Cardiovascular disease is prevalent in idiopathic pulmonary fibrosis (IPF), yet the extent of left-sided heart failure (HF) burden, whether this has changed with time and whether HF impacts mortality risk in these patients are unknown. The aims of this study were therefore to determine the temporal trends in incidence and prevalence of left-sided HF in patients with IPF in England and compare these to published estimates in the general population and those with comparable chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD), as well as determine the risk of all-cause and cause-specific mortality in patients with comorbid left-sided HF and IPF at population-level using electronic healthcare data.Clinical Practice Research Datalink (CPRD) Aurum primary-care data linked to mortality and secondary-care data was used to identify IPF patients in England. Left-sided HF prevalence and incidence rates were calculated for each calendar year between 2010 and 2019, stratified by age and sex. Risk of all-cause, cardiovascular and IPF-specific mortality was calculated using multivariate Cox regression.From 40,577patients with an IPF code in CPRD Aurum, 25, 341 IPF patients met inclusion criteria. Left-sided HF prevalence decreased from 33.4% (95% CI 32.2–34.6) in 2010 to 20.9% (20.0–21.7) in 2019. Left-sided HF incidence rate per 100 person-years (95% CI) remained stable between 2010 and 2017 but decreased from 4.3 (3.9–4.8) in 2017 to 3.4 (3.0–3.9) in 2019. Throughout follow-up, prevalence and incidence were higher in men and with increasing age. Comorbid HF was associated with poorer survival (adjusted HR (95%CI) 1.08 (1.03–1.14) for all-cause mortality; 1.32 (1.09–1.59) for cardiovascular mortality).Left-sided HF burden in IPF patients in England remains high, with incidence almost 4 times higher than in COPD, a comparable lung disease with similar cardiovascular risk factors. Comorbid left-sided HF is also a poor prognostic marker. More substantial reduction in left-sided HF prevalence than incidence suggests persistently high IPF mortality. Given rising IPF incidence in the UK, this calls for better management of comorbidities such as left-sided HF to help optimise IPF survival.The online version contains supplementary material available at 10.1186/s12890-022-01973-5. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease resulting in irreversible lung scarring. Due to diagnostic challenges, evolving diagnostic criteria as well as differences in study methodologies, estimates of IPF disease burden show substantial heterogeneity, ranging from a prevalence of 0.57–4.51 per 10,000 persons in Asia, 0.33–2.51 in Europe, and 2.40–2.98 in North America . For insHowever, while the high burden of CVDs such as IHD , pulmonaWhile there is evidence that IPF and left-sided HF co-exist, there are few population-level studies examining the epidemiology of left-sided HF in IPF patients, with generalizability of findings from existing studies made challenging by use of small cohorts from registries or single centres, frequent study of HF in only hospitalised patients, and lack of clear HF case definition . FurtherThe aim of this study was therefore to investigate temporal trends in incidence and prevalence of left-sided HF in IPF patients in England, compare this to published estimates in the general population and those with comparable chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD), as well as explore the risk of all-cause, cardiovascular and IPF-specific mortality in England using population-level electronic healthcare data. This is the first European study to explore temporal patterns of the burden of left-sided HF in IPF and one of few studies to date to investigate left-sided HF epidemiology in IPF using nationally representative population-level data.Data were obtained from the Clinical Practice Research Datalink (CPRD) Aurum, a nationally- representative database of de-identified primary care electronic healthcare records (EHR) covering approximately 19% of the UK population . Use of CPRD Aurum data for eligible patients registered in England was linked to secondary care data from Hospital Episode Statistics (HES), mortality data from Office of National Statistics (ONS) and socioeconomic data from the 2015 Index of Multiple Deprivation (IMD). Data linkage between sources was conducted by NHS Digital, a statutory trusted third party.https://github.com/NHLI-Respiratory-Epi/IPF_HF_codelists.Consistent with previous studies exploring IPF epidemiology by means of diagnostic codes in EHR , 36, we st January 2010–31st December 2019). For each patient, start of follow-up was defined as the latest of: 12 months post registration date with a general practice, start of study, patient’s 40th birthday or date of IPF-CS diagnosis. The end of follow-up was defined as the earliest of: transfer out of practice, end of study, last data collection date or patient’s date of death.We used a retrospective cohort study design with rolling entry and a 10-year study period  and based on previously published work were used to identify baseline covariates. Smoking, alcohol status and body mass index (BMI) were determined closest to start of follow-up. BMI data in the 3 years prior to start of follow-up was used, with BMI values calculated from height and weight data closest to start of follow-up, where available, in event of missing BMI data. Presence of baseline cardiovascular comorbidities and left-sided HF risk factors were determined at any point prior to start of follow-up, while cardiovascular medication use was defined as at least one prescription in the 12 months preceding start of follow-up. All codelists used, including those for ascertaining outcomes below, are accessible at: Codelists were also used to identify prevalent and incident left-sided HF. Codes denoting right HF were excluded.Cause of death was ascertained from ICD-10 codes using the derived cause of death field in linked ONS records. All-cause mortality was defined as death from any cause, with cardiovascular mortality defined as death due to myocardial infarction, ischaemic stroke or HF.Baseline characteristics are presented as absolute numbers and frequencies (%) for categorical data and medians with interquartile ranges [IQR] for non-normally distributed continuous variables. Proportions of missing data are described as frequencies (%) for each covariate.Left-sided HF prevalence and crude incidence rates were calculated annually for the 10-year study period, stratified by age  and sex. Incidence rates are reported per 100 person-years at risk, with associated 95% confidence intervals (CI).p < 0.05 level of statistical significance was used in all analyses. All analyses were conducted in Stata v16.0 .Multivariate Cox regression was used for mortality analyses. Covariate inclusion in the multivariate models was based on directed acyclic graphs (DAGs) created using clinical knowledge and existing literature to identify possible confounders  removing patients from the cohort diagnosed with IPF-CS post 1st September 2018 when ATS/ERS/JRS/ALAT IPF diagnostic guidelines changed (2) removing patients with non-specific IPF-CS diagnostic codes such as fibrosis of lung, pulmonary fibrosis, diffuse pulmonary fibrosis, Hamman-Rich syndrome, O/E-fibrosis of lung; (3) removing patients if they had evidence of another cause for pulmonary fibrosis or interstitial lung disease other than IPF, based on ICD-10 codes denoting an autoimmune condition, occupational lung disease, hypersensitivity pneumonitis or sarcoidosis in mortality data; and (4) removing patients diagnosed with IPF-CS when younger than 50 or 60 years old to exclude possible hereditary or familial IPF cases.For mortality analyses, ethnicity and IMD were also added as possible confounders in the multivariate models for all-cause and cardiovascular mortality.25,341 IPF-CS patients from 1379 general practices in England were included in the cohort  had HF diagnosed prior to IPF-CS, 3.7% were diagnosed concurrently with IPF-CS and 38.9% following IPF-CS.Those with comorbid IPF-CS and left-sided HF were more likely to be older, male, more socioeconomically deprived, have a higher BMI, be an ex-smoker, have a history of CVD or HF risk factors and be on cardiovascular medications at start of follow-up Table .Table 1BLeft-sided HF incidence rate per 100 person-years (95% CI) remained relatively stable between 2010–2017 but decreased modestly from 4.3 (3.9–4.8) in 2017 to 3.4 (3.0–3.9) in 2019  in 2010 to 20.9% (20.0–21.7) in 2019  than COPD patients [ref] and having comorbid HF is poor prognostic marker which increases risk of both all-cause and cardiovascular mortality, with a comparatively higher risk of the former than the latter.The modest reduction in HF incidence could reflect improved management of cardiovascular risk factors over time. Indeed, prescriptions for CVDs increased by 78% in England between 1991 and 2014 . By contWe were unable to ascertain from the data whether IPF patients with HF had HFrEF or HFpEF, although this would be useful to characterise. While HF prevalence has been noted to be increasing globally, many studies show a stable or decreasing HF incidence. An increasingly ageing population and improved HF survival due to treatment advances may explain increased prevalence while better treatment of acute coronary syndromes due to the advent of revascularisation therapies may explain reduced incidence of HF . FurtherAs discussed earlier, the treatment landscape of IPF has changed significantly in the last decade and it is unclear how these changing treatment patterns have influenced the burden of comorbidities such as left-sided HF in IPF. As antifibrotics are prescribed in tertiary care, we did not have access to antifibrotic use data in CPRD Aurum and therefore were unable to explore this potential association. Interestingly however, antifibrotics have been shown to have cardioprotective properties within the context of HFpEF, albeit this has not been explored specifically in the context of comorbid IPF and HF , 29. To Our HF incidence estimates are significantly lower than those reported by a US study, the only other population-based study which has explored the burden of left-sided HF in an IPF patient population. Using claims data between 2001 and 2008 for over 9000 patients, this study reported an incidence rate of 67.5 cases per 1000 person-years . Given tBy contrast, our prevalence estimates are higher than those from smaller cohort studies which range from 8 to 23% , 23–26. Consistent with other studies, male gender was found to be a significant risk factor for having a higher HF burden . AlthougBased on our estimates, left-sided HF prevalence is approximately 30-fold higher and incidence is almost 12-fold higher in IPF patients than in the general UK population . AssuminOur all-cause mortality estimates are in-keeping with two studies showing an increased mortality risk with comorbid IPF and HF, although our estimates are 29% lower than those in an Italian study , and thrWhile this study cannot explain why left-sided HF burden is so high in IPF relative to COPD patients, there are several possible theories. Shared risk factors such as smoking and ageing or shared pathological mechanisms such as telomere dysfunction and molecular and cellular fibrosis in both IPF and HF may contribute , 31. AltStrengths of this study include use of nationally representative population-level data linked to national mortality and secondary care data to explore left-sided HF epidemiology in IPF patients. This contrasts previous studies to date which have largely explored cohorts from single centres or registries. Although there is recognised heterogeneity in IPF coding terms in electronic healthcare records, left-sided HF incidence and prevalence estimates remained robust despite several sensitivity analyses optimising IPF case ascertainment. While there is potential risk of case misclassification due to dependency on codes entered in primary care, we draw confidence in the validity of ascertainment of both our exposure and outcome due to high positive predictive values (82–95%) of both HF and IPF diagnoses in primary care records , 34.Nevertheless, this study has several limitations. The cohort was predominantly Caucasian with patients residing in England, limiting generalisability of findings to other populations. Almost 80% of patients in the cohort also had non-specific codes for pulmonary fibrosis and although we used proxy measures in the sensitivity analyses to optimise IPF-CS case ascertainment such as exclusion of those with evidence of a potential non-idiopathic cause for pulmonary fibrosis based on mortality data, there is nonetheless a possibility that some cases were misclassified. A more comprehensive study of the validity of IPF codes in CPRD Aurum is currently in progress and would inform confidence in the results from this study. Furthermore, we did not have access to imaging data to determine IPF disease severity. This is important to ascertain as studies have shown IPF patients with a rapid disease course were more likely to be diagnosed with HF post IPF diagnosis . FurtherLastly, there was a significant proportion of missing data for alcohol intake, ethnicity and BMI. As missing data for these variables has been shown to not be missing at random in CPRD Aurum, we conducted a complete-case mortality analysis, but acknowledge this may have introduced some bias. For instance, patients with missing alcohol or BMI data are more likely to not have engaged with healthcare providers as often and by extension may have been less compliant with their medications or monitoring investigations for their IPF or HF. Therefore, it is possible that the patients excluded from the mortality analyses due to missing data may have generally been less healthy and may have had more severe disease severity of both their IPF and HF. The exclusion of these patients due to missing data may have therefore underestimated the risk of all-cause and cause-specific mortality in those patients with comorbid IPF and HF.This study shows temporal changes in both incidence and prevalence of left-sided HF in IPF patients in England, with modest reduction in incidence possibly reflecting improved screening and management of cardiovascular risk factors. However, despite decreasing incidence and prevalence, left-sided HF burden is considerably higher in IPF patients than in patients with other comparable chronic respiratory diseases and confers a higher mortality risk. Further studies are needed to explore HF phenotypes in IPF patients, whether there is a temporal relationship between the two diseases, what the aetiological mechanisms driving this association are, what drives the noted gender differences and whether HF treatment modifies the mortality risk.Additional file 1.Supplementary material.


