability with AgNWs only electrode and similar hybrid electrode comprising of AgNWs and conventional one-step grown graphene.2, respectively. The corresponding nucleation densities are calculated to be 2.77 × 106/cm2 and 5.21 × 105/cm2, respectively. Raman spectra were acquired on each graphene films to examine the crystal quality, as shown in −1 and 2685 cm−1, respectively. Raman spectra recorded from both samples reveal typical characteristic of monolayer graphene, i.e. a single Lorentzian peak with a full width at half maximum of 28 cm−1 and the 2D to G intensity ratio greater than 2. Moreover, the so-called defects or disorder-provoked D-band peak around 1350 cm−1 is negligible, implying that both graphene layers are high quality with minimized defects. Though Raman analysis evaluate the defect distribution and quality of graphene by the D band intensity, it is difficult to detect accurately the low-density defects that unroll across over large area. To give a further insight into structural quality of graphene on large scale, the film-induced frustrated etching (FIFE) test is performed. Commercial copper etchant, ammonium persulfate [(NH4)2S2O8], is dropped on to graphene grown on Cu foils. After 10 sec, the dropped etchant is rinsed with deionized water and then the surfaces of one-step and two-step graphene on Cu foils are probed by atomic force microscope (AFM), as shown in 7 cm−2 and 2 × 106 cm−2, signifying that the etch-pit density in two-step graphene is about one order less due to the decrease of the amount of graphene grain boundaries. The reduction of grain boundaries is a result of minimization of nucleation density of graphene during the first growth step and associated decrease in defects caused by better stitching between domain boundaries by fast lateral growth during the second step. To confirm the barrier properties of graphene, the oxygen transmission rate (OTR) measurement is carried out after the graphene films being transferred to poly ethylene terephthalate (PET). The values of OTR for bare PET and PET substrates cover by one-step graphene (1-G/PET) and two-step graphene (2-G/PET) are measured to be 20.89 ± 0.4, 12.52 ± 1.2, 5.39 ± 0.9 cc/m2-day, respectively. The 2-G/PET exhibits the lowest OTR value, which is 74% less than that of bare PEF owing to the impermeability of graphene with the minimized defect density and large graphene domain. It is evident that graphene plays an important role as gas barrier against oxygen.In the growth of graphene by CVD, the initial stage of growth is a key to obtain large domain size and good crystal quality. TC) of the three different TCEs are depicted in TC = T10/Rshsh) and transmittance measured at 380 nm. The transmittance of the AgNWs, A-1GE, and A-2GE at 380 nm is measured to be 91.5%, 93%, and 93%, respectively. Generally, some loss in optical transmittance could occur in hybrid TCEs due to the additional absorption by graphene in the visible wavelength region. Conversely, the transmittances of A-1GE and A-2GE at 380 nm are increased about 1.5% compared to the transmittance of AgNWs (91.5%), which is a likely result of partial screening of plasmon absorption of AgNWs. This is because the dielectric environment of the AgNWs is interrupted by the graphene, which inhibits the collective oscillation of free electrons in AgNWs arising due to interacting electromagnetic field26,28TC due to the reduced sheet resistance and increase in transmittance at 380 nm, as shown in Optical transparency and sheet resistance are the two important criterias that must be considered for the use of TCEs in LEDs, because the efficiency of the LEDs largely associated with these two parameters. The transmittance, sheet resistance, and figure of merit  intensity is enhanced for the LED with A-2GE in comparison to LEDs made with AgNWs or A-1GE, as shown in p-electrode for the LED with AgNWs due to insufficient current spreading by the formation of loosely bound random networks of AgNWs. Of particular point of interest is that a blue LED fabricated with similar AgNWs only electrode offered well-distributed current over the whole emission area, as shown in p-GaN/p-AlGaN layers in the former, and hence it will have an additional influence on current spreading and light output. However, recent studies demonstrated uniform light emission over the entire area of an UV-LED with the application of AgNWs TCE12max-EQE)/EQEmax is found to be 72%, 55.8%, and 47% for UV-LEDs with AgNWs, A-1GE, and A-2GE, respectively, at an injection current of 100 mA. The primary reasons for the reduced efficiency droop associated with the use of A-2GE are decrease in the heating effect caused by the reduced series resistance and improved current spreading30The performances of AgNWs, A-1GE, and A-2GE as TCEs in UV LEDs of 380 nm emission wavelength are evaluated. For practical application of TCE, it is important to take into account the long-term stability and reliability of TCE material. Herein, we intend to compare the performance of all the three devices after one month. Meanwhile, studies have shown that moderate UV exposure could lead to degradation of the performance of AgNWs32In summary, the impact of the graphene quality