The discovery of graphene and its unique properties has inspired researchers to try to invent other two-dimensional (2D) materials. After considerable research effort, a distinct “beyond graphene” domain has been established, comprising the library of non-graphene 2D materials. It is significant that some 2D non-graphene materials possess solid advantages over their predecessor, such as having a direct band gap, and therefore are highly promising for a number of applications. These applications are not limited to nano- and opto-electronics, but have a strong potential in biosensing technologies, as one example. However, since most of the 2D non-graphene materials have been newly discovered, most of the research efforts are concentrated on material synthesis and the investigation of the properties of the material. Applications of 2D non-graphene materials are still at the embryonic stage, and the integration of 2D non-graphene materials into devices is scarcely reported. However, in recent years, numerous reports have blossomed about 2D material-based biosensors, evidencing the growing potential of 2D non-graphene materials for biosensing applications. This review highlights the recent progress in research on the potential of using 2D non-graphene materials and similar oxide nanostructures for different types of biosensors . A wide range of biological targets, such as glucose, dopamine, cortisol, DNA, IgG, bisphenol, ascorbic acid, cytochrome and estradiol, has been reported to be successfully detected by biosensors with transducers made of 2D non-graphene materials. The developments in material science are the driving force of technological progress. In addition, it may be strongly argued that the creation of new materials of different dimensionality and functionality is the primary prerequisite for any likely significant breakthroughs to be made. The invention of graphene has unambiguously demonstrated that the properties of two-dimensional (2D) materials can be different and in many ways far superior to those of the bulk counterpart.2/g) 3−/4−. Under optimum conditions, the amperometric signals decrease linearly with the target DNA concentrations ranging from 0.1 pM–1 nM. The detection limit was observed as low as 20 fM with an excellent selectivity, acceptable stability and reproducibility.Huang et al.  reportedThe authors concluded that the good analytical performance is attributed to the synergistic effect of acetylene black and the unique microstructure of CuS nanosheets. This can open up new opportunities for sensitive and selective detection of specific sequence DNA and provide a promising platform for biosensor design for other biomolecular detection .3N4) is a new semiconductor material with p-conjugated graphitic planes formed by the sp2 hybridization of carbon and nitrogen. The prominent feature of this semiconductor is that it demonstrates the electrochemiluminescence (ECL). Probably the first report on the synthesis of g-C3N4 was by Zhang et al. [3N4 nanosheets prepared by a “green” liquid exfoliation route from bulk g-C3N4 in water were investigated. It was found that 2D g-C3N4 demonstrated enhanced intrinsic photoabsorption and photoresponse compared to the bulk g-C3N4. High stability, good biocompatibility, superior physiochemical properties and large surface area have triggered interest in 2D g-C3N4 nanosheets as a material for ECL biosensors. Indeed, it was recently reported for biosensors based on 2D g-C3N4 for the detection of DNA [Graphite-like carbon nitride  is a novel semiconductor material with wide band gap (Eg = 5.2 eV), which makes it almost an insulator. h-BN is usually present in the form of flakes or sheets and has become widely used recently in the fields of electronics, catalysis and sensing. 2D nanosheets of BN consist of alternating boron and nitrogen atoms, representing an extra smooth surface. It has to be noticed that until now, only several applications of h-BN as a biosensor were reported, while most of them are still in the embryonic stage; while even the nanosheets allotropes—nanotubes of BN—were reported as promising nanotransducers for functionalization of biosensitive layers [Hexagonal boron nitride , which is a significant compound involved in many chemical and biological processes. The electrochemical sensor, based on nanocomposites consisting of BN nanosheets and Au NPs, was reported before [2O2 as a byproduct, like glucose or cholesterol [BN was reported for the successful detection of hydrogen peroxide  with green fluorescence, was reported. The sensor was proven to be an efficient platform for cell imaging, due to the nanocomposite’s strong fluorescent intensity, stability, water solubility, ry, etc. .Another type of nanocomposite was made based on h-BN nanosheets and Au nanoparticles as a label and applied for an immunosensor for the detection of interleukin-6 by the fluorescence and electrochemistry approaches. The sensor demonstrated excellent performance, which the authors attributed to the high surface area and morphology for antibodies’ immobilization .2, MoO3, WO3 and ZnO [Another type of inorganic non-graphene 2D material is metal oxides, which have recently stimulated plenty of interest as immobilizing matrixes for biosensor development. Nanostructured oxides of metals, such as zinc, iron, cerium, tin, zirconium, titanium and magnesium, have been found to exhibit interesting nanomorphological, functional biocompatible, non-toxic and catalytic properties . Among t and ZnO ,86, have2 nanosheet as the energy acceptor was proposed by Yuan et al. [2 surface. This resulted in the energy transfer from the fluorophore to MnO2 and the respective quenching of the fluorescence. Exposure of the aptamers with OTA molecules changes the conformation of the aptamers, which reduces the exposure of the nucleobases. As a consequence, the physisorption of the aptamers on MnO2 surface is weakened. Thus, the emission of the fluorophore is expected to be recovered, which enables the recognition and quantification of the target [For the first time, a homogeneous FRET sensing protocol using a MnOn et al. . The bioe target .et al. [in vivo sensing of ascorbic acid (AA) in rat brain. Single-layer MnO2 nanosheets were used for suppressing the fluorescence of 7-hydroxycoumarin. The mechanism for the fluorescence suppression is attributed to a combination of an inner filter effect (IFE) and a static quenching effect (SQE). The combination of IFE and SQE leads to an exponential decay in fluorescence intensity of 7-hydroxycoumarin with increasing concentration of MnO2 nanosheets in solution. Such a property allows optimization of the concentration of MnO2 nanosheets in such a way that the addition of reductive analyte  will to the greatest extent restore the MnO2 nanosheet-suppressed fluorescence of 7-hydroxycoumarin through the redox reaction between AA and MnO2 nanosheets. Compared to the turn-on fluorescent method through first decreasing the fluorescence to the lowest level by adding concentrated MnO2 