Graphene-based materials have recently gained attention for regenerating various tissue defects including bone, nerve, cartilage, and muscle. Even though the potential of graphene-based biomaterials has been realized in tissue engineering, there are significantly many more studies reporting in vitro and in vivo data in bone tissue engineering. Graphene constructs have mainly been studied as two-dimensional (2D) substrates when biological organs are within a three-dimensional (3D) environment. Therefore, developing 3D graphene scaffolds is the next clinical standard, yet most have been fabricated as foams which limit control of consistent morphology and porosity. To overcome this issue, 3D-printing technology is revolutionizing tissue engineering, due to its speed, accuracy, reproducibility, and overall ability to personalize treatment whereby scaffolds are printed to the exact dimensions of a tissue defect. Even though various 3D-printing techniques are available, practical applications of 3D-printed graphene scaffolds are still limited. This can be attributed to variations associated with fabrication of graphene derivatives, leading to variations in cell response. This review summarizes selected works describing the different fabrication techniques for 3D scaffolds, the novelty of graphene materials, and the use of 3D-printed scaffolds of graphene-based nanoparticles for bone tissue engineering. There is a growing demand to engineer functional tissue using three-dimensional 3D) biological substitutes. Tissue engineering is a field composed of many scientific disciplines including biomedical engineering, cellular molecular biology, material science, and biochemistry. The concept of tissue engineering evolved in the 1990s whereby stem cells and materials could be implanted in vivo to restore injured tissues ,3,4. HowD biologiAlthough 3D printing is revolutionizing personalized treatment, the material needed to print the scaffold is a long-debated topic that depends on the desired tissue source to be repaired. These materials range anywhere from hydrogels, to nanoparticles, bio-metals, bio-ceramics, and bio-degradable polymers, each of which exhibit specific physicochemical properties. There are many material properties that influence tissue regeneration such as porosity, wettability, stiffness, strength, elasticity, biodegradability, and cytocompatibility. For example, a weight-bearing bone may require a stronger material that mimics the strength of the native tissue as the new bone regenerates, in comparison to a non-weight-bearing bone. Materials must withstand water absorption without rapid deterioration, yet gradually degrade overtime so that (1) new tissue can grow and function independently and (2) does not create a permanent implant. Additionally, many tissues require a 3D porous structure that allows blood vessel infiltration for constant nutrient transport as cells are building new tissue . The optFinally, tissue engineering materials must demonstrate properties of cytocompatibility, including cell adherence, cell viability, and stimulation of cell differentiation. Studies have shown that 3D scaffolds support cytocompatibility better than their 2D control counterpart ,26,27,28Carbon-based nanomaterials have gained attention for treating various tissue defects ,30,31. NCarbon nanomaterials include fullerenes, carbon nanotubes, nanodiamonds, carbon-based quantum dots, and graphene . Of thesPristine graphene, which is graphene in its original form, is hydrophobic (due to hydrocarbon contamination following air exposure) thereby lacks dispersion in water which raises aggregation/toxicity concerns when delivered in vivo . This lireducing the number of oxygen atoms found in GO. Reports estimate that rGO restores 80% sp2 structure with the remaining sp3 bonds derived from residual oxygen (C:O = 13:1) . S. S55]. SInterestingly, Nalesso et al. reported in vivo bone regeneration in critical sized defects using 3D printed scaffold of PCL and graphene nanoplatelets. In fact, the team fabricated electroactive scaffolds which enhanced bone regeneration in a rat calvarial bone defect model. Electroactivity of the scaffolds was modulated by varying the amount of graphene used . Two recAlternatively, other laboratories have coated graphene onto 3D scaffolds to enhance mechanical strength and cytocompatibility ,83. For It has thus, been established without a doubt that 3D construction of graphene scaffolds is the next step for clinical translation in tissue engineering. This research is important as the last decade of traditional 2D cell culture systems have shown that graphene substrates support stem cell differentiation into various lineages. These cell lineages are influenced by the concentration of graphene, its functionalization, shape, and the stem cell source ,86. But Although graphene materials have rapidly emerged as bone substitutes, few studies have examined the mechanisms behind its ability to induce osteogenesis. Some theories suggest the carbon arrangement imitates an organic bone ECM microenvironment, attracting cells to attach, self-renew, and differentiate . An ECM Despite this excitement, a major question is determining the best concentration and form of graphene that specifically sustains bone differentiation without collateral damage. BM-MSCs cultured on GO (0.1 µg/mL) had increased proliferation rates; however, at high GO concentrations (10 µg/mL), the BM-MSCs shrank and subsequently had reduced cell proliferation after just 3 days of culturing . SimilarDespite this ongoing challenge, graphene materials have versatile ways in influencing bone regeneration. For example, graphene can indirectly support bone regeneration as a delivery vehicle that controls the release of potent BMP2 growth factors ,106,107.Even though the potential of graphene and its derivatives in biomedicine has been realized, and, as described in the above section, 3D-printed scaffolds are important for the success of a bone tissue engineering strategy, practical applications of 3D-printed graphene scaffolds are still limited. Despite the availability of various 3D-printing techniques including fused deposition modeling, direct ink writing, selective laser sintering, and stereolithography, the use of 3D-printed scaffolds in human or veterinary medicine is limited. This can be attributed to variations associated with graphene manufacturing processes, leading to variations in cell response. For instance, the flaky texture of pristine graphene resembles sawdust particles, and thus is not a candidate for direct printing. In other words, the flaky texture draws challenges in creating pure graphene scaffolds via 3D-printing. This limitation is addressed by incorporating graphene flakes within a polymer  ink that sustains a 3D shape upon printing ,115,116.Despite the excitement of graphene materials and their use as a 3D scaffold for tissue engineering, their therapeutic use is still a novel idea and has yet to undergo a human clinical trial. As with any new substance, the primary question to address will always be safety. Since graphene nanoparticles exist in a variety of sizes (1 to 100 nm in length and 1–10 nm in thickness), and derivatives (oxidized or reduced with varying oxygen content), each form exhibits unique physicochemical properties, which can pose occupational and environmental risks to humans and animals. Information ,118 regaThere are a growing number of in vivo reports regarding the toxicity of graphene materials ,125,126.Wang et al., 2011, evaluated GO toxicity in mice after 30 days of exposure to one of three concentrations: 0.1 mg, 0.25 mg, or 0.4 mg . ResultsA similar study from a separate laboratory also examined GO toxicity in mice following a low dose (1 mg/kg body weight) and a high dose (10 mg/kg body weight) via IV injection . After 1With growing pulmonary toxicity concerns, Singh et al., 2012 compared the lungs of mice injected with either GO or graphene that was functionalized with amine groups (G-NH2) . After 1Schinwald et al., 2012 evaluated the risk of graphene nanoplatelets (GP) (average thickness of ~10 nm) following either inhalation or intrapleural injection in mice . For inhAmrollahi-Sharifabadi et al., 2018 studied graphene oxide nanoplatelets (GONs) and how various doses measured using hematological and histological parameters after 21 days in vivo. They concluded that four cumulative doses of 50 (200 mg/kg) and 150 (600 mg/kg) did not show any toxicity effects in the serum levels, liver, kidney, spleen, lung, intestine, brain, or heart. However, 500 (2 g/kg) showed a significant change in all levels except the heart .Most recently, Tabish et al., 2018 studied the toxicity of graphene nanopores (GNP) after a single IP injection or multiple injections  over 27 days at doses of 5 mg/kg or 15 mg/kg in a rat model . All dosConventional strategies of repairing tissue defects have relied on exogenous stem cells and 2D substrates. However, stem cell-based therapies have many limitations with future strategies turning to 3D structures that both support and attract cell differentiation within the injury site. Graphene, a carbon-based biomaterial, is under thorough research for repairing various tissues such as bone, cartilage, nerve, and heart. However, in vitro work of graphene has mainly been studied as a 2D monolayer or a 3D foam, whereby scaffold morphology is poorly controlled. With the revolution of 3D-printing technology, questions have asked whether graphene scaffolds can be 3D printed. Currently, there is a paucity of studies that have attempted 3D-printed graphene scaffolds for tissue engineering. These studies have mainly surfaced in the last few years, but it is expected that more developments will evolve in the future. Finally, 2D-graphene substrates have predominantly been studied in supporting new bone differentiation. Therefore, 3D-printed graphene scaffolds are the next step for clinical application in bone tissue engineering. However, understanding the optimal concentration of all graphene derivatives that balances both bone differentiation and minimizes toxicity is necessary prior to transplantation. Overall, there is great excitement over 3D-printed graphene scaffolds, but much work is necessary before standardization within tissue engineering.