on the performance of a hybrid electrode of graphene on Ag NWs in GaN-based UV light-emitting diodes has been studied. Two dissimilar graphene films grown by one-step and two-step approaches were evaluated as a protective transparent conductive coating to Ag NWs towards the fabrication of extremely stable TCEs for UV-LEDs. The hybrid electrode using two-step graphene showed good ambient stability with stable sheet resistance over time. The UV LED using this TCE offered a low forward voltage, an increase in the EL intensity, and a reduction of efficiency droop. Furthermore, the device exhibited stable light emission even at high injection currents while the Ag NWs only electrode degraded over time. Our findings suggest that high-quality graphene on Ag NWs as hybrid TCE has great potential in high-power devices owing to its stability and reliability.The AgNWs used in this work was purchased from NANOPYXIS Corp. and diluted to a concentration of 5 mg/ml before being used. The diluted aqueous dispersion was then spin-coated on to desired substrates at 1000 rpm for 40 seconds to form the transparent electrodes.2 flow rate of 15 standard cubic centimeters per minute (sccm) by split-tube furnace. Concurrently, the CVD chamber was pumped down to 0.072 Torr. Then, the Cu foil was annealed for 50 min. In the one-step growth, graphene synthesis was carried out under flowing CH4 of 13 sccm and H2 of 15 sccm at 1030 °C for 23 min. In the case of two-step growth, large size graphene domains were initially achieved on Cu foils by reducing the nucleation sites in a mixed CH4/H2 (5 sccm/100 sccm) ambient for 1 min at 1030 °C. In the second step, continuous graphene was obtained when the flow rate of CH4 and growth time were increased to 13 sccm and 8 min, respectively, while maintaining the H2 flow rate and temperature constant. Finally, the chamber was cooled down to room temperature by injecting 500 sccm of Ar. Polymethyl methacrylate (PMMA) was spin-coated onto graphene surface at 4200 rpm for 50 s to make a supporting layer for the graphene during the transfer to other substrates of interest. Thereafter, the Cu foil with PMMA-spun graphene was immersed in 0.1M Ammonium Persulfate [(NH4)2S2O8] solution for 4 h to remove the Cu foil. PMMA/graphene layer was transferred to AgNWs-coated substrates in order to form the hybrid electrode. Finally, the PMMA was removed by using acetone. More details on the growth of graphene and transfer can be found in ref. We prepared three different TCEs as follows: (1) a bare AgNWs electrode, (2) a hybrid electrode of AgNWs-graphene synthesized by conventional one-step growth (A-1GE) and (3) a hybrid electrode of AgNWs-graphene synthesized by two-step growth (A-2GE). Firstly, an aqueous solution containing AgNWs was spin-coated on substrates of interest at 1000 rpm for 40 s, which is the optimum condition in terms of transmittance-sheet resistance tradeoff and more details can be found in ref. n-type GaN layer, five-pairs of In0.04Ga0.96N/Al0.08Ga0.02N MQWs, a Mg-doped p-Al0.25Ga0.75N electron blocking layer, and a p-type GaN cladding layer. Briefly, the Si-doped n-GaN layer of 2-μm was grown on un-doped GaN layer at 1100 °C under a pressure of 400 mbar for 60 min by metal organic chemical vapor deposition (MOCVD). Subsequently, five pairs of InGaN quantum wells and GaN barrier layers of thickness 3 nm and 12 nm, respectively, were grown at 790 °C and 810 °C, to form the active region. Then, a 25 nm-thick Mg-doped p-Al0.25Ga0.75N electron blocking layer and a 100 nm-thick p-GaN contact layer were grown at 1040 °C. Following the growth of LED epi-wafer, discrete LED devices were fabricated with a chip size of 350 × 350 μm2 in which the mesa region was defined by an inductively coupled plasma reactive ion etching system using Cl2/BCl3 gases until n-GaN layer was revealed for n-electrode contact. Subsequently, different TCEs were formed on p-GaN layer as explained in the previous section. As a final step, Cr (50 nm)/Au (250 nm) metals for the n- and the p-electrode were deposited onto both the transparent electrode and the n-GaN layer using electron beam evaporator.The UV LED structure used in this study is composed of an un-doped GaN layer, a Si-doped Field emission scanning electron microscopy  was used to probe the surface morphology of the samples investigated in this work. Optical transmittance and sheet resistance measurements were performed on a UV/VIS spectrometer (V-670EX) and a four-point probe system (CMT-SR1000N), respectively. The surface topography of graphene on Cu after the film-induced frustrated etching (FIFE) test was probed by atomic force microscope  in tapping mode. The quality of graphene was characterized by Raman spectroscopy using 514 nm-line of an Ar ion laser as an excitation source. Current-Voltage (I–V) and electroluminescence (EL) measurements on the LED devices were performed using a probe station system. The oxygen transmission rate (OTR) was analyzed by a commercial MOCON instrument.How to cite this article: Seo, T. H. et al. The role of graphene formed on silver nanowire transparent conductive electrode in ultra-violet light emitting diodes. Sci. Rep.6, 29464; doi: 10.1038/srep29464 (2016).