nanosheets, the method demonstrated here possesses a higher sensitivity, lower limit of detection and wider linear range. Upon the use of ascorbate oxidase to achieve the selectivity for AA, the turn-on fluorescence method demonstrated can be used for in vivo sensing of AA in a simple, but reliable way [Different from those reported for the traditional two-dimensional nanosheets, a sensing mechanism was reported by Zhai et al.  for in vable way .et al. reported a facile surfactant-templated synthetic strategy for water-dispersible nanoplatelets of MnO2 and then established it as a new biosensing platform for probing and recognizing biomolecular interactions in a homogeneous solution. The sensing strategy is based on the attachment of the ssDNA on MnO2, with the DNA strand interacting non-covalently with nano-MnO2 by the van der Waals force between nucleotide bases and the basal plane of MnO2. This platform possesses three excellent features: (i) MnO2 with an excellent dispersibility in water can be synthesized in great force at room temperature and used as a quencher without further processing; (ii) the MnO2-based biosensor is low cost and can finish the biomolecular assay within a few minutes; (iii) the biosensing strategy can be applied to other types of molecular probes by simply changing the sequences of the ssDNA to a specific target [He c target .et al. reported a design of FET, using the 2D molybdenum trioxide (MoO3) material. As a protein model, bovine serum albumin was used. α-MoO3 nano-flakes, with the majority of nano-flake thicknesses being equal to or less than 2.8 nm, were stacked in a nanostructured film, forming the conduction channel. The FET demonstrated impressive response time (≤10 s). The authors explain this due to the high permittivity of the 2D α-MoO3 nano-flakes. It has been concluded that the 2D α-MoO3 system offers a competitive solution for future biosensing applications [Balendhran ications .i.e., bulk or nanostructures. Thus, Vabbina et al. reported label-free, highly sensitive and selective electrochemical immunosensors based on 2D ZnO nano-flakes (ZnO-NFs) which were synthesized on Au-coated substrates using a simple one-step sonochemical approach. Selective detection of cortisol using cyclic voltammetry (CV) is achieved by immobilizing anti-cortisol antibody (Anti-Cab) on the ZnO nanostructures (NSs). 2D ZnO-NFs provide unique sensing advantages over bulk materials. 2D-NSs with a large area in the polarized (0001) plane and a high surface charge density could promote higher Anti-Cab loading and, thus, better sensing performance. Beside a large surface area, ZnO-NSs also exhibit higher chemical stability, high catalytic activity and biocompatibility. The measured sensing parameters are in the physiological range with a sensitivity of 7.74 mA/M with the lowest detection limit of 1 pM, which is 100-times better than the conventional enzyme-linked immunosorbent immunoassay (ELISA). ZnO-NS-based cortisol immunosensors were tested on human saliva samples, and the performance were validated with a conventional (ELISA) method, which exhibits a remarkable correlation. The developed sensors can be integrated with a microfluidic system and a miniaturized potentiostat for point-of-care cortisol detection, and such a developed protocol can be used in personalized health monitoring/diagnostics [Zinc oxide is a semiconducting material with plenty of advanced properties, such as high catalytic efficiency, biocompatibility, chemical stability in physiological environments and low toxicity. It possesses a high isoelectric point (IEP) of about 9.5, which makes it a rather prospective candidate for biosensing applications . 2D ZnO gnostics .p-type conductivity  has been used in many electronic applications and sensors. Such a metal oxide can have many well-defined nanostructures with different dimensionalities, possessing unique electronic and optical properties. For instance, due to the size confinement effect, the 2D CuO has an enhanced optical band gap (gE = 2.15 eV) [et al. [et al. [−1·cm−2, a fast response time of ∼2 s, a relatively wide linear dynamic range of 0.1–4.0 mM, a low detection limit of 50 nM and good anti-interference ability.Copper oxide being a narrow gap semiconductor with 2.15 eV) . Recentl2.15 eV) ,95. Most2.15 eV) ,97. In p2.15 eV) ,97 repor [et al.  designedvs. no band gap in graphene) or bulk crystals (the highest surface-to-volume ratio in 2D). Using the 2D non-graphene materials, the biosensors can be designed for different types, mainly electrochemical  or optical (by quenching the fluorescence or retaining it via aptamers use).It is revealed that the family of 2D non-graphene inorganic materials is undeniably forthcoming for the application as a transducer material in biosensors. This is indirectly proven by the growing research interest, reflected in a rising number of papers during the last few years. The scientific reports clearly demonstrate the certain advantages of 2D non-graphene materials over graphene . It is shown that many different biological agents can be successfully immobilized on the surface of 2D non-graphene materials, providing sensing ability for a wide range of biological targets, as is demonstrated in 2, WS2, VS2, CoS, CuS). Specifically, MoS2 is the most reported non-graphene 2D material in the biosensing area. This may be explained by its several advantages, including comparatively simple synthesis procedure and possibility of direct (CVD) growth. Another important advantage of MoS2 for biosensors is that it has polarized planes, which favors the van der Waals interaction and promotes the biosensitive layers’ immobilization, for both enzyme-based and non-enzyme electrochemical biosensors. The realization of the FET-based biosensing device with MoS2 as a channel results in obtaining a highly sensitive, single-molecule detection compatible sensor. Eventually, the performance/sensitivity of the MoS2-based FET biosensor was reported to be 74-fold better than that one of the graphene-based one. In the optical type of biosensors, MoS2 has high fluorescence quenching ability, good detection limits and fast response time. Via functionalization of MoS2 by aptamers, the optical biosensor demonstrates high sensitivity with a simple design and low cost. Finally, nanocomposites containing MoS2 together with graphene and/or metal nanoparticles were reported to be efficient transducers for the electrochemical type of biosensors of a wide range of analytes.Chalcogenides are the dominant materials among the non-graphene 2D, reported in biosensors’ design  of about 9.5. All the above makes 2D ZnO therefore extremely promising for biosensing applications. This, however, is still compromised by its practical unattainability, which will be an exciting materials researcher’s task for the next few years. Finally, we would like to conclude that the present tendency of growing the 2D materials library will result in the appearance of new candidates, which will definitely join the biosensing area soon.