The role of humidity sensors in different industries and field applications, such as agriculture, food monitoring, biomedical equipment, heating, and ventilation, is well known. However, most commercially available humidity sensors are based on polymers or electronic materials that are not degradable and thus contribute to electronic waste. Here, we report a low-cost, flexible, easy-to-fabricate, and eco-friendly parallel-plate capacitive humidity sensor for field applications. The sensor is fabricated from copper tape and tissue paper, where copper tape is used to create the plates of the capacitor, and tissue paper is used as a dielectric sensing layer. Along with the low cost, the high sensitivity, better response and recovery times, stability, and repeatability make this sensor unique. The sensor was tested for relative humidity (RH), ranging from 40% to 99%, and the capacitance varied linearly with RH from 240 pF to 720 pF, as measured by an Arduino. The response time of the sensor is ~1.5 s, and the recovery time is ~2.2 s. The experiment was performed 4–5 times on the same sensor, and repeatable results were achieved with an accuracy of ±0.1%. Furthermore, the sensor exhibits a stable response when tested at different temperatures. Due to the above advantages, the presented sensor can find ready applications in different areas. With the advancement of automation and technology, there is an exponential increase in the demand for electronic devices and sensors. This leads to an increase in the production of electronic devices, such as sensors, smartphones, computers, and IoT devices. However, the increase in the production of electronic devices is also increasing electronic waste (e-waste). E-waste has severe environmental implications as it is not degradable and can end up in landfills or oceans. It is estimated that the e-waste produced in 2021 alone is 57.5 million metric tons, of which only 17% has been recycled ,4,5. TheAmong the sensors, humidity- or moisture-based sensors have been extensively studied due to their importance in different industries and field applications, such as agriculture, food monitoring, biomedical equipment, heating, and ventilation ,22,23,24On the other hand, resistive humidity sensors make use of a change in resistance to establish the level of humidity. Capacitive humidity sensors are often preferred over resistive sensors, owing to several advantages. The basic structure in capacitive humidity sensors is of two types: interdigitated (IDE) and parallel-plate (PP) . In PP cIn this work, we have presented a PP humidity sensor based on eco-friendly materials, such as copper tape and tissue paper. The plates of the capacitor are made of copper tape, whereas tissue is used as the hygroscopic dielectric layer to absorb the moisture. The lower plate is a plane of copper tape, while the upper plate has pores to allow moisture to be absorbed by the tissue. The performance of tissue as a sensing layer is superior to various polymer-based sensing layers, such as polyethylene terephthalate (PET), polyimide (PI), or Kapton, in terms of sensitivity, response time, and stability. The sensor was tested for the range of 40% to 99% RH, and the capacitance varied linearly with RH from 240 pF to 820 pF. The sensor has a fast response and recovery times of 1.5 s and 2.2 s, respectively. The effect of temperature on the working of the sensor was also investigated, and the sensor exhibited reasonable sensitivity at different temperatures as well. The experiment was repeated 4–5 times on the same sensor, and the repeatability achieved was within ±0.1%.The physical dimensions and a picture of the sensor are shown in A capacitive sensor works on the principle of change in capacitance as the humidity varies ,35,36,37The sensor was tested in a homemade humidity chamber equipped with a heater, humidifier, and dehumidifier so as to control the humidity as well as the temperature as shown in To test the sensor, the RH in the chamber was initially set to 45%. At this value of RH, the sensor had a capacitance of 240 pF, as measured by the Arduino. The RH was gradually increased to 100% by turning on the humidifier. The increase in RH increased the capacitance of the sensor, which reached 850 pF at 100% RH, as shown in The sensor has a capacitance of 240 pF at 45% RH. When RH is increased with the help of the humidifier, the capacitance increases along with it. Different values, such as 60%, 70%, 80%, 90%, and 100%, of RH were maintained inside the chamber, and the capacitance values varied in accordance instantly. The measured values of the sensor’s capacitance at different levels of RH are shown in g layers  and manig layers . The seng layers :(1)S=ΔCΔThe stability and repeatability of a sensor are key parameters for evaluating sensor performance. To test these, we performed repeated cycling of sensors at different temperatures for 7 consecutive days, as shown in The comparison of the sensing parameters of our sensor, such as sensitivity, response time, and recovery time, with previously reported work is presented in In this paper, an easy-to-fabricate and cost-efficient copper-tape-based, parallel-plate capacitive humidity sensor has been studied. The sensor is fabricated by using copper tape to make the plates of the capacitor, whereas tissue paper is used as a dielectric sensing layer. The sensor was tested in a homemade humidity chamber with a built-in DHT22 sensor, humidifier, dehumidifier, Arduino Mega 2560, and electric heater. Along with high performance in terms of response time and recovery time, sensitivity, repeatability, and stability, the use of such green sensors would certainly help reduce the e-waste that adversely affects our planet. Due to these advantages, such sensors can be used for various industrial and field applications.


This result can be considered as the first realization of local tunable bilayer graphene diamondization.In the presented paper, we studied bilayer CVD graphene transferred to a langasite substrate and irradiated with a focused electron beam through a layer of polymethyl methacrylate (PMMA). Changes in the Raman spectra and an increase in the electrical resistance of bigraphene after irradiation indicate a local phase transition associated with graphene diamondization. The results are explained in the framework of the theory of a chemically induced phase transition of bilayer graphene to diamane, which can be associated with the release of hydrogen and oxygen atoms from PMMA and langasite due to the “knock-on” effect, respectively, upon irradiation of the structure with an electron beam. Theoretical calculations of the modified structure of bigraphene on langasite and the experimental evaluation of sp Graphene, due to its outstanding properties, has the widest range of applications  was loaded into a CVD reactor and evacuated to base vacuum pressure (<10−4 Torr). The temperature in the chamber with a mixture of Ar (2000 cm3/min) and H2 (30 cm3/min) was raised to 1060 °C at an operating pressure of 470 Torr. The copper foil was annealed at 1060 °C with a mixture of Ar (2000 cm3/min) and H2 (30 cm3/min) at an operating pressure of 470 Torr for two hours. Graphene layers began to grow on copper foil at 1020 °C when a mixture of methane and hydrogen (CH4 = 40 cm3/min and H2 = 100 cm3/min) and 2000 cm3/min Ar as the carrier gas was introduced into the reaction chamber at 600 mTorr. After 30 min, the reaction chamber was cooled to room temperature at an average rate of 14 °C/min at the same flow rates of Ar/H2 gas, without methane.Graphene monolayers were obtained by chemical vapor deposition (CVD) on a copper catalyst foil. The CVD reactor we used was a horizontal quartz tube 2400 mm long and 152 mm in diameter. This quartz tube was placed in a six-zone furnace 1500 mm long. A 25 µm thick copper foil  (langasite) substrate using a 2 µm thick electron-resist polymethyl methacrylate , which was spin-coated onto the synthesized graphene at 3000 rpm for 100 s. PMMA was dried in an oven at 120 °C for 10 min. Since graphene layers grew on both sides of the copper foil during chemical vapor deposition, the removal of graphene layers from the reverse side of the foil was carried out in oxygen plasma with a power of 60 W for 10 min. Then the copper foil was removed in a copper etchant  for 40–60 min. To wash graphene after copper etching, PMMA/graphene was placed successively in two water baths for 20 min at a time. After washing with distilled water, the PMMA/graphene layer was transferred onto an LGS substrate. The PMMA was then removed with acetone in an ultrasonic bath for 20 min, leaving single layer graphene (SLG) on the LGS substrate. Then, the SLG on LGS was washed with a 30% HCl solution at 60 °C for 30 min to remove residual Fe3+ ions. As a result, a pure high-quality graphene layer with a low defect density was prepared on the LGS substrate. The next layer of graphene was transferred using the same procedure. Before transferring the upper layer, the surface of the lower layer was thoroughly cleaned with solvents and an ultrasonic bath to ensure a tight fit of the graphene monolayers to each other.Two grown graphene monolayers were transferred to a polished surface of a lanthanum gallium silicate  with a 100× objective , a 532 nm (488 nm) laser with a power of 1 mW , and a GX polarized filter-AN360 (Olympus). Each spectrum was obtained by 10 measurements within 10 s of the accumulation time. For each sample, 3 to 6 analyzes were performed at different locations. Then, a layer of PMMA-950 resist, 300 nm thick, was deposited on the LGS substrate with bigraphene by centrifugation. These samples were irradiated using an EVO-50 scanning electron microscope equipped with Nanomaker electron beam control. The Raman spectra of nanostructures obtained by irradiation with a focused electron beam were measured using a Bruker Senterra micro-Raman system. The excitation wavelength was 532 nm; laser power at the sample point was 10 mW; the capture was 2 × 20 s at each point on the map. Transport measurements of nanostructures were carried out using a microprobe station EPS150TRIAX and a Keithley 2636B System SourceMeterc axis was set to be greater than 15 Å. The langasite model has a thickness of ~1 nm (two unit cells) with a frozen bottom layer.All calculations were performed within density functional theory (DFT) ,25 in th2 was fabricated. Unmasked graphene was removed from the substrate in oxygen plasma. Thus, a double layer of graphene with an area of 1 mm2 remained on the LGS substrate, to which four contacts, 100 nm thick, consisting of an alloy of gold and chromium in a ratio of 20:1, were attached using electron beam lithography (see x) resist which was previously demonstrated as a source of hydrogen released during the development of the resist and forming sp3 bonds with graphene [x, causes the problem of cleaning the treated layer from residual resist contamination. The use of PMMA solves the problem of graphene contamination as PMMA dissolves in acetone, almost without residue.A schematic representation of the irradiation experiment is shown in aphy see b. At thegraphene ,32. The 2 were irradiated at three accelerating electron beam voltages of 5 kV, 15 kV, and 25 kV at a beam current I = 1 nA  to 4 mC/cm2. After irradiation, the irradiated areas were developed and examined. The analysis showed that, with an increase in the density of the implanted charge (irradiation dose), structural changes occurred in the double graphene layer. The use of doses above 1 mC/cm2 resulted in PMMA-950 crosslinking, so they were not used in subsequent experiments. With