Understanding the processes that influence the structure of biotic communities is one of the major ecological topics, and both stochastic and deterministic processes are expected to be at work simultaneously in most communities. Here, we investigated the vertical distribution patterns of bacterial communities in a 10-m-long soil core taken within permafrost of the Qinghai-Tibet Plateau. To get a better understanding of the forces that govern these patterns, we examined the diversity and structure of bacterial communities, and the change in community composition along the vertical distance  from both taxonomic and phylogenetic perspectives. Measures of taxonomic and phylogenetic beta diversity revealed that bacterial community composition changed continuously along the soil core, and showed a vertical distance-decay relationship. Multiple stepwise regression analysis suggested that bacterial alpha diversity and phylogenetic structure were strongly correlated with soil conductivity and pH but weakly correlated with depth. There was evidence that deterministic and stochastic processes collectively drived bacterial vertically-structured pattern. Bacterial communities in five soil horizons (two originated from the active layer and three from permafrost) of the permafrost core were phylogenetically random, indicator of stochastic processes. However, we found a stronger effect of deterministic processes related to soil pH, conductivity, and organic carbon content that were structuring the bacterial communities. We therefore conclude that the vertical distribution of bacterial communities was governed primarily by deterministic ecological selection, although stochastic processes were also at work. Furthermore, the strong impact of environmental conditions  on these communities underlines the sensitivity of permafrost microorganisms to climate change and potentially subsequent permafrost thaw. Furthermore, Faith’s PD [Chao1-richness was computed to estimate the community diversity using the MOTHUR program . Chao1-rith’s PD  was calcP < 0.05 or P > 0.95). For a single community, a significantly positive or negative NTI value indicated that co-occurring species were more closely or distantly related than expected by chance. Based on the hypothesis that closely related taxa were more ecologically or functionally similar (phylogenetic niche conservatism), the obtained NTI measure can be used to infer ecologically similar (phylogenetic clustering) or ecologically dissimilar (phylogenetic overdispersion) taxa within a given community [To characterize phylogenetic community structure within each sample, we calculated the mean nearest taxon distance (MNTD) . A randoommunity . A mean ommunity . To corrTo examine the beta diversity patterns of bacterial communities, the Bray-Curtis metric was computed to describe the dissimilarity in species community composition (taxonomic beta diversity) between all pairwise comparisons of bacterial communities . PhylogeTo estimate the relative importance of deterministic and stochastic processes on bacterial distributions, variation partitioning was performed for taxonomic and phylogenetic beta diversity. We partitioned beta diversity into spatial and environmental components using both the distance-based approach and the raw data approach as previously described ,15,24, ar = 0.769, P < 0.001) and conductivity  increase significantly with depth. No observable correlations were found between the other variables and depth.Our soil samples were collected from different depth intervals within a 10-m-long permafrost core, which progresses from surface active layer soil into a layer of permafrost soil. The stratigraphic profile and soil physicochemical characteristics across depths are shown in The soil characteristics at the very bottom of the permafrost core (9.75 m) were completely different from those of the other soil horizons . This hoNothing was recovered from the negative parallel controls, suggesting that contamination was not introduced during extraction and purification processes. To yield enough DNA for PCR amplification and minimize individual extraction biases, DNA extractions from three replicate subsamples were combined for each sampling depth and used as one sample for the construction of clone library also see . A totalAlphaproteobacteria and Actinobacteria, which showed the highest diversity, consisting of 46 phylotypes, respectively. Sequences related to Betaproteobacteria, Gammaproteobacteria, Firmicutes, Acidobacteria and Bacteroidetes were also frequently detected. In addition, phylotypes of Deltaproteobacteria, Gemmatimonadetes, Planctomycetes, Verrucomicrobia, Saccharibacteria (former candidate division TM7), Armatimonadetes (former candidate division OP10), Cyanobacteria, Chloroflexi, and Nitrospirae were identified at relatively low diversity, as well as members of an unclassified phylum , while the pure effect of environmental distance was significant for all metrics after controlling for spatial distance . These results suggest that bacterial communities in 11 soil horizons were phylogenetically clustered and the other five communities were phylogenetically random, whereas there was an average trend towards clustering across all communities.The analysis of phylogenetic structure revealed the phylogenetic patterns of bacterial communities through the permafrost core profile. The MNTD of 11 bacterial communities was significantly different from the null communities , whereas it was not significantly different from the null communities  in the other five communities, of which two (at depths of 150 and 225 cm) originated from the active layer and three  from permafrost . All theP = 0.006) than the pure effect of space (depth) . When the distance-based method was employed, variation partitioning showed that the pure environmental distance explained 9.53% and 22.91% of the variation in taxonomic dissimilarity and betaMNTD, respectively, while the pure spatial distances explained less than 0.32% for the both metrics ; of which, the soil conductivity  was the most significant variable  was the most relevant variable, followed by the soil conductivity .The dissimilarity in species community composition of bacteria was significantly related with conductivity, C/N ratio, SOC, pH and TN  [Upon observing significant vertical structure we evaluated whether the vertical patterns of the sampled bacterial communities were governed primarily by deterministic or stochastic processes. Analyses of phylogenetic structure can complement analyses of taxonomic structure, potentially providing additional insights into the factors that shape local communities ,47. Our clusion)  as well clusion) . HoweverOn the other hand, we observed that 5 of 16 bacterial communities were phylogenetically random, which suggested that the bacterial community assembly in these soil horizons of the permafrost core was mainly determined by stochastic processes. According to neutral theory , these rAlthough the main aim of this study was not to examine the specific environmental factors that determine the biodiversity patterns, our results do suggest that they show potential in affecting the bacterial alpha diversity, phylogenetic structure, and spatial turnover across the permafrost core. Multiple stepwise regression analysis revealed that soil conductivity and pH were the most important explanatory variables for bacterial alpha diversity and phylogenetic structure, respectively. The change in taxonomic and phylogenetic community composition was significantly correlated with most measured soil variables, especially the soil conductivity and organic carbon content. These results accord with many previous findings, emphasizing the importance of pH in explaining phylogenetic structures of lacustrine bacterioplankton communities , as wellIn conclusion, our study reveals the vertically-structured patterns of bacterial communities and infers the ecological processes driving these patterns in a permafrost core. We observed that the bacterial communities were not randomly distributed along the soil core, but rather showed a vertical distance-decay relationship. The vertical distribution of bacterial communities was mainly driven by deterministic processes such that the observed distance-decay relationship was most likely the result of physicochemical environmental conditions , although stochastic processes were also involved. Our findings highlight the importance of considering information on both the taxonomic and phylogenetic structure of microbial communities and of using multiple lines of evidence to carefully evaluate whether distance-decay relationships indicate a strong influence of deterministic or stochastic processes. Our study further contributes to the emerging body of literature aimed at understanding the microbial ecology of permafrost , a key rS1 FigBootstrap values above 50% are shown as a percentage of 1000 replicates. The scale represents the number of mutations per nucleotide position. Numbers in parenthesis represent the number of phylotypes and orders assigned to each division respectively.(TIF)Click here for additional data file.S2 FigSolid lines represent linear regressions and the significance levels are determined by Mantel test (9999 permutations).(TIF)Click here for additional data file.