The ideality factor of the graphene/ZnO nanowire Schottky diode is ~1.7, and the Schottky barrier height is ~0.28 eV without external Vg. The Schottky barrier height is sensitive to Vg due to the variation of Fermi level of graphene. The barrier height increases quickly with sweeping Vg towards the negative value, while decreases slowly towards the positive Vg. Our results are helpful to understand the fundamental mechanism of the electric transport in graphene-semiconductor Schottky diode.Graphene-semiconductor interface is important for the applications in electronic and optoelectronic devices. Here we report the modulation of the electric transport properties of graphene/ZnO nanowire Schottky diode by gate voltage (V The ideality factor of the graphene/ZnO NW Schottky diode is ~1.7, and the Schottky barrier height is ~0.28 eV. Further gate controlling tests demonstrate that the Schottky barrier height is sensitive to the gate voltage, which mainly stems from the high sensitivity of Fermi level of graphene to the gate voltage. The barrier height increases quickly by applying negative gate voltage, while decreases slowly with increase of the positive gate voltage. Our results are helpful to understand the fundamental mechanism of the electric transport in graphene-semiconductor Schottky diode and may be useful for its application in nanoelectronics.via the processes as presented in 2 layer  and G peak (~1589 cm−1) can be clearly observed, while the defect related peak is quite weak. The Raman intensity ratio between the 2D mode and the G mode is ~3, indicating the nature of monolayer graphenesd) of the monolayer graphene as a function of the back gate voltage (Vg) as applying the source-drain voltage (Vsd) of 0.2 V between the electrodes B1-B2. The Isd of graphene can be changed by Vg, suggesting that the Fermi energy level of graphene can be effectively tuned by Vg. The current-voltage (I-V) curve of the graphene/ZnO NW hetero-junction is plotted in The inset in I) passing through the Schottky barrier is determined by the thermionic emission of electrons, which can be written asISAT is the saturation current, q is the elemental charge, η is the ideality factor R is the series resistance, k is the Boltzmann constant, T is the absolute temperature, ϕSB is the Schottky barrier height, A is the interface area of the Schottky barrier, and A* is the Richardson constant A ~ 1 μm2 and the experimental temperature T ~ 300 K, according to η ~ 1.7. The barrier height without gate voltage can be deduced to be ϕSB ~ 0.28 eV. Since the work function for intrinsic graphene is about 4.6 eV and the electron affinity of ZnO NW is about 4.7 eV, the analysis is reasonable according to the experimental results.The formation of Schottky barrier at the interface between graphene and ZnO NW is due to the difference of work function between the two materials. The barrier height can be described as sd-Vsd curves under different Vg were measured. The Isd-Vsd curves between electrodes B1 and A1 of the graphene/ZnO NW hetero-structure under different Vg are presented in g sweeping from −80 V to 0 V, the Isd at the same positive Vsd increases quickly, and then increase slowly with Vg further increasing from 0 V to 80 V. The Isd-Vsd curves at the negative Vsd side exhibit no apparent variation with Vg. Using sd-Vsd curve under different Vg. The variation of Schottky barrier height as a function of Vg was plotted in g from 0 to −80 V, while decreases slowly as varying Vg from 0 to 80 V. This gate voltage modulation of the Schottky barrier height in graphene/ZnO NW hetero-junction is attributed to the linear dispersion relationship of the energy band in graphene, which results in the high sensitivity of Fermi level of graphene to Vg.In order to further investigate the behavior of the Schottky barrier of the graphene/ZnO NW diode, the source-drain Ig. The electron transfer from ZnO to graphene results in the energy band bending near the ZnO NW surface and the formation of a depletion region. The Schottky barrier height is g from 0 to −80 V, the ϕSB of graphene continuously increases, leading to the notable increases of ϕSB .


Pain in arthritis may be experienced in regions outside the affected joint, and hyperalgesia may even be widespread. The spread of pain is usually attributed to mechanisms in the central nervous system. We investigated whether rats with antigen-induced arthritis (AIA) exhibit peripheral changes in skin innervation remote from the inflamed joint.After immunization, unilateral AIA in the knee joint was induced in rats. Intraepidermal nerve fibre density was determined by immunohistochemical staining for protein gene product 9.5 (PGP 9.5) and for nerve fibres expressing calcitonin gene–related peptide (CGRP), substance P (SP), transient receptor potential vanilloid 1 , β-tubulin, and growth-associated protein 43  in paw pad skin and back skin. Cluster of differentiation 11b (CD11b)-positive macrophages and CD3-positive T cells were quantified in skin, and macrophages were quantified in the lumbar dorsal root ganglia. In addition, pain-related behaviour was assessed.Intraepidermal nerve fibre density (PGP 9.5) and the numbers of fibres expressing CGRP, SP, TRPV1, or β-tubulin did not show a significant change in the acute (3 days) or chronic phase (21 days) of AIA compared with control rats that were only immunized. However, paw skin and back skin revealed a significantly higher number of nerve fibres expressing GAP-43 at both the acute and chronic stages of AIA. The skin of arthritic rats in these regions did not contain a greater density of CD11b and CD3 immune cells than the skin of control rats. Enhanced expression of GAP-43 in nerve fibres of the skin was not related to hyperalgesia in the joint, but it accompanied persistent secondary cutaneous hyperalgesia in the skin remote from the inflamed joint.Although the innervation of the skin remote from the joint did not show significant abnormalities of the other nerve fibre markers, the rapid and persistent increase of GAP-43 expression is conspicuous. The data suggest that immune-mediated arthritis is associated with changes in skin innervation remote from the inflamed joint, although the skin is not inflamed, which may contribute to symptoms in nonarticular tissue remote from the affected joint. Chronic joint diseases such as rheumatoid arthritis and osteoarthritis are usually associated with chronic pain in the affected joints. Careful clinical examination has shown, however, that pain is often not restricted to the affected joints. Patients with localized osteoarthritis and rheumatoid arthritis often exhibit allodynia (a reduction of pain thresholds in the innocuous intensity range) and hyperalgesia (increased pain perception on noxious stimulation) in the entire limb , 2. ThesHowever, pain states are not entirely characterized by augmented functional activity in the peripheral and central nociceptive systems. An intriguing finding is the