a decrease in the accelerating voltage, the threshold dose sufficient for resist crosslinking decreases due to an increase in the effective absorbed-beam energy. Therefore, the accelerating voltage of U = 25 kV was chosen as the optimal value.Bigraphene squares with an area of 0.25 mmI = 1 nA b. The ir2. Based on the data obtained, we chose the optimal conditions for a local chemically induced phase transition in bilayer graphene to form the bigraphene/diamane/bigraphene nanostructure and measured its transport characteristics. The scheme of the experimental sample and the image of the investigated LGS/bigraphene/Cr/Al/PMMA structure irradiated with an electron beam are shown in For U = 25 kV, the maximum possible radiation dose that does not lead to crosslinking of the resist is 1 mC/cmAs shown in Measurements of the I–V characteristics of the nanostructure between contacts to the graphene bilayer in the longitudinal direction to the irradiation line a show a Transport measurements show that the resistance of the graphene bilayer after irradiation with an electron beam increases significantly. The linear dependence of current on voltage in the bias voltage range from −1 to 1 V changes to a nonlinear one. This indicates the formation of a semiconductor phase with higher electrical resistance.3-hybridized carbon density. The width (FWHM) of the 2D band also shows a significant increase from 43 cm−1 for the initial bigraphene to ~100 cm−1 for the irradiated points. The Raman mode of carbon at ~1345 cm−1 is associated with defects responsible for the formation of sp3-hybridized regions, which is commonly observed in graphene oxide (GO). Previously, we have shown that electron beam irradiation of GO leads to its effective reduction with a decrease in the sp3-hybridized carbon density and a relative decrease in the intensity of the D peak without its shift [−1 and an increase in intensity /I(G) ratio in graphene; the SC parameter is the value of the I(D)/I(G) ratio in the highly disordered limit; Sr and Ar are the radii of two circular areas measured from the defect site. The first length, Sr, is the radius of the structurally disordered area around the defect, so it is expected to change from defect to defect. For distances larger than Sr but shorter than Ar, the lattice structure is preserved. However, the proximity to a defect causes the mixing of Bloch states near the K and K′ valleys of the graphene Brillouin zone and, therefore, breaking of selection rules and leading to an enhancement of the D band. If we accept that defects of the “vacancy” type can be neglected, then the concentration of sp3 carbon can be estimated from the ratio of the intensities I(D)/I(G) and I(D′)/I(G), which gives the maps shown in The 3 carbon in the irradiated region is about 1012 cm–2 (3 hybridization. Such behavior of graphene is typical upon the attachment of reference atoms to it. In the case of a single layer of graphene in this way, it is possible to obtain the “ultimate diamond slab” [2 to sp3, leading to a change in the chemistry of neighboring C atoms, that in turn tend to connect with other atoms. In the case of a multilayered film, such atoms are carbon atoms from the neighboring layer, which leads to the bonding of the layers to each other and the final formation of a diamond film [Our estimates show that the fraction of sp012 cm–2 c,d. Whennd slab”  (graphanond film .In the present case, graphene is exposed to oxygen atoms from one side and hydrogen atoms on the other side forming a Janus diamane structure. We designed the corresponding model of diamane film arranged on the LGS substrate functionalized by the hydrogen atoms from the outer side. During the relaxation surface, oxygen atoms of langasite shifted and connected with the carbon atoms on the interface-stabilizing diamane geometry. The final structure of hexagonal diamane film with the  surface a showed The observed high resistivity of the diamondized graphene regions is explained by the density of electronic states b where f3 carbon density observed in modified bigraphene indicates the formation of a diamane nanocluster in irradiated area. It is probably caused by the non-optimal stacking of carbon atoms in two functionalized graphene layers, which is determined by the angle of rotation between the two layers [It should be noted that the low spo layers . Other p3 bonds of carbon with hydrogen and oxygen. When a certain local area of the sample is irradiated with a focused electron beam, hydrogen is released from the destroyed polymer from one side and oxygen is taken from the LGS substrate on the other side, forming stable bonds with graphene. It results in the formation of a diamane nanocluster structure in the bigraphene irradiated area. The designed model of diamane film arranged on the LGS substrate and functionalized by the H and O atoms supports the experimental observations.The presented study is devoted to the investigation of the effect of chemically induced phase transition in bilayer graphene transferred onto a langasite substrate and irradiated with a focused electron beam through a layer of polymethyl methacrylate. Transport measurements show that the resistance of the graphene bilayer after irradiation with an electron beam increases significantly, and the linear dependence of current on voltage in the bias voltage ranges from −1 to 1 V changes to a nonlinear one. This indicates the appearance of a barrier for the carriers in the irradiated region. This result is explained in the framework of the theory of a chemically induced phase transition associated with the formation of sp


This may be taken as a predictor of the writing quality in argumentative compositions by EFL. Pedagogically, the study emphasizes the significance of teaching DMs, where EFL learners should be taught how to use them appropriately to avoid any transference of their L1. Further research on DMs in argumentative writings in different levels of proficiency is recommended.The aim of the present study is to investigate the use of discourse markers (DMs) in the argumentative compositions written by EFL learners at two academic stages (sophomores and seniors) majoring in English at the Hashemite University, Jordan. The significance of this study springs from its focus on the use of DMs in Jordanian EFL learners’ argumentative writings. Employing an integrated research method of qualitative and quantitative analysis, the findings revealed that both groups of participants used the same types of DMs with varying degree of frequency, namely, elaborative, contrastive, reason, inferential, conclusive, and exemplifier DMs, respectively. The sophomores were observed to employ a relatively higher number of DMs compared to the seniors, which may be ascribed to some redundant instances of DMs. The elaborative, contrastive, and reason types were the most widely used, while inferentials, conclusives and exemplifiers appeared infrequently in both groups. The analysis of individual DMs displayed that the DMs ‘and’, ‘because’, and ‘but’ were the predominant across the seniors and sophomores’ argumentative texts. This overuse of these DMs may be due to the influence of L1 of the participants and the popularity of these DMs among students and teachers of English. Additionally, the participants showed a low proficiency in using DMs since they overused largely a restricted variety of DMs at the expense of others that would be expected in the argumentative writing; some DMs were noticed either to be underused or absent. The results of Pearson’s  The reason beyond the choice of this type of writing is that it has been characterized as the hardest type in both L1 and L2, in comparison with other types of writings such as narrative and expository  at the Hashemite University, Jordan. All of them were EFLs (their native language is Arabic), aging between 18 and 22. During the spring semester 2019–20, a total of 120 students were selected randomly from eight classes.basic grammar course and paragraph writing course, and the second group consists of 60 seniors who all passed advanced grammar course and essay writing course. These courses were based on to select the participants of the study, where the former two courses are required for sophomores and the latter two courses are required for seniors. Grammar courses help students gain systemic knowledge of English grammar , meanwhile writing courses improve students’ writing ability skills (successful paragraph and essay development)The students were divided into two groups: the first group consists of 60 sophomores who all passed ‘Online education is rapidly increasing in popularity. Some people think that online teaching is as effective as in-person instruction, while others think online teaching is inferior. Discuss both these views and give your own opinion.’In order to ensure the homogeneity of the participants in the study and to cover all proficiency levels to get realistic results, the participants were of different gender  and GPA (ranging from good to excellent). The data of the present study is argumentative texts with a minimum word-count of 250 words on the online-learning. The following task was given to the participants:This topic was chosen in particular because the Hashemite University students have experienced online learning over the past few years. The onset of Covid-19 pandemic has led to such a significant development in online learning. Therefore, we believed that the students are able to argue about this topic easily because they are aware of the advantages and disadvantages of the issue , the students were given 40 min to write the task. All of the 120 paragraphs were examined. The process of identification of DMs in the compiled data draws mainly on Fraser’s , 2006 lir = 1 means a positive linear correlation, r = −1 means a negative linear correlation, and r = 0 means no linear correlation. Finally, to compare the results of both groups of students, the means and standard deviations were measured and an independent-samples t-test was carried out to test the significance of difference between the two groups.To obtain statistical values concerning writing quality, a Pearson’s r correlation test was applied to find out whether the frequency of the use of DMs and writing quality are correlated or not. Pearson’s r correlation is used to measure the strength of a linear correlation between two variables, where the value The quantitative analysis of data by means of the Wordsmith concordance software showed that the entire data set had a sum of 802 occurrences of 25 different DMs in the argumentative compositions. Tables and the student himself. And online learning gives us more information and we can search about anything in it, and we can watch the online course more than one time to understand what it is talking about”.“Online learning depends on internet and in the same minute, you can share your information and make a conversation about it, and the teacher gives you homework to improve your skill.”