Graphene grown by high temperature molecular beam epitaxy on hexagonal boron nitride (hBN) forms continuous domains with dimensions of order 20 μm, and exhibits moiré patterns with large periodicities, up to ~30 nm, indicating that the layers are highly strained. Topological defects in the moiré patterns are observed and attributed to the relaxation of graphene islands which nucleate at different sites and subsequently coalesce. In addition, cracks are formed leading to strain relaxation, highly anisotropic strain fields, and abrupt boundaries between regions with different moiré periods. These cracks can also be formed by modification of the layers with a local probe resulting in the contraction and physical displacement of graphene layers. The Raman spectra of regions with a large moiré period reveal split and shifted G and 2D peaks confirming the presence of strain. Our work demonstrates a new approach to the growth of epitaxial graphene and a means of generating and modifying strain in graphene. The introduction of strain provides a route to modify both the electronic properties and phonon spectrum of graphene monolayers1234678910111231516et al.31333637Growth by MBE is realised through the direct sublimation of one or more source materials, in this case carbon, onto a substrate surface and allows independent control of growth temperature and deposition rate. MBE is widely used to grow conventional semiconductor device-grade materials, particularly those which incorporate heterojunctions, but has so far had little impact on the growth of graphene. For this relatively new material chemical vapour deposition (CVD) is much more widely used19212312272829We have grown graphene by MBE on hBN flakes which are exfoliated from high-temperature high-pressure grown bulk hBN crystals31et al.The regions between these aggregates, which have typical separation of ~1 μm, have a uniform contrast in et al.120, is reported to be in the range 13.9–15 nm which is consistent with the value, 13.9 nm, expected for unstrained graphene  (Δλ/λs). For the values observed in The period of the hexagonal array in In other areas of the flake . This peak is present in all spectra with a near-constant energy but strong variation in amplitude, reflecting the inhomogeneous distribution of aggregates on the surface. The position of the red-shifted peaks shows a monotonic variation with λs, strongly supporting the hypothesis that the graphene is strained; this has not been observed in previous reports of exfoliated or CVD graphene on hBN1229The presence of strain is also expected to influence the Raman spectrum of the graphene and we have acquired a full two-dimensional Raman map of the flake in −1 and 1615 cm−1 close to the expected values for graphene. However, we also observe a shoulder on the low energy side of the G peak which evolves into a more distinct feature which can be decomposed into two broad peaks centred on 1553 and 1527 cm−1 for λs = 26.3 nm. Other peaks present in the spectrum but not shown in −1. These peaks are therefore associated, at least partially, with the presence of carbon aggregates.As shown in s ~ 14 nm (green) and the red-shifted components for λs ~ 26 nm (red)); the false colour map in To generate a Raman map we fit the 2D region of the measured spectrum at each point to the red, green and blue spectra shown in the inset to max/λmin−1) where λmax/min are the maximum/minimum periods extracted locally; note that g = 0 for a non-distorted moiré pattern). These data, plotted in In −1/% strain and −86 ± 6 cm−1/% strain. In addition, we observe a small shift even for Δλ = 0. It has previously been shown experimentally−1/%. The dependence of the red-shifted G peak is more difficult to determine from our data since the peaks are rather broad. Assuming a linear dependence on strain (see SI) we find a red-shift dependence of −37 cm −1/% and −28 cm−1/% for the two additional components. However, from symmetry considerations we would not expect either the G or the 2D peaks of a freestanding graphene layer to be split for isotropic strain. We speculate that the split peak is due to interactions with the hBN substrate, for example a difference in local environment of carbon atoms in analogy with the formation of 2D1 and 2D2 features in graphiteWe also extract the dependence of the 2D peak positions on percentage strain, determined from the moiré period as discussed above see . SpecifiIn As the carbon dosage is increased  we see aWe have confirmed that the cracks, such as in g, and hBN, ∝BN. A tensile strain of ~1%, as observed here, implies that (∝g–∝BN), averaged over the relevant temperature range (300–1770 K) is positive with a value 8 × 10−6/K. The coefficient for hBN  is −3 × 10−6/K at 300 K and remains negative, but with reduced magnitudeg; Bao et al.g is negative at 300 K, but then increases to a positive value for a temperature, T > 350 K, while Yoon et al.et al. argued that ∝g is positive over all measured temperatures in agreement with theoretical predictionsg–∝BN) ~3 × 10−6/K. This is lower than the average quoted above, but we emphasise that data are not available between 800 K and the growth temperature, 1770 K, and, given the uncertainty related to these quantities, thermally-induced strain is a plausible origin for the observed effects.We propose that the strain in the graphene layer is introduced during post-growth cooling and is maintained by a quasi-random distribution of nucleation sites which act to pin the