change of the innervation density of diseased joints. Inflamed synovial tissue derived from experimental arthritis and from patients with rheumatoid arthritis showed a significant reduction of nerve fibre density. Some authors reported a reduction of peptidergic sensory afferents –16, wherChanges of innervation density are likely to be caused by local factors in the joint. However, to our knowledge, whether changes of the innervation density in joint diseases are restricted to the affected joint, or whether such changes also occur remote to the afflicted joint, has never been systematically tested. We therefore addressed this question in the present study using the AIA model in the rat, an animal model of monoarticular inflammation usually induced in the knee joint, which reproduces major aspects of clinical rheumatoid arthritis. Rats with AIA show a highly reproducible pathology with well-defined acute and chronic states. Pronounced inflammation of the affected knee joint with local swelling and hypersensitivity, as well as hyperalgesia in areas remote from the inflammatory process , have been described , 20. SpeThe study on AIA was performed on 25 female Lewis rats . All experiments were carried out in accordance with the European Communities Council Directive (86/609/EEC) for the care and use of laboratory animals and were approved by the Thuringian State Office of Food Safety and Consumer Protection, Department of Consumer Protection, Veterinary, Pharmaceuticals (registration number 02-013/08).n = 25) were immunized by two subcutaneous injections of 500 μg of methylated bovine serum albumin  prepared in saline, emulsified with 500 μl of complete Freund’s adjuvant (Sigma) supplemented with 2 mg/ml Mycobacterium tuberculosis strain H37Ra . Fourteen days after the second injection, monoarticular arthritis was induced by a further injection of mBSA  into the left knee joint cavity (n = 20). The five immunized-only rats served as controls.Arthritis was induced as previously described . In brien = 10, acute AIA) or at 21 days  after induction of AIA, the rats were anesthetized by intraperitoneal injection of sodium thiopentone  and killed by transcardial perfusion with heparin-enriched, phosphate-buffered saline (PBS) and 4 % phosphate-buffered formalin.Either at 3 days  as described previously . The difUsing an incapacitance tester , weight-bearing of the inflamed hind limb was assessed as a functional measure of pain-related guarding behaviour. The animals were placed with their hind paws on scales inside a plastic cage, and the weight force on the two scales was measured three consecutive times while the animals sat calmly in the cage after acclimation. From these averaged values, the relative resting weight (expressed as a percentage) of the inflamed hind limb was evaluated [weight of inflamed hind limb × 100 %/(weight of inflamed hind limb + weight of noninflamed hind limb)], as described previously .Primary hyperalgesia at the inflamed knee was assessed with a dynamometer  . At the As previously described , 4, secoAfter the animals were killed, hind paw pad skin , lumbar paraspinal back skin , and lumbar dorsal root ganglia (DRGs) from spinal levels L1–L5  were dissected separately. The specimens were then processed and immunostained as described previously . BrieflyIENFs immunoreactive to PGP 9.5, CGRP, SP, β-tubulin, and GAP-43 were counted in a blinded manner along the length of the tissue section (approximately 3–8 mm) according to the guidelines developed by the European Federation of Neurological Societies (EFNS) . Thus, oCD11b and CD3 immunoreactivity in the dermis and ED1 immunoreactivity in the DRGs were quantified by computerized image analysis. Images were captured using an Olympus DP70 camera mounted on an Olympus BX50 microscope and analysed using Olympus analySIS software. After applying the colour separation for red to blank out the counterstaining, positive immunostaining was highlighted by setting the grey-level detection limit to a fixed threshold, and the area of highlighted immunoreactivity obtained as a percentage of the field scanned. The threshold was kept constant for all specimens analysed that were immunostained with the same marker. For the skin  and DRGs  five and three microscopic fields (magnification × 40) were analysed, respectively, and the mean values were used in statistical analysis.U test (two-tailed). Behavioural changes were examined with the Wilcoxon matched-pairs signed-rank test (two-tailed) and intra- and interobserver correlations as well as IENF correlations with Spearman’s correlation coefficient. Significance was assumed at p < 0.05.Descriptive statistics were created and statistical tests were performed using Prism version 5.03 for Windows software . Group differences for the immunostaining data were assessed using the nonparametric Mann–Whitney p = 0.0059) for the acute AIA vs. baseline values . This pain-related guarding behaviour subsided gradually by day 21 (chronic state)  Fig. .p = 0.0058), demonstrating primary hyperalgesia at the inflamed knee. By day 21, the mechanical thresholds had increased again to values close to baseline . This indicates a trend towards secondary hyperalgesia remote from the inflammation , some extending almost to the stratum corneum  and chronic (p = 0.0007) AIA as compared with controls  with the increase of GAP-43 being significant in acute AIA (p = 0.0159), but not in chronic AIA (p = 0.0952), compared with controls .Intra- and interobserver agreements for the counts of IENFs were highly significant, as verified by correlations  and CD3-immunoreactive (T cells) cells appeared to be of similar density within the three groups examined Fig.  and b. Tp = 0.0007) in acute AIA animals compared with controls on the ipsilateral side .ED1-immunoreactive cells (macrophages) were detected around sensory neuronal perikarya of lumbar DRGs Fig.  – c. Theide Fig.  and on tWe next examined potential correlations between ED1 in the lumbar DRGs and GAP-43–positive IENFs in the paw pad and between ED1 and pain-related behaviour. Figure R = −0.7930, p < 0.0001)   Fig.  and with06) Fig. . Control06) Fig. . This unIn the present study, we investigated whether localized arthritis in the knee joint causes neuronal changes in the skin remote from the joint. Neither overall IENF density nor the numbers of fibres expressing CGRP, SP, TRPV1, or β-tubulin showed a significant change in the acute or chronic phase of AIA compared with control rats. In contrast, the paw and back skin revealed a significantly higher number of nerve fibres expressing GAP-43 in both the acute and chronic stages of AIA. Importantly, the skin of arthritic rats in these regions did not contain a higher density of CD11b and CD3 immune cells than these regions in control rats. However, the lumbar DRGs of both the inflamed and noninflamed sides did exhibit a pronounced invasion of macrophages in the acute stage of inflammation.GAP-43 has received