“Classroom room learning have advantage like you can ask your teacher about anything you can’t understand. It can be noticed that both groups used the same types of DMs with varying frequencies. The number of DMs used by both groups revealed that there was no statistical difference, where the total frequency of DMs in the seniors’ argumentative texts was 415 occurrences and 387 in their sophomores’ counterparts. The reason why seniors employed a less number of DMs than did the sophomores may be attributed to the notion that the seniors tended to avoid overusing or redundant instances of DMs observed in the sophomores ‘compositions. This finding is in line with Altenberg & Tapper , who fouAs shown in Table The statistical findings revealed, as displayed in Table This high percentage of the occurrence of elaborative, contrastive, and reason DMs can be attributed to the argumentative mode of the respective texts written by the sophomores and seniors, where they require to employ such DMs for adding new arguments, contrasting ideas, and justifying standpoints. While it was found that the most frequently used types were elaborative DMs, followed by contrastive DMs in the present study, Polish undergraduate learners of English were reported to make more use of the contrastive type than the elaborative one in their argumentative essays Sanczyk, .A further analysis of the DMs in the data under examination revealed that elaborative type ranked by far the highest in terms of frequency. It made up 49.9 % of the entire occurrence of DMs in the sophomores’ text and 40% in the seniors’ text. Among this type, the most commonly used DM was, as shown in Table wa:w ‘and’.The overuse of ‘and’ in both groups is not surprising for two reasons. On one hand, preceding research findings report that EFL learners (regardless of their L1) are likely to employ more ‘ands’ than native speakers of English Taweel, . On the This overreliance on ‘and’ may signal a low proficiency in the use of DMs in the students’ argumentative writing Uzun, . StrikinMore elaborately, the overuse of ‘and’ can be due, to a greater extent, to the negative transfer from Arabic as the mother tongue of the leaners, where the DM ‘wa’ ‘and’, in Arabic, is poly-functional that it serves various functions such as, in addition to elaborative, contrastive, causal, and temporal Hamed, .However, it seems that the seniors employed ‘and’ less frequently than the sophomores who largely overused it. This indicates that there was some kind of development/ improvement in the proficiency level of the seniors as they incorporated other elaborative DMs more frequently than those by the sophomores, reducing dependence on ‘and’ in favor of other DMs. Moreover, it is worth mentioning that EFL learners used largely elaborative DMs in argumentative compositions in an attempt to explain, support, and develop their point of view in details, thus, make their thesis statement more well-expressed and persuasive.Overall measures of DMs in both groups have shown that there is a relative decrease in the occurrences of the elaborative DM ‘and’ by seniors and increase of other elaborative DMs such as ‘also’, ‘furthermore’, ‘in addition’, compared to the sophomores, who used ‘and’ more repeatedly in their texts. That is, there is a common tendency among seniors to employ more frequently diverse elaborative DMs than sophomores.As for the contrastive DMs that came the second in frequency in both groups, they were frequently used in comparison with other DMs such as, inferential and conclusive categories (the sophomores 18.3% and the seniors 26.9%). By contrast, Jalilfar  reportedRanking the third largest category in both groups, the category of reason DMs was relatively moderately used by both groups . Dissimilar to these findings, it was reported that reason DMs were the most widely used by Turkish learners of English in their argumentative essays Altunay, . Among tLess frequently used types in the data were conclusive and exemplifier DMs. The former was used 5.1% by the sophomores and 8% by the seniors whereas, the latter was used 6.5% by the sophomores and 8.8% by the seniors. Only three conclusive DMs  were employed by both the sophomores and seniors. Comparing the both groups, the conclusive type had a higher frequency in the seniors’ argumentative texts than the sophomores’ texts. The DM ‘in conclusion’ was the predominate one among this type, while the others were mostly underutilized, where its total frequency in the whole data in both groups was 3.4% by sophomores and 5.7 % by the seniors. Concerning exemplifiers, like the conclusive types, only three DMs  appeared in the data. The findings showed that the most commonly used one in this class was ‘for example’ in the sophomores’ texts and ‘such as’ in their counterparts. It seems that these two categories appeared more in the seniors’ argumentative compositions. This evidently indicates that there is a development in the seniors’ proficiency level as compared to their counterparts regarding using exemplifiers to give examples as evidence in order to support their argument and conclusives to signal that they have reached the end of the composition and will summarize what has been argued for or against.As given in Table A closer analysis of the individual DMs used in the argumentative texts written by sophomores and seniors revealed that the most commonly used DMs across both groups of learners were ‘and’ 36.1%) (23.2%), ‘because’ (14.2%) (10.6%), and ‘but’ (9.6%) (9%), respectively. There were no differences in the frequency order of these three DMs between the two groups of leaners. However, they displayed some differences in the number of their occurrence in each group. As shown in Table 6.1% 23.. Such fiOn the ground of these results, it is justifiable to infer that since both groups of learners in this study utilized frequently a very limited number of DMs in their argumentative texts, they had a poor proficiency level of using DMs, compared to higher proficient L1/ L2 writers Zhang, . The impt-test was undertaken in order find whether there is any statistically significant difference between the sophomores and the seniors’ use of DMs in their argumentative written texts. As displayed in Table M = 69.17, SD = 72.07) and seniors  in their use of DMs in argumentative papers; t(10) = 0.126, p = 0.901.To address the second question of the present study, an independent-samples More elaborately, the total occurrences of the DMs found across argumentative compositions written by the two groups in this study was 802, as clearly illustrated in Table r correlation test was carried out to assess this relationship. As illustrated in Table r(58) = .32, p = 0.012. Likewise, the frequency of DMs and the evaluation of the seniors’ writings were found to be weakly positively correlated, r(58) = 0.42, p < 0.001. Based on the results obtained from the present correlation test, it can be stated that a positive correlation but significant (the sophomores 0.012656 and the seniors .000764) was found between the total use of DMs and the quality writing of the argumentative texts written by the participants of the present study. It can be suggested that the highly-rated argumentative compositions tend to employ more DMs than did their poorly-rated counterparts.With regard to the last question of the study concerning the relationship between the frequency of DMs and the quality of writing, a Pearson’s Although the results of the present study revealed that there was a positive correlation between the two values at issue, the relationship between the frequency of DMs and the evaluation was weak . However, we can infer that the frequency of DMs can be, to some extent, a potential predictor/ indicator of writing quality, that is, the higher the number of DMs, the better the quality of writing. Such findings are in line with the studies that support the existence of a positive correlation between the deployment of DMs and the quality of writing Jin, . This imHowever, it should be borne in mind that correlational tests do not always suggest causation- that when two variables in tandem do not necessarily indicate that one variable is affecting the other.  or were only used by one group . Remarkably, it was found that an array of manifold DMs was never used neither by the sophomores nor by the seniors .The findings indicated that there was a weak positive but significant correlation between the use of DMs and the quality of writing in both argumentative texts written by the sophomores and seniors.Based on the present findings on the use of DMs in the sophomore and seniors’ argumentative writings, some pedagogical implications can be highlighted. As we have seen, the use of DMs in argumentative writings presents a challenge to EFL learners across different levels of proficiency. Moreover, the analysis reveals that EFL learners demonstrate little variety in the use of DMs.The inappropriate use of DMs should be attended to by both instructors and learners. More focus should be placed on DMs and students should be exposed to more varied DMs. In other words, instructors of English should familiarize their students with a wide variety of DMs and encourage learners to vary in their choice of DMs in their writings rather than relying on restricted range of DMs. To increase the quality of EFL argumentative writing, learners should be given more exercises on the functions of DMs and their role in creating and maintaining the cohesion and coherence of text, especially, in academic writing (For details, see Guba et al.,


The aim of this survey was to establish how higher psychiatry trainees are using special interest sessions. Special interest sessions provide trainees with the opportunity to gain additional experience and are defined as ‘a clinical or clinically related area of service which cannot be provided within the training post but which is of direct relevance to the prospective career pathway of the trainee.’ The Curriculum for Specialist Training in Psychiatry states that two sessions every week must be devoted during each year of Specialty training for such personal development, which may be taken in research or to pursue special clinical interests.st March 2021 and 1st April 2021. The survey included multiple choice and open questions relating to the accessibility, use and content of special interest sessions. Participants were asked to comment on their experiences. Quantitative data were analysed using Excel and qualitative data were collated and reviewed.All higher psychiatry trainees working within Health Education England (HEE) Wessex Deanery were invited to complete a survey using Google Forms between 120 of the total 42 higher psychiatry trainees responded with the highest response rates from trainees in Old Age Psychiatry and dual training posts. 25% were using all their entitled special interest sessions. The remaining trainees were not able to use them consistently due to clinical service demands and 10% were not using any due to being unaware of opportunities available.The majority of trainees were using special interest sessions for research, followed by postgraduate qualifications and psychotherapy. Other special interests included medical education, management experience and psychiatric liaison. 70% found their special interest sessions straightforward to arrange and supervisors were highlighted as a useful support.Most trainees did not have a good awareness of special interest opportunities available within their specialty. 90% would like to be better informed of opportunities for special interest sessions.The survey indicated that the majority of higher psychiatry trainees are having difficulty accessing special interest sessions due to clinical service demands and a lack of awareness of opportunities available. In order to meet Curriculum requirements, it is important that trainees are supported by supervisors and trusts to access special interest sessions. Specialty training job descriptions should allow for special interest time with appropriate cover arrangements. To improve awareness of special interest sessions, I have developed an information booklet listing opportunities available for higher psychiatry trainees in HEE Wessex Deanery.


Aspergillus spp (including azole-resistant strains), rare, resistant moulds  and dimorphic moulds.Olorofim is a novel antifungal agent active against Serial images of Lomentospora prolificans infection following breast enhancement surgery: progression of healing pre- and post-olorofim therapy.Post-surgical bone/ soft tissue Lomentospora prolificans infection of the chest wall in a healthy woman was uncontrolled with available agents (D -9 visible mould in wound base). At D42/84 overall response on olorofim monotherapy was stable; wound closure with complete resolution of IFI was achieved at D322 .1 received oral olorofim (150mg BID x1d loading dose then 90mg BID). Outcomes in the first 100 patients are compared with historical controls (HCs) as well as with expected outcomes in patients with baseline highly active, uncontrolled IFI (HAU-IFI).Patients with limited/no treatment options for proven invasive fungal infection (IFI) or probable pulmonary invasive aspergillosis (IA) using EORTC-MSGERC criteria2  was 47%/42% in IA , 53%/53% , 55%/36% , and 50%/50% . Stable response at D42/D84 predicted extended therapy responses, especially in HAU-IFI of brain and bone . For Coccidioides (n=11) OR was limited to stable due to very slow clearance of fungal serology but clinical response was rapid. Symptoms resolved completely in 18% (2/11) by D84 vs 3% (1/29) by D1523 in comparable HCs with poorly controlled extrapulmonary Coccidioides infection; similar trends were seen for other response measures.All-cause mortality in IA at month 3  was 17/53  for olorofim vs. 40/46  in HCs given either no therapy or azole monotherapy for azole-resistant IA. Successful EORTC-MSGERC overall response3, considering stable in overall success if often appropriate when assessing responses in non-IA mould IFI.Olorofim is a novel oral antifungal with activity against a wide range of mould infections which are difficult to treat. Compared with relevant HCs or expected outcomes for HAU-IFI, olorofim has a positive benefit-risk profile in a well-defined population of patients with limited/no treatment options. As noted previouslyReferences:1. Donnelly CID 2020; 71:1367–762. Segal CID 2008; 47:674–833. Perfect Mycoses 2018: 61:420Johan A. Maertens, MD PhD, F2G Ltd: Advisor/Consultant|Gilead Sciences Ltd: Advisor/Consultant|Mundipharma: Advisor/Consultant|Pfizer Inc: Advisor/Consultant Paul E. Verweij, PhD, Gilead: Grant/Research Support Emma L. Harvey, MBBS, F2G Ltd: Stocks/Bonds Aaron Dane, MSc, Amplyx: Advisor/Consultant|AN2 therapeutics: Advisor/Consultant|Artizan: Advisor/Consultant|Cidara: Advisor/Consultant|ContraFect: Advisor/Consultant|Correvio: Advisor/Consultant|Davolterra: Advisor/Consultant|Destiny Pharma: Advisor/Consultant|Entasis: Advisor/Consultant|F2G Limited: Advisor/Consultant|GSK: Advisor/Consultant|Humanigen: Advisor/Consultant|Kymab: Advisor/Consultant|Modis: Advisor/Consultant|Orca: Advisor/Consultant|Pfizer: Advisor/Consultant|Phico: Advisor/Consultant|Pled Pharma: Advisor/Consultant|Rare Thyroid: Advisor/Consultant|Roche: Advisor/Consultant|Scynexis: Advisor/Consultant|Sinovent: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant|Transcrip: Advisor/Consultant|Venatorx: Advisor/Consultant Daniela Zinzi, Infectious Diseases Specialist, F2G: F2G employee|F2G: Stocks/Bonds John H. Rex, MD, Advent Life Sciences: Operating Partner|Advent Life Sciences: Ownership Interest|AMR Action Fund: Advisor/Consultant|AstraZeneca: Stocks/Bonds|Basilea Pharmaceutica: Advisor/Consultant|Bugworks Research, Inc.: Advisor/Consultant|F2G, Limited: Employee|F2G, Limited: Stocks/Bonds|Forge Therapeutics: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|Pfizer Pharmaceuticals: Honoraria|Sumitovant: Advisor/Consultant Sharon C. Chen, PhD MBBS, F2G PTy Ltd: Grant/Research Support|MSD Australia: Grant/Research Support.


A tunable graphene absorber, composed of a graphene monolayer and a substrate spaced by a subwavelength dielectric grating, is proposed and investigated. Strong light absorption in the graphene monolayer is achieved due to the formation of embedded optical quasi-bound states in the continuum in the subwavelength dielectric grating. The physical origin of the absorption with high quality factor is examined by investigating the electromagnetic field distributions. Interestingly, we found that the proposed absorber possesses high spatial directivity and performs similar to an antenna, which can also be utilized as a thermal emitter. Besides, the spectral position of the absorption peak can not only be adjusted by changing the geometrical parameters of dielectric grating, but it is also tunable by a small change in the Fermi level of the graphene sheet. This novel scheme to tune the absorption of graphene may find potential applications for the realization of ultrasensitive biosensors, photodetectors, and narrow-band filters. Absorbers possess a wide range of applications, including radar stealth, infrared detectors, thermophotovoltaic cells, and thermal emitters. According to their spectral bandwidths, the absorbers can be classified as broad-band absorbers and narrow-band absorbers –4. In geTunable absorption is interesting regarding many potential applications. There are generally two ways to achieve tunable absorption. One is to change the structural parameters and the other is to add tunable materials, such as phase change materials, graphene, or liquid crystals. Among them, graphene has attracted much attention in optics and optoelectronics –34. As aIn this paper, motivated by the investigation in , a tunabd, the width w, and the thickness h. The refractive indices of grating and substrate are nh and ns, respectively. TM polarized  monochromatic plane waves are incident from the substrate at an angle θ. In our simulation, we set d = 3.3 μm, w = 2.31 μm, h = 3.5 μm, nh = 3.48, ns = 1.45, and θ = 0.1°.The surface conductivity of graphene has intraband and interband contributions and is described by:intra and σinter are the intraband and interband conductivity, respectively. In the mid-infrared wavelength region considered in this work, the Fermi level is greater than half of the photon energy, that is, ℏω < 2Ef. Thus, the intraband contribution will dominate the graphene conductivity as the interband transitions are negligible due to Pauli blocking. Therefore, the conductivity of graphene can be approximately expressed by the Drude-like surface conductivity σintra as follows [Here, σ follows –56:Ef is the energy of the Fermi level, ω is the angular frequency, e is the elementary charge, and τ is the carrier relaxation lifetime.where ℏ is the reduced Planck’s constant, In our simulation, the permittivity of the graphene monolayer is described by:0 is the relative permittivity of vacuum, and hg is the thickness of the graphene, which is assumed to be 0.34 nm. Throughout this work, we assume τ = 0.1 ps. The Fermi level is initially considered to be Ef = 0.3 eV, and its influence on absorption spectra will be analyzed latter.where εA(λ) are obtained from reflection spectra R(λ) and transmission spectra T(λ) through A(λ) = 1 − R(λ) − T(λ), where, R(λ) and T(λ) are calculated by employing the rigorous coupled wave analysis (RCWA) method [Q = λ/Δλ, where λ is the resonant wavelength of the absorption peak and Δλ denotes the full width at half maximum of the peak.Based on the parameters mentioned above, we calculated the absorption spectra shown in ) method –58. CleaHy and Ex are antisymmetric with respect to the y–z plane, as illustrated in z-axis direction will be forbidden as the symmetry of field inside the grating is mismatched with the external field distributions [z-axis direction is also forbidden because only zero-order radiation is permissible for light under normal incidence owing to the subwavelength unit cell of this structure. Therefore, the radiation mode will be confined in the dielectric grating, which results in large electric field intensity enhancement and concentration inside the grating, as presented in Ploss/dV = 1/2ε0ω·Im (ε(ω))|E|2, where Im(ε) denotes the imaginary part of relative permittivity and E is the electric field. Thus, the strong electric intensity enhancement inside the dielectric grating will boost light absorption in the graphene monolayer when it is attached on the grating. The enhanced absorption in the graphene monolayer is attributed to the excitation of optical quasi-BICs of radiation modes.To examine the physical mechanism of this phenomenon, we illustrate the distributions of the electromagnetic field at the resonant wavelength in ibutions . At the −2 in Q = λpeak/|λPeak − λdip| [−2, indicating the formation of BICs in the proposed structure [To confirm that the absorption originates from quasi-BICs, we show the simulated zero-order transmission spectra of the structures without graphene monolayer for angles of 0°, 0.1°, 0.5°, 1.0°, 1.5°, and 2.0° in  − λdip| . It is ftructure .1 = 7908.03 nm and λ2 = 7444.8 nm. Obviously, the peak absorptions of λ1 and λ2 are in the direction of 0° and 16.3°, respectively. In addition, their corresponding angular widths are about 0.22° and 0.086°, respectively, which are ultranarrow angular bandwidths. Therefore, the proposed absorber possesses excellent spatial coherence as the inverse relationship between coherence length and its angular width [Subsequently, we examine the spatial directivity of the absorber. In ar width . Usuallyar width . The sped from 3.2 to 3.4 μm results in the shift of the resonant peak to longer wavelengths. This trend is similar to the change of d when h or w are increased. Moreover, the absorption remains almost unchanged with the change of geometric parameters. It is worth noting that the absorption is more sensitive to the change of w than to that of d and h. In general, the ultrasharp absorption can be maintained with a large tolerance regarding the geometric parameters, which is beneficial for real-life fabrication.As mentioned above, the absorber has an ultrasharp absorption profile due to the formation of optical quasi-BICs, indicating that the absorption is sensitive to a change of the geometric parameters. Therefore, the geometric tolerance should be precisely controlled inside a certain range during fabrication. We investigate the influence of geometric parameters on the absorption spectra so as to provide a useful guidance for practical fabrication. The results are shown in Ef increasing from 0.1 to 0.5 eV. In addition, the corresponding resonant absorption increases first and then decreases again. Thus, the ultranarrow absorption could be dynamically controlled through changing the Fermi level without re-designing and re-fabricating the structure, which should be attractive for real-life applications.As the surface conductivity of the graphene sheet is proportional to the Fermi level , a changAlthough the theoretical Q-factor of BICs for the dielectric resonant gating is nearly infinite, the practical Q-factor with the fabricated grating only has a large finite value. As clearly shown in In summary, an active graphene absorber, consisting of a graphene monolayer and a substrate spaced by a dielectric grating, is proposed and investigated. The absorber exhibits an absolute absorption of more than 50% using a graphene monolayer, which is attributed to the extremely high field enhancement in graphene associated with embedded bound states in the dielectric grating. The electromagnetic field distributions confirm the physical origin of this phenomenon. The proposed absorber has an ultranarrow absorption profile with ultrahigh Q-factor and high spatial directivity, which enables the use as a thermal emitter with high spatial directivity. We also found that the spectral position of the absorption peak can be changed without degrading performance by adjusting the geometrical parameters. This indicates a large geometric tolerance, which is advantageous for fabrication. More importantly, the operating wavelength can be tuned by only a small change in the Fermi level, which is particularly attractive as the absorption properties can be electrically tuned without re-fabricating the whole structure. The results may find potential applications for the realization of high-performance graphene-based electrically tunable active devices including ultrasensitive biosensors, detectors, and perfect filters.


While cobaloximes have been protagonists in the molecular (photo)catalytic hydrogen evolution reaction field, researchers originally shed light on the catalytically active metallic center. However, the specific chemical environment of cobalt, including equatorial and axial ligation, has also a strong impact on the catalytic reaction. In this article, we aim to demonstrate how pyridine vs. imidazole axial ligation of a cobaloxime complex covalently grafted on graphene affects the hydrogen evolution reaction performance in realistic acidic conditions. While pyridine axial ligation mirrors a drastically superior electrocatalytic performance, imidazole exhibits a remarkable long-term stability. The Raman spectra of exfoliated graphene, [Co]-pyr-graphene and [Co]-imi-graphene  under Nrivative a. On therivative a. In ordrivative b confirmrivative a, with sThe TGA graphs of pyridine/Co(III) and imidazole/Co(III) compounds are shown in 6 oxygen-free, dry DMF /Co(II), Co(II)/Co(I) and Co(IV)/Co(III) redox couples, respectively (+ corresponding to Co(III)/Co(II), Co(II)/Co(I) and Co(IV)/Co(III) redox couples, respectively  via square wave voltammetry recorded in 0.1 M TBAPF dry DMF , Table 1ectively a 23]. I. I6 oxygectively b. Due tographene a,b. In A1/2 of Co(II)/Co(I) reductive couple of their molecular analogues. Especially, the easier Co(II)/Co(I) reduction, revealed by the positive shift on the E1/2 for both [Co]-pyr-graphene and [Co]-imi-graphene, is in line with the higher electron donation ability channeled by graphene.The oxidation from Co(III) to Co(IV), being close to the upper limit of the electrochemical window of DMF, was also not visible in functionalized materials, which is the case for most studies on molecular cobaloximes ,21. HoweCombination of local scanning transmission electron microscopy (STEM) studies and macroscopic X-ray photoelectron spectroscopy (XPS) analyses constitute perfect approaches for getting important information on structural and chemical composition, even at subnanometer scale, of complex systems. We performed such studies of [Co]-pyr-graphene and [Co]-imi-graphene. Further electron-energy loss spectroscopy (EELS) analyses confirm these findings . Further2SO4 electrolyte. 2 (10η)  -imi-graphene’s  and more than 300 mV lower compared to exfoliated graphene’s . To our pleasant surprise, [Co]-pyr-graphene and [Co]-imi-graphene differ significantly, with the former being drastically superior. This is confirmed also based on the inherent kinetics of each material as reflected by the Tafel analysis (ct) value of 116 Ω for [Co]-pyr-graphene was lower than that of 133 Ω for [Co]-imi-graphene albeit higher than exfoliated graphene . The lower Rct value accounts for a faster Faradaic process and, therefore, superior HER kinetics [ct for both modified materials compared to graphene can be probably attributed to the disruption of the vast sp2 graphene lattice or else modulation of its electronic structure due to surface covalent modification and immobilization of cobaloxime. Still, the pyridine analogue surpasses kinetically the imidazole analogue, validating the rest electrocatalytic parameters   as activanalysis b. In fackinetics . The higrameters .2  of both is faintly enlarged, mirroring vaguely inferior kinetics after 10,000 catalytic cycles. The plausible protonation of the imidazole ring in the highly acidic pH conditions, decreases the Lewis basicity of imidazole ligand, resulting in less electron-donating activity, thus difficult protonation of the Co-H intermediate species that eventually releases H2 [In contrast, durability studies reflect a different point of view. The LSV polarization curves of the graphene materials after 10,000 catalytic cycles are presented in 2 . Evidentime ring  that refime ring , this reeases H2 ,29. ThisIn summary, despite the prima facie evidence, axial ligation of the cobaloxime functionalized graphene plays a major role in the HER electrocatalytic process. Pyridine axial ligand induced a better electrocatalytic activity, which was also confirmed kinetically. In contrast, imidazole moiety was found to equilibrate long-term and resist any deactivation upon extensive cycling. Our results highlight the importance of the primary axial coordination sphere substituents to cobaloxime complexes utilized as HER electrocatalysts and provide a different point of view to researchers engaging in the surface engineering of 2D nanomaterials as electrocatalysts.


The feasibility of realizing largermembranes with diameters of 300 μm and even higher compliancesis shown, although these have lower yields. We present a process forlocally growing graphene on a silicon wafer and realizing suspendedmembranes of patterned graphene across through-silicon holes by bulkmicromachining and sacrificial layer etching, such that no transferis required. This transfer-free method results in a 100% yield formembranes with diameters up to 155 μm on 132 fabricated drums.The device-to-device variations in the mechanical compliance in theaudible range (20–20000 Hz) are significantly smaller thanthose in transferred membranes. With this work, we demonstrate a transfer-freemethod for realizing wafer-scale multilayer graphene membranes thatis compatible with high-volume manufacturing. Thus, limitations oftransfer-based methods for graphene microphone fabrication such aspolymer contamination, crack formation, wrinkling, folding, delamination,and low-tension reproducibility are largely circumvented, settinga significant step on the route toward high-volume production of graphenemicrophones.During the past decadesmicro-electromechanical microphones havelargely taken over the market for portable devices, being producedin volumes of billions yearly. Because performance of current devicesis near the physical limits, further miniaturization and improvementof microphones for mobile devices poses a major challenge that requiresbreakthrough device concepts, geometries, and materials. Grapheneis an attractive material for enabling these breakthroughs due toits flexibility, strength, nanometer thinness, and high electricalconductivity. Here, we demonstrate that transfer-free 7 nm thick multilayergraphene (MLGr) membranes with diameters ranging from 85–155to 300 μm can be used to detect sound and show a mechanicalcompliance up to 92 nm Pa Todorović et al. demonstrated a membrane witha 5 mm membrane diameter composed of 300 layers of chemical vapordeposition (CVD) graphene with a 10 dB higher sensitivity than commercialnickel-based microphones.4 Woo et al. realizeda high-sensitivity microphone for hearing aids with a heterostructuremembrane composed of 0.6 μm of graphene and 3 μm of PMMAon a 2.65 mm diameter membrane.5 Wittmannet al. reached almost similar performance as commercial silicon-basedcapacitive microphones using 15× smaller membranes (diameter2r = 40 μm) made by only few-layer graphene.6 The high performance is mainly due to graphene’shigh flexibility, low tension, and low out-of-plane stiffness, whichresults in large displacements in response to sound pressure. Significanteffort has been made to improve the process to realize free-standinggraphene by transferring the material to the target substrate by acarrier polymer with wet, dry, or semidry methods.7 The introduction of the inverted floating method (IFM)by Lee et al. and Akbari et al. helped fabricate large free-standingCVD graphene up to 2r = 500–750 μm.9 A combination of hydrogen bubbling transfer with thermal annealingby Chen et al.10 resulted in a suspendedfive-layer graphene membrane with a diameter of 1.5 mm. Carvalho etal. developed an anthracene sublimation assisted process achievingten layers of CVD graphene suspended over 4 mm openings.11 Recently, six-layer graphene and 450 nm of PMMAwere suspended over a closed cavity by HF vapor release (VHF) of thesacrificial layer after the graphene transfer.12 The dry release avoids liquids that usually introduce capillaryforces that pull down the suspended part introducing ruptures or breaks.13 Moreover, exposing the graphene to wet HF mightalso lead to unwanted delamination of the graphene from the substrate.14 However, despite the very high aspect ratiosand high crystallinity of the demonstrated free-standing membranes,the mentioned works do not provide a clear route toward industrializationof the devices because the transfer-based methods employed are noteasily scalable toward high-volume wafer-level fabrication since nocommercial equipment for transferring suspended graphene is available,and current methods often suffer from low yield, polymer contamination,cracks, and folding, leading to adhesion issues, especially for nonplanarizedtarget substrates.7 This work proposesan alternative approach to overcome part of the previous limitationswith a wafer-scale transferless method where multilayer graphene (MLGr)drums are grown and released on the same substrate. The method ispotentially less prone to contamination and degradation of the membranesand less sensitive to topography, allowing it to be applied on nonplanarizedsurfaces. The realized multilayer graphene drums made by using thisapproach reach a peak mechanical compliance of ≈92 nm Pa–1 for 300 μm membranes with a yield of 18% andof ≈9 nm Pa–1 with a 100% yield of functionaldevices with diameters ranging between 85 and 155 μm. A studyof the relation between the membrane diameter (2r = 85–300 μm) and the mechanical compliance, for morethan 50 drums, demonstrates a good tension uniformity since it followsthe expected quadratic dependency.15Inthe past 10 years, suspended graphene has attracted the interestof scientific and engineering communities due to the possibility ofusing its unique properties for sensor devices with novel functionalityand improved performance like microphones, pressure, gas and Hallsensors.17 ML-graphene (MLGr) is preferred here due to its higher mechanicalstrength that is required to realize membranes of sufficiently largediameter for microphone applications. Because the synthesis of thegraphene is performed at 935 °C, all the materials are selectedto have a sufficiently high melting point and mechanical stabilityduring graphene CVD. Thermal SiO2 and LPCVD silicon-richlow-stress SiNx are stable at these hightemperature and show an etch selectivity of 40:1 to the vapor HF basedon preliminary results and previous works on Si MEMS.19 The SiNx layer is used as clamping supportlayer all around the edge of the graphene membrane and is also usedto protect certain parts of the SiO2 from being etchedduring the silicon backside deep reactive ion etch (DRIE) and vaporHF sacrificial layer SiO2 release etch (The deviceprocess design utilizes multilayer (ML) transfer-free graphene andvapor HF compatible materials to ensure the structures survive thesacrificial layer etch. Prepatterned Mo is used as a catalyst seedlayer to locally synthesize the graphene on Si substrates along thesame procedure described in earlier studies.ase etch 1.2Cl2 315 sccm/NH3 85sccm) is deposited at 850 °C on top of 1 μm thermal oxideon a 100 mm silicon p-type wafer. The SiNx is dry-etched in defined regions on the topside and entirely removedon the backside where a PECVD TEOS-based 5 μm is then depositedto work as etching mask for the silicon DRIE as shown 2 chemistry. Because of thenature of the sputtering process, Mo covers all the steps in the topography. Inthis way, the CVD-grown graphene will not suffer from any discontinuities.The positive photoresist is then removed by O2 plasma,and all the remaining residuals are washed in N-methyl-2-pyrrolidone(NMP) with subsequent DI water washing . No polymersor tapes are involved during the final isotropic etching step sincethey might trap HF molecules due to their porous nature, and theycan usually be only removed by aggressive methods such as O2 plasma or other dry-etching chemistry that can damage or removethe suspended graphene. With this proposed approach, a lower temperatureof T > 110 °C can be used to clean all theresidualsthat originate from the LPCVD SiNx growthand vapor HF reaction,21 which is low comparedto the T > 250 °C cleaning step typicallyneededto remove the polymer used to transfer the graphene on prepatternedholes. The low temperature in the proposed approach is advantageousbecause thermal removal of the transfer polymer residuals generallyresults in a lower number of surviving membranes due to thermal expansioncoefficient mismatch of the suspended graphene and the substrate,especially for larger membranes.9A layer of 110 nm LPCVD silicon-richlow-stress (SiH22 Acoustic actuation at a sound pressure level of 1 Pa (≈ 94dB SPL) is used to test the fabricated membranes.The input sound pressurefrom a speaker is measured with a reference microphone (SonarworksXREF20) placed next to the sample. A Moku:Lab hardware platform fromLiquid Instruments records the signal detected by the reference microphone,the mechanical frequency response of the graphene membrane as detectedby using a Polytec vibrometer focused at the center of the membrane,and the output signal of the speaker. After proper correction forthe corresponding sensitivities of the vibrometer controller and referencemicrophone, the mechanical compliance is obtained from the ratio ofthe two signals received by the Moku:Lab.2/MLGr heterostructure (before HF etch of theSiO2) is optically inspected by a 3D laser scanning confocalmicroscope on more than 100 drums. The graphene is observed to displayout-of-plane deformation  is relatively far from theory, which is attributed to thepresence of higher buckling modes.26 Oncethe SiO2 is etched, the graphene restores its originalflat shape in the suspended region by adhesion to the unetched siliconsubstrate along its circumference . We verify its flatness by measuring the step height betweenthe surface of the Cr/Au electrode and the Si surface of the suspendedMLGr . They may negatively affect the grapheneintegrity creating randomly distributed tears and localized stress.During the vapor HF, handling, and storing they might be a sourceof crack propagations leading to final membrane breakage. Gas pressureon the membrane during handling and storage might also play a roleand account for the yield reduction in the larger membranes. Thisyield reduction might be mitigated in future processes by tuning thestress and thickness of the oxide layer or by using strain compensationmeasures like suspending the MLGr from a SiNx frame that generates tensile stress.27Whereas this model captures the deflection of the small membranesquite well, the deflection mference S1b. We vmference S1b. We v+ laser maintained at 5 mW to minimizeany possible damages by laser heating. A 100× objective witha numerical aperture of 0.9 is used, giving a spot size of about 696nm. The graphene properties are mainly characterized by two Ramanbands: The first is the G band, which is characteristic of all thegraphitic sp2-type structures and typically centers at1580 cm–1 when the material is in a stress and doping-freestate. The second band is the 2D band, which is centered at 2700 cm–1 and mainly gives information about the number andstacking order of the layers. In 17 This increased defectivitysource is mainly attributed to the lift-off step where N-methylpyrrolidone (NMP) is used for the Cr/Au electrode fabrication.The graphene on Mo is exposed for 40 min at 65 °C with a finallow-power ultrasonic bath of 90 s to strip the cross-linked photoresist(PR). Intercalation of NMP into the stacked layers and the short ultrasonicbath have probably negatively affected the quality of the material,as already reported in other works.30 We exclude that theDRIE is invasive since the graphene is not exposed to the plasma etchfrom the backside of the wafer and instead faces the tool’schuck. VHF is also not considered a possible defective source becausethe ID/IG ratiodoes not show any significant change after the release  from Cypher Asylum Research is used in semicontactmode for the graphene thickness measurement, and a value of ≈7± 2 nm is found, where the standard deviation of 2 nm representsits nonuniformity as shown by the variations in the line scans in x, the reported AFM thicknessmeasurements are obtained on graphene which is processed with allthe reported steps except the VHF and then wet-transferred in DI wateron a clean thermally oxidized silicon chip. The graphene needs tobe transferred because SiNx is partiallyetched during the Mo patterning and the VHF exposure and can thereforenot be regarded as a flat reference point. The small wrinkles observedin 35x/Si interfaceacts as a clamping support for the suspended graphene.The crystallinity of theMLGr is investigated through a Horiba HR800 Raman spectrometer equippedwith a 514.5 nm Ar release 3b. Upon ded MLGr 3d. These–4 kPa to reduce air damping effects. The samples are actuated by shakingthem with a piezoelectric element below the chip that is actuatedby using a voltage-controlled stage with a 0.5 V sine wave in thefrequency range f = 50–350 kHz where the fundamentalresonance frequency is given by 36n0 is thepretension (N/m) of the graphene, ρ the mass density, and t the thickness of the graphene. In this relation, the contributionof the bending rigidity is neglected since its is estimated to besmall.37 The inspected membranes show fundamentalfrequencies over a range of ≈156–218 kHz for diametersof 2r = 120–155 μm .The firstmode of the resonance frequency is measured by a digital holographicmicroscope (LynceeTec) using a laser with a wavelength of 666 nm anda 10× objective lens. The interference between the reflectedlaser beam from the sample and the reference path provides the intensityand phase of each pixel defining the 3D topography. The measurementsare performed in a chamber connected to a vacuum pump at 105 μm see 4a and ≈9 N/m see 4a. The d3 Far below the resonancefrequency in the linear regime (such that cubic terms in z can be neglected), the membrane displacement z isrelated3 to the sound pressure level ΔP by the equationr for a constantsound pressure level ΔP. The reported mechanicalcompliances of 76 drums shown in –1 for the smaller membranes with 2r = 85–155 μm and ≈43–92 nm Pa–1 for large membranes with 2r = 300 μm. Sm0 = 3 nm Pa–1.Finally, we characterize the acousticmembrane displacement inthe presence of sound at a frequency of 1 kHz at a sound pressurelevel of 94 dB. The compliance or sensitivity in nm/Pa of the fabricatedgraphene membranes is determined optically by using a single pointlaser Doppler vibrometer (LDV) (OFV-5000 Polytec GmbH) at the centerof the membrane. Details of the experimental setup and procedure canbe found in ref  and the n0 are needed to fit the large (2r = 300μm) and small membranes. Large membranes are closer to the analyticalresults obtained with lower pretension n0 = 0.1 N/m, whereas the smaller membranes yield n0 = 0.2 N/m. This could be attributed to a lower pretensiondue to the larger suspended region where membrane sagging might bemore profound. Moreover, the tension is also affected by the grapheneclamping geometry, where for the same diameter of 300 μm thetrampoline shows an even higher mechanical compliance (by a factor1.4) due to lower tension of n0 = 0.07N/m compared to the fully clamped geometry.2 The mechanical compliance of drums with different sizes and geometries,over the entire audible range, is also reported . When comparing the pretension extracted from n0 are obtained as in r = 300 μm by monitoring the motion ofthe graphene membrane using the Polytec vibrometer22 . The output signal from the polytec in response to an arbitrarysound file is recorded with a sampling frequency of 20 kHz to detectthe sound waveform, and the measured trace is then reconverted toan audio file with Python.The graphene data are fit by rge 2r = 00μm andreported S3. When S, defined as open-circuit sensitivity,38 is measured by an electrical read-out. Theoretically, it is equalto the product between the electrical sensitivity Se and the mechanical sensitivity Sm0 contribution by the equation3822 where the input values Se (m V Pa–1 or dB),pretension (N/m), resonance frequency (Hz), the distance membrane–bottomelectrode g0 (m), and Vb (V) are obtained from the reportedworks.43 For most of the presented data , the mechanicalcompliance is indirectly calculated from Vb (bias voltage),resulting in an underestimation of the extrapolated reported mechanicalcompliance.The proposed wafer-scale transfer-freemultilayer graphene performancesare visually compared in r = 85 to 300 μm. Large arrays of graphene drums withdiameters up to ∼155 μm are fabricated with a high yieldof 100% by using a CMOS-compatible process flow without any transfersteps. These graphene membranes are shown to operate as microphones,detecting sound with mechanical compliances as high as 92 nm Pa–1, which is much higher than that of commercial MEMSmicrophones that typically have a compliance of 3 nm Pa–1. The graphene attains this high sensitivity by using a membranearea that is 10 times smaller than that of the MEMS device. This demonstratesthe great potential of graphene for microphone applications. The fabricationroute for trampoline designs offers the possibility to invent andengineer new suspended graphene geometries for realizing very highmechanical compliances at the wafer scale. When integrated with electrodesand read-out electronics, it can enable next-generation, high volume,wafer-scale graphene microphone technologies.With this work, we present an efficient transferlessmethod tofabricate wafer-scale graphene drums with diameters from 2