material. The simplest explanation for the origin of the strain is a difference between the thermal coefficients of expansion of graphene, ∝o; in fact we would not expect a bright dislocation edge to be formed parallel, and close to, a free boundary since the mismatch in lattice constants which occurs in these regions must be stabilised by compressive stress arising from the lattice-matched graphene on each side of the dislocation. This implies a complex evolution of the dislocation network due to finite size effects as the island continues to grow and a possible activated process for the introduction of new dislocation lines. Note that the introduction/elimination of a dislocation parallel to an island edge generates an advancement/retraction of the edge and therefore modifies the overall strain in the island. It is possible that thermally activated fluctuating displacements of the islands edge occur until neighbouring islands coalesce thus stabilising a strained configuration.Graphene grown by CVD on hBN does not exhibit the large moiré pattern reported here and one possible reason for this difference is the pinning role of the nucleation sites in MBE growth; these aggregates are not observed in CVD growth. There are other differences, for example the growing edge of graphene is likely terminated by hydrogen in CVD growthOur results demonstrate, for the first time, that MBE can be used to grow large areas of aligned graphene and also, unexpectedly, that the resulting material can be highly strained. Moreover, the strain, and physical properties of the graphene, can be modified through the generation of cracks using the probe of an AFM. This also leads to a physical displacement of the edges of graphene domains so the AFM actuates a nanoscale relative displacement of the grown layer, and, furthermore, gives rise to highly parallel edges which appear regular on a nanometre scale. The strongly anisotropic deformation close to a crack indicates the possibility of better controlled routes towards the engineering of more complex strain fields in graphene, for example through the lithographic formation of arrays of etched holes, or the formation of artificial pinning sites on hBN through nanofabrication prior to growth. Our work motivates further exploration of MBE growth as a route to the controlled introduction of strain into graphene layers for the generation of pseudomagnetic fields of order 10 T, novel electronic structure and new device paradigms.−10  Torr) supplied by Veeco which is modified to reach growth temperatures of 1850 °C and is compatible with substrates up to 3 inches in diameter. In this system the substrates are mounted in a vertical configuration with the substrate heater mounted above the substrate. To deposit carbon we use a SUKO-63 sublimation source, essentially a high purity pyrolytic graphite filament which is Joule heated, supplied commercially by Dr. Eberl (MBE-Komponenten GmbH). As substrates we use exfoliated flakes of hBN from high-temperature high-pressure grown bulk hBN crystals2 double sided polished sapphire (0001) substrates (SurfaceNet GmbH) and cleaned by immersion in toluene  overnight and heating at 400 °C for eight hours in a flow of 0.15 sl/min of Ar/H2 (95:5). The substrates are loaded on a Ta holder and following entry to the MBE system are pre-annealed at 400 °C for 0.5 hour prior to growth. Due to the use of the transparent sapphire substrate, pyrometer measurements give a reading only of the heater temperature. Instead we estimate the substrate temperature during growth using a thermocouple mounted in the substrate heater. The carbon deposition rate is estimated to be in the range 18–22 nm/hour from AFM measurements of the thickness of adsorbed carbon on the exposed sapphire regions of the substrate; note that the fraction of adsorbed carbon incorporated into epitaxial graphene on the adsorbed hBN flake is small, ~1%, so a growth time of ~4 hours is required to form a partial monolayer. The lifetime of the carbon source under these conditions is 2–6 hours so we are limited in our current work to monolayer growth. All of the samples discussed below were grown at the same substrate temperature which we estimate to be 1500 °C.We use a custom-designed dual-chamber GENxplor MBE system (base pressure ~10AFM images were acquired using an Asylum Research Cypher-S instrument operating in AC mode under ambient conditions and using Multi75AI-G cantilevers (Budget Sensors) supplied commercially by Windsor Scientific.Raman spectra were recorded on a Horiba–Jobin–Yvon LabRAM Raman microscope, with a laser wavelength of 532 nm operating at low power (~4 mW) and a 600 lines/mm grating. The detector was a Synapse CCD detector. The Raman shift was calibrated using an Si(100) reference sample. The Raman CLS map was obtained by extracting the 2D region of each spectra in the map. The model spectra were selected from the dataset to best represent the different regions observed in the map. The presence of a small carbon aggregate peak (blue spectrum) in the red shifted spectra (green and red) was removed by subtracting the blue spectrum after applying a multiplier to it to ensure complete subtraction of the unwanted feature. CLS fitting to each spectrum in the map was performed using the Horiba Labspec 6 software.How to cite this article: Summerfield, A. et al. Strain-Engineered Graphene Grown on Hexagonal Boron Nitride by Molecular Beam Epitaxy. Sci. Rep.6, 22440; doi: 10.1038/srep22440 (2016).


Self-heating induced failure of graphene devices synthesized from both chemical vapor deposition (CVD) and epitaxial means is compared using a combination of infrared thermography and Raman imaging. Despite a larger thermal resistance, CVD devices dissipate >3x the amount of power before failure than their epitaxial counterparts. The discrepancy arises due to morphological irregularities implicit to the graphene synthesis method that induce localized heating. Morphology, rather than thermal resistance, therefore dictates power handling limits in graphene devices. Epitaxial (Epi) graphene realized via the sublimation of silicon (Si) from silicon carbide (SiC) is limited only by the size of the supporting substrateBeyond the curiosity of an atomic dimension, it is the transport properties of graphene that differentiates it from traditional materials. Exhibiting a mobility that can exceed 200,000 cmThe same syntheses processes that provide scale, however, also induce morphological imperfections that limit device performance. Both epitaxial and CVD syntheses result in small regions of non-uniform layer number71012Self-heating of exfoliated graphene devices has been examined previously using infrared-thermography (IR)14151714141517e.g., SiO2) separating the graphene from the more thermally conductive substrate. While transfer of CVD graphene to SiC can capitalize upon the high thermal conductivity of the substrate, weak van der Waals bonding will result in a comparatively large thermal resistance at the interface 232425Solely from the perspective of thermal resistance then, epitaxial graphene provides an avenue to minimize self-heating and maximize power dissipation. Silicon carbide has a thermal conductivity ~3x that of silicon at room temperature21Self-heating is not determined exclusively from the thermal resistance, however, but also the area over which heat is generated. Factors localizing heat generation will exacerbate its effect. Here, we demonstrate that morphological imperfections localizing heat generation in a graphene device ultimately determine its power handling capability. Specifically, the breakdown power of epitaxial graphene on SiC devices is shown to be <3x that of comparable devices made up of CVD graphene atop a similar substrate. Correlations between the temperature distribution obtained with infrared–(IR) thermography and the morphology acquired using Raman imaging indicate that the difference arises from heat localization stemming from morphological features characteristic of the synthesis process. Altogether, the results demonstrate that the morphology of the graphene, rather than the system’s thermal resistance, dictates the amount of power that it can sustain.2 deposited via plasma enhanced chemical vapor deposition. This is termed— epitaxial/covered (Epi/Cov). The final architecture is composed of commercially synthesized CVD graphene  that is transferred to a SiC substrate and then covered with 50 nm of HfO2 realized via atomic layer deposition (ALD). This is termed—CVD/covered (CVD/Cov). Device geometries ranged in size from from 5 × 15 μm to 20 × 60 μm for each architecture and were contacted utilizing a Ti/Au stack (10/100 nm). Resistivity varied by ≤2x between the differing architectures and had comparable Raman responses largely absent of any defect signature (I(D)/I(G) ≤ 0.15, see Three graphene device architectures were fabricated at chip scale using standard photo-lithographic processes as shown schematically in 28For each architecture, six different devices of varying size were subject to increasing levels of Joule-heating until breakdown occurred. Breakdown was defined when channel resistance suddenly increased by several orders of magnitude. Only devices in which failure occurred in the channel—as opposed to the contacts—were included in the analysis. Practically, heating was induced by ramping current across the outer two leads to a target value held constant for 30s to facilitate thermography. Powers were measured by monitoring voltage across the inner contacts see . UtiliziBreakdown power differs significantly between the architectures see . Quantit2 carbon bonds limits the susceptibility of the graphene to electromigration2030Heating is of particular salience as the breakdown of graphene devices is thermal in origin203031et al.T > 1400 °C) than during the self-heatingExposed to the environment, graphene reacts with oxygen upon reaching temperatures of ~450 °C202/Si stack of an exfoliated device exhibits an out of plane thermal resistance of at least Ri = Li/Ki assuming thicknesses of 300 nm and 400 μm for the SiO2 and Si, respectively. Thermal conductivities of the two layers are presumed to be: KSi = 148 W/mKμm of SiC (KSiC = 450 W/mK) induces a resistance of RSiC = 0.9 m2K/MW —3x less than the exfoliated condition. Second, the exfoliated device possesses two thermally resistive interfaces—graphene to SiO2 and SiO2 to Si—to the epitaxial devices one—graphene to SiC. Third, the exfoliated devices have an area that is at least 8x less than the epitaxial devices. Under the assumption of uniform heating, these effects together will cause the exfoliated devices to heat up much faster and, by extension, fail at significantly lower powers. This is contrary to observation as, in reality, the epitaxial devices do not heat uniformly.Bare epitaxial devices failed at similar powers compared to previous reports of exfoliated devices see 20. This Epitaxial graphene emerges from the sublimation of Si from SiC resulting in concentration gradients of carbon that drive layer formation. The morphology of the underlying SiC affects the carbon concentration and thus the resulting graphene layerFor example, graphene multilayers form near atomic steps of the SiC leading to monolayer multilayer boundaries9Similarly, electrical resistance, and by extension heating, will increase locally in regions of lower mobility. Lower mobility has been correlated with regions of high variation in the 2D-mode peak positionLocalized heating and failure was also observed in epitaxial devices covered in an oxide implying that hot spot formation observed in 2. SiO2 degradation initiates at temperatures of 900–1000 °C3839402 as shown by the inset of Relative to the Epi/Bare device, the Epi/Cov architecture is capable of withstanding much larger powers see . The hig2, ALD layers of hafnia seeded with alumina begin to degrade near 900 °C43442 and HfO2 is ~900 °C. These oxides have negligible influence on the heat dissipation in either case since they are thermally insulative and extremely thin. Taken together, the difference in oxide species cannot be the cause for the 3x larger power handling capability of the CVD devices as compared to those epitaxially derived  Detector. A 20X objective having a lateral resolution of ~2 μm in size using standard photolithographic processes. Analogous CVD devices were fabricated by transferring ACS “Trivial Transfer” graphene onto 6H-SiC substrates using a procedure specified by the vendor. Conventional photolithographic techniques were employed to define and contact the devices2 was deposited using an established plasma enhanced chemical vapor deposition process.Quasi-free standing epitaxial graphene monolayer was synthesized using established methodologies292 was deposited using atomic layer deposition. To prevent graphene decomposition during the ALD process, a thin alumina layer is first grown onto the graphene surface. This protective alumina layer is formed by the controlled oxidization of a 10 Å, 0.2 Å/s electron beam evaporated aluminum thin film in pure oxygen at a partial pressure of 10 Torr. After a twenty minute exposure of the aluminum to this oxygen enriched environment, the high quality protective alumina layer is completely formed. This alumina layer not only serves to protect the graphene from potential reactants, it also appears to enhance the ALD hafnia nucleation process. Hafnia ALD was grown using a Picosun Sunale R150 hot-wall reactor operating at 250 °C using tetrakis(dimethylamido)hafnium(IV) (TDMAH) and deionized H2O precursors. At a source temperature of 75 °C, the TDMAH is introduced into the reaction space for a period of 1.5 s followed by a 15 s, N2 purge. To complete the formation of a single monolayer of hafnia, deionized water is then introduced for a period of 0.1 s followed by a 40 s, N2 purge. Both the TDMAH and H2O reaction cycles are repeated 550 times to grow a 50 nm hafnia gate dielectric.For the CVD/Cov devices, HfOHow to cite this article: Beechem, T. E. et al. Self-Heating and Failure in Scalable Graphene Devices. Sci. Rep.6, 26457; doi: 10.1038/srep26457 (2016).