considerable interest in basic as well as clinical neuroscience research because significant changes of GAP-43–positive nerve fibres were identified in human disease states. A reduction of IENF density is considered a hallmark of classical small-fibre peripheral neuropathy. In patients with neuropathy in the course of type 2 diabetes, IENF density was significantly lower than in controls , 31, corGAP-43 is a membrane protein associated with axonal development, axonal regeneration, remodelling, and neuronal plasticity , 37. It Whether alterations of GAP-43 are per se  associated with sensory changes such as pain or sensory abnormalities is currently unknown. In clinical studies, researchers often use changes in the expression of GAP-43 as an indicator of neuronal changes, mostly as an indicator of regeneration or regenerative potential. However, researchers in most studies have not reported whether patients had symptoms such as pain or sensory abnormalities. Interestingly, investigators in one study reported that patients with diabetic neuropathy and pain had higher GAP-43/PGP 9.5 ratios than patients with diabetic neuropathy without pain . HoweverThe present data show some aspects related to this problem. First, in the present experiments, the density of GAP-43–positive IENFs per se did not correlate to hyperalgesia, because at day 3 of AIA the numbers of GAP-43–positive IENFs were scattered from the normal range to enhanced levels but the drop of pain thresholds was pronounced in all animals. Furthermore, at day 21, weight-bearing and primary hyperalgesia at the knee were clearly reversed; yet, all rats exhibited an increase of GAP-43–positive IENFs in the ipsilateral paw at this time point. This suggests that the reversal from a significant pain state in the deep tissue may be associated with an increase of GAP-43–positive IENFs (at least in some areas) see Fig. . HoweverIt is important to note that the behavioural changes in experimental arthritis models correspond to observations in humans. Rats with unilateral arthritis in the knee joint also exhibit local mechanical hyperalgesia at the contralateral healthy knee joint, and they show enhanced sensitivity to mechanical and thermal stimuli at the hind paws , 4. WideWhether humans with rheumatoid arthritis show enhanced GAP-43 expression has not been explored, to our knowledge. However, patients with rheumatoid arthritis do not have significantly altered IENF densities compared with healthy subjects . This daAlthough the sensory consequences of altered GAP-43 expression are unclear, the consensus based on many studies is that neuropathy or local inflammatory changes may be associated with changes in GAP-43 expression and that an upregulation of GAP-43 indicates a regeneration of nerve fibres, whereas a reduction of GAP-43 is associated with a loss of regenerating nerve fibres. The novel finding of the present study is that the GAP-43 expression in nerve fibres was increased in skin remote from an inflamed joint. The present findings are the first, to our knowledge, to indicate that IENFs remote from the joint show changes in arthritis.The question regarding mechanisms which might be involved in the upregulation of GAP-43 in nerve fibres following arthritis in the skin remote from the joint is intriguing. Our data indicate that this process started within the first 3 days of AIA and persisted in some skin regions up to 21 days. In the AIA model, lumbar DRG neurons do not express activating transcription factor 3, a marker for neuronal damage, at the acute or chronic stage . Thus, tIn the present study, we observed, as in two previous studies, a bilateral invasion of macrophages into the lumbar DRGs of both the inflamed and noninflamed sides , 52. ThiWhether the invasion of macrophages into the DRGs is linked to enhanced GAP-43 expression is unknown. The data shown in Fig. On the basis of the present study, we report the novel observation that changes of innervation in arthritis models occur not only in the inflamed joint but also in healthy skin remote from the joint. Because GAP-43 is thought to indicate processes of structural neuronal plasticity, the present findings suggest that arthritis is associated with neuronal changes in skin innervation remote from the inflamed joint. Although the precise role of enhanced GAP-43 expression in mechanisms of pain is not known, the data show that localized immune-mediated arthritis may cause more widespread neuronal alterations in the peripheral nervous system. Such neuronal changes may contribute to long-lasting secondary hyperalgesia in the skin remote from the inflamed joint. Our findings should stimulate research into the regulation and functional importance of GAP-43 and regenerating nerve fibres in arthritis and chronic, widespread pain.


Graphene deposited on various substrates has attracted the attention of the scientific and technical communities for use in a wide range of applications. Graphene on substrates is commonly produced by two types of methods, namely, methods that require a transfer step and transfer-free methods. Compared with methods that require a transfer step, transfer-free methods have a simpler procedure and a lower cost. Thus, transfer-free methods have considerable potential to meet the industrial and commercial demands of production methods. However, some limitations of the current transfer-free methods must be overcome, such as the high temperatures encountered during production, the relatively long manufacturing times, incompatibilities for both rigid and flexible substrates, and an inability to extend the process to other two-dimensional (2-D) atomic crystals. In this work, a room-temperature rubbing method is developed for the rapid transfer-free production of defect-free polycrystalline graphene on rigid and flexible substrates. Starting with inexpensive commercially obtained graphite powder, mono- and few-layer graphene can be fabricated directly on various substrates, with an average production time of less than one minute (from raw graphite to graphene on the substrate). Importantly, this method can be extended to other 2-D atomic crystals. Graphene has attracted intense scientific and technical interest during the past decade, as its extraordinary properties make this material suitable for a wide range of applications, including electronics, photonics, energy, and mechanics12335678989101112131415891011121314158910111213141541718192) and flexible  substrates, and (4) the methods are difficult to extend to other two-dimensional (2-D) atomic crystals.In recent years, transfer-free methods based on different synthesis have been explored, including chemical vapour deposition (CVD) growth with metal catalysts, such as Cu, Ni, Ga, etc.212223242527282930313233343521373839402122232425262728293031323334353637383940Herein, a room temperature rubbing method is developed for the rapid transfer-free production of defect-free polycrystalline graphene on various types of substrates (including both rigid and flexible substrates). Starting with low-cost commercially available graphite powders, mono- and few-layer graphene were directly fabricated with an average production time of less than one minute (from raw graphite to graphene on substrates). Importantly, this rubbing method can be extended to other 2-D atomic crystals. Thus, this process has great potential to meet a number of industrial and commercial demands: it is more likely to produce polycrystalline films than the expensive single-crystalline films242518222719171257114428352) and flexible  substrates instead of only being suitable for flexible substrates; (2) both mono and few-layer graphene can be produced instead of just few-layer graphene; (3) the average time from raw graphite powders to final graphene films is reduced from approximately 10 minutes to less than one minute; (4) the procedures are more environmentally friendly because none of the auxiliary materials are discarded; and (5) importantly, the advantages of the previous rubbing method are maintained, including room temperature and low-cost production, together with the capability of being extended to other 2-D atomic crystals.This rubbing method is an important improvement over our previous methods46All of the auxiliary materials, including the poly (PET) films, the polished silicon (Si) wafers, and, most importantly, the reusable surfaces that are built on the polishing sandpapers, are reusable. The surface morphologies of the auxiliary materials are given in The reusability of the auxiliary materials means that we only needed to complete the sandpaper-rubbing see  and doubAccording to our experiments, these production cycles could continue for more than 20 rounds (commonly 22 to 34 rounds). If we count the rounds as 20, then the total time is 10 + 9 × 20 = 190 min, and the total sample number is (10 to 20) × 20 = 200 to 400. Therefore,1 sample only takes 0.475 to 0.95 min, in other words, within one minute.2) as rigid substrates, whereas PET, polyethylene (PE) and polyurethane (PU) were employed as flexible substrates. All of the chosen substrates have smooth surfaces (surface roughness within 1 nm). The results of graphene on different substrates are presented in In this work, we chose a Si wafer and quartz glass -type defects577425051The elemental purity of the graphene is another important feature to characterize the quality of the produced graphene. In this work, energy dispersive spectroscopy (EDS) was used to detect the different elements present in our graphene sample. The result  reveals (1) How many samples can a reusable surface produce? (2) If possible, then how can the reusable surface be restored for further production?Cyclic operability is one of the main advantages of the proposed method. There are two important issues: th sample on, relatively large differences in the macro-performance (a considerably higher resistivity and higher transparency) and significant changes in the micro-morphology  and the micro-morphology . For example, for 40 s of soft-contact-rubbing, the number is 400/40 = 10, whereas the number of samples increases to 400/20 = 20 for 20 s.P), friction speed (V), and friction time (t). t was selected as the core parameter to be adjusted for the following reasons:(1) Under industrial conditions, t is easier to adjust and control than P and V. (2) Relatively higher P and V are favourable to improve the production efficiency; however, P·V has a direct relationship with the power requirements of the equipment, and such power is limited. Thus, only a relatively small adjustment range is possible for P and V. Consequently, t is the best parameter to describe the controllability and cyclic operability of the method.During each rubbing step, there are three important parameters that impact the controllability: friction pressure : the initial rubbing uses PET as the smoothing material and is followed by smoothing with a polished Si wafer. The impacts of smooth-rubbing-time and smoothing materials (PET or Si) on the number of deposited graphene layers are compared in Control over the number of graphene layers that are deposited is the other important parameter. The layer numbers were obtained from thickness results of AFM tests . These results indicate that the rigid humidity sensor can be used at a relatively high temperature, whereas the PET humidity sensor has the advantage of high flexibility during operation.Polycrystalline grain boundaries can have a strong influence on the properties of graphene films, and also allow the preparation of materials with novel properties7425051ency see . After pency see . The reaThe influence of the graphene sample size on its properties is crucial for industrial and commercial purposes. Notably, the results in 2), tungsten disulfide (WS2), etc.In recent years, 2-D atomic crystals have been explored extensively, and examples of such crystals include those from hexagonal boron nitride (h-BN)1561565455562 and WS2) produced on different substrates by the rubbing method contained within. SEM images of the raw materials are given in 2 substrates are given in 2 atomic crystals, which form a film with individual crystals on a scale of several micrometres. 2 and monolayer h-BN, which were transferred from SiO2 to TEM grids. 2 atomic crystals on a SiO2 substrate.The results showing 2-D atomic crystals on SiOA1g) peaks in the Raman spectra exhibit clear red shifts: approximately 2 cm−1 for few-layer MoS2 and approximately 5 cm−1 for monolayer MoS2. In addition, blue shifts of −1 and approximately 2 cm−1 for few-layer and monolayer MoS2, respectively. Such results were consistent with results from the literature on Raman spectra of bulk MoS2 and MoS2 atomic crystals15455562 atomic crystal flakes. 2 atomic crystal on Si with thicknesses of approximately 1.06 nm.The results of 2-D atomic crystals on Si are given in 2 atomic crystals on PET. 2 on PET that presents atomic crystals on a scale of several micrometres, similar to the case of MoS2.The results of 2-D atomic crystals on flexible PET substrates are given in 2 and WS2 atomic crystals on Si, and just like graphene, most of these atomic crystals are monolayer and bilayer. The similarities between 2 atomic crystals/SiO2 sample. While the similarities of 2 atomic crystals on PET.The controllability and cyclic operation of the method as applied towards 2-D atomic crystals are shown in The rubbing procedures involve the wear processing of the sandpaper surface, e.g., during the double-smoothing-rubbing step, the surface of the sandpaper is worn by PET and the polished Si wafer, while the soft-contact-rubbing step results in the sandpaper’s surface being worn by different substrates. Thus, classical friction and wear theories can be applied to explain the mechanisms behind the rubbing procedures.According to the adhesive wear mechanismDuring the early stages, the rates of wear (d’) on sandpaper’s surface is proportional to pV. Because a certain pV value is already chosen, d’ is approximately constant at the beginning of the soft-contact-rubbing step. Thus, the amount of wear on the sandpaper’s surface increases with rubbing time (t), as does the amount of graphene transferred to the substrates.ad) can be considered proportional to the friction coefficient, as described in Equation According to Archard’s viewThus, at a later stage of the soft-contact-rubbing, the rate of wear (d’) on the sandpaper’s surface is decreased, because graphene that was already transferred to the substrates would decrease the friction coefficient between the sandpaper and the substratesTherefore, a polished Si wafer is chosen because it exhibits a similar surface roughness to PET and has a much higher hardness. According to Rabinowicz’ view on wearThree additional processing conditions  were carried out. Condition 1replaces the initial smoothing material (PET) in the double-smoothing-rubbing step with a polished Si wafer. Condition 2 replaces the second smoothing material (Si) in the double-smoothing-rubbing step with PET. Condition 3 changes the sequence of the double-smoothing-rubbing step .For Condition 1, the smooth region did not increase significantly as the rubbing time increased compare  even thoFor Condition 2, as described in Similar results were obtained under Condition 3 as under Condition 2  at room temperature by a rubbing method. This highly efficient and low-cost method used inexpensive commercial graphite as a raw material. Mono- and few-layer graphene films were fabricated directly on various substrates with an average production time of less than one minute. The size of the deposited graphene flakes was several to tens of micrometres. The graphene was characterized as having a high elemental purity, with defects consisting primarily of boundary (or edge) types. The rubbing method displayed good controllability of the graphene-covered area and of the number of graphene layers on the substrates. The graphene films produced by this method performed well in applications, such as humidity sensing, transparent heating, and strain sensing, thus demonstrating the potential industrial and commercial value of the technique. Furthermore, this rubbing method can be extended to other 2-D atomic crystals.2) glasses  and PET films were used as substrates  and WS2  powders are needed as raw materials for other 2-D atomic crystals.Poly (PET) films  were needed as initial smoothing material (light gray piece in All of the rubbing steps shared the following characteristics: (1) The rubbing action can be described as “revolution without self-rotation”. The rubbing diameter was 0.5 cm, and the rubbing rate was 200 rpm. (2) A commercial rubber  was needed to apply the appropriate pressures. It was affixed to the rubbing equipment, as shown in The commercial raw graphene powder was rubbed between two pieces of polishing sandpaper  by applyAfter this rubbing step, the polishing sandpaper surface would be covered by graphite sheets or other 2-D sheets  with a commercial rubber, the target substrate was rubbed with the reusable surface by applying a soft pressure (0.5 MPa for rigid substrates and 0.1 MPa for flexible substrates) for 20 to 40 s. This rubbing process fabricated the final samples .As shown in As shown in Initially, a proper amount of graphite or other 2-D raw powder was added and then rubbed between the two PET smoothing materials  by applying a soft pressure (0.1 MPa) for 100 s.Then, we rubbed the reusable surface on the PET smooth material by applying a soft pressure (0.1MPa) for 100s. The PET smoothing material can be reused for the next restorative rubbing step. From our experiments, the PET smoothing materials can be reused 20 times.Finally, we affixed the polished Si wafer (after a one-minute ultrasonic cleaning and drying) to the commercial rubber, and we rubbed the reusable surface on the Si by applying a soft pressure (0.2 MPa) for 200 s. The Si smoothing material could be reused for the next restorative-rubbing step, following the cleaning step described above. From our experiments, the Si smoothing materials can be reused more than 100 times.After the above three rubbing steps, the reusable surface was ready for another cycle.2 substrates) were characterized by TEM (JEM-2100F) after transferred onto TEM grid, and the elemental purity of the graphene was detected by EDS. The sizes and distribution of 2-D atomic crystals on SiO2 substrates were observed by optical microscopy (XSP-35). The morphology of graphene and other 2-D atomic crystals on PET substrates and the morphology changes of polishing sandpapers’ surfaces were characterized by SEM (Sirion 200 and Nova NanoSEM 450). Sheet resistance and optical transparency measurements of flexible transparent conductive films (graphene/SiO2 and graphene/PET samples) were taken by Four-probe tester (RTS-8) and UV-Vis Spectra photometry (Lambda 35), respectively.Raman spectra of graphene and other 2-D atomic crystals on Si substrates were characterized by 514 nm Raman spectrometry (INVIA), and the 10 μm × 10 μm area Raman mapping images were obtained from Raman laser whose spot size is 1 μm × 1 μm was moved by 1 μm. The thicknesses of graphene and other 2-D atomic crystals on Si substrates were tested by AFM . The edges of monolayer graphene and other 2-D atomic crystals (peeled from SiO2 and graphene/PET in a pre-defined pattern. The humidity sensing behaviours were tested in a constant temperature and humidity incubator (SPX-160B) at a constant temperature of 300 K while the relative humidity was changed from 30% to 90%.A 30 s soft-contact-rubbing was chosen for humidity sensing. The sensors were fabricated by printing silver pads (3 cm × 0.25 cm) onto 3 cm × 3 cm sized graphene/SiO2 and graphene/PET in a pre-defined pattern. A polycarbonate (PC) film was used as an insulating protective layer for security. The alternating current (AC) working voltage was provided by an adjustable regulated AC power supply. The heating temperature was measured using an infrared thermometer.A 40 s soft-contact-rubbing was chosen for transparent heating. The heaters were fabricated by printing silver pads (6 cm × 0.25 cm) onto 6 cm × 6 cm graphene/SiOFor strain sensing, a 25 s soft-contact-rubbing was chosen. The sensors were fabricated by printing silver pads (12 cm × 0.25 cm) onto 12 cm × 12 cm sized graphene/PU in a pre-defined pattern. The strain gauge factors were calculated by testing the resistivity changes under strain-on/off conditions. The strain was performed and measured by a strain equipment made by ourselves. In this study, “strain off” means 0% strain (without elongation), and “strain on” means approximately 3% strain (with elongation as approximately 0.36 mm).How to cite this article: Jiang, S. et al. One-Minute Room-Temperature Transfer-Free Production of Mono- and Few-Layer Polycrystalline Graphene on Various Substrates. Sci. Rep. 6, 19313; doi: 10.1038/srep19313 (2016).


In most applications based on chemical vapor deposition (CVD) graphene, the transfer from the growth to the target substrate is a critical step for the final device performance. Manual procedures are time consuming and depend on handling skills, whereas existing automatic roll-to-roll methods work well for flexible substrates but tend to induce mechanical damage in rigid ones. A new system that automatically transfers CVD graphene to an arbitrary target substrate has been developed. The process is based on the all-fluidic manipulation of the graphene to avoid mechanical damage, strain and contamination, and on the combination of capillary action and electrostatic repulsion between the graphene and its container to ensure a centered sample on top of the target substrate. The improved carrier mobility and yield of the automatically transferred graphene, as compared to that manually transferred, is demonstrated by the optical and electrical characterization of field-effect transistors fabricated on both materials. In particular, 70% higher mobility values, with a 30% decrease in the unintentional doping and a 10% strain reduction are achieved. The system has been developed for lab-scale transfer and proved to be scalable for industrial applications. Graphene has been shown to be an excellent material for opticalA manual method for graphene transfer is widely used578911121315161819202122252/Si wafers they tend to cause undesired mechanical defects on graphene films, which considerably degrade their electrical propertiesDespite of these drawbacks, the only existing automatic methods are based on roll-to-roll transfer processes27In this work we demonstrate a new system that automatically transfers the graphene layer to an arbitrary target substrate, avoiding the need of an operator and the waiting times of a typical manual transfer process. Furthermore, we demonstrate the improved carrier mobility and yield of the automatically transferred graphene, as compared to that manually transferred, as shown by the optical and electrical characterization of graphene field-effect transistors (GFETs) fabricated on both kind of materials. The system reported has been developed for lab-scale transfer, but it is fully scalable and, thus, suitable for industrial applications.The automatic transfer system is described schematically in The PTFE holding structure has been specifically designed to assist the automatic process . The choThe control electronics consist of an Arduino UNO microcontroller that is used for connecting, timing and reading the other system modules. A serial connection to a PC is used for programming and logging the process.Regarding the fluidics, two peristaltic pumps are used for introducing and removing liquid from the etch beaker. Chemical-resistant tubing connect the three containers of the liquid system: the etch beaker, and the DIW and the residues tanks. For the liquid flow, three states are available: idle, liquid introduction and liquid removal. By means of two check valves, the liquid can only flow from the DIW tank to the etch beaker and from the etch beaker to the residues tank, corresponding with the liquid introduction and liquid removal states in the peristaltic pumps system, respectively. The on/off pump conditions are controlled by means of relay switches.A contactless, ultrasound-based distance sensor reads directly the liquid level inside the etch beaker, providing the feedback signal for controlling the fluidics and determining the filling state. This sensor does not disturb the liquid surface, and is reliable even when the liquid composition is changing, as opposed to infrared sensors. The distance sensor is mounted on a micropositioner that allows fine tuning the initial distance before running the automatic process. Minimum and maximum liquid levels are defined in order to keep the graphene constantly floating in the liquid inside the container tube without touching the target substrate underneath till the very last step of the transfer process. This is a key characteristic of the automatic transfer system, as compared to the manual transfer methods, where the sample is changed abruptly to different liquid solutions using an intermediate holding substrate. Thus, the all-fluidic manipulation prevents the graphene from any strain, damage, or contamination induced by the intermediate holding substrate.The heating plate along with the temperature sensor form the temperature control unit. A proportional-integral-derivative controller is used for setting the temperature, being optimized for the working temperature range of the system (RT - 60 °C).Finally, a fan positioned on top of the container tubes is activated during the last step of the transfer process to help drying the samples.μm thickness), has been used as protective polymer. Finally, the distance sensor on top of the beaker is checked and readjusted if needed, and the tubing end is introduced at the bottom of the beaker. After this point, the system operation is fully automated with no need of operator intervention.Before starting the automatic system operation, the target substrate is loaded onto the substrate tray. For some cases, such as chemically-reactive target substrate, the substrate tray can be loaded onto the system just before the end of the process. This way, the target substrate will only contact pure DIW. For flexible substrates, such as thin PET films, a rigid holder should be used to fix the substrate to the substrate tray. For preparing the transfer process, the whole PTFE structure is introduced inside the etch beaker, with the alignment base and container tubes in place as shown in 2 membranes on 2 × 2 cm2 substrates, 400 ml of DIW are needed for the rinse, though a system design optimization could reduce this amount.In After the dilution loop, the critical part of the transfer process starts, filling the etch beaker with DIW up to the maximum liquid level , and theOnce the automatic transfer process ends, the target substrate is unloaded from the system. In In addition to the technological advantages inherent to an automated process , an automatic transfer process is expected to provide better quality graphene in terms of cleanliness (i.e. lower amount of etchant residues) and structural integrity, since the manipulation of the graphene is done in a smoother way with no intermediate holding substrate involved. The usage of an intermediate substrate in the manual transfer may cause undesired effects, as a quick capture movement is needed to perform several steps. For example, the membrane is forced an unwanted tensile strain when raised from the liquid, as the membrane is partially floating while the liquid is perturbed. Other undesired effect may be wrinkle formation around etchant residues, that may promote the adhesion of trapped ions on the graphene surface. An explanatory schematic of both mechanisms can be found in et al.μm-thick Cu foil. The chosen target substrates are 2 × 2 cm2 pieces diced from a 300 nm-thick SiO2/Si In order to demonstrate the improvement of the properties in automatically-transferred graphene, the performance of GFETs fabricated on manually and automatically transferred samples was compared. Thus, two groups of samples from the same graphene material were processed with the same conditions (see Methods), except for the graphene transfer method: the first group was transferred manually following a method derived from Sun ack-gate  inset.μ)   and the μ)  . The lat2V−1s−1). As discussed above, the gradual dilution procedure used in the automatic transfer process is likely to remove more efficiently the etchant from the graphene surface in contact with the liquid, thus reducing the unintentional doping concentration. Additionally, the all-fluidic manipulation of the graphene membrane in the automatic transfer process avoids the mechanical stress induced during the successive DIW rinse steps and the final transfer step to the target substrate of the manual method. Nonetheless, for both types of samples, the standard deviation in the mobility is similar, indicating that the dispersion may be related with the intrinsic properties of the commercial CVD-graphene used in all cases.In the case of the mobility, a clear improvement is observed for the automatically transferred samples, with a 70% increase in the mobility mean value as compared to the manually transferred samples. This is consistent with the decrease of 30% in the unintended doping for the automatically transferred samples, indicating less adsorbed impurities than in the manual method and, thus, less scattering centers reducing the mobility of the carriers in the graphene film. These results confirm that the automatic method developed degrades less the electrical properties of the material. The values reported for the manual transfer are in good agreement with literature values for the same target substrate and graphene source2V−1s−1) to eight-fold for the most demanding threshold value (2000 cm2V−1s−1). A similar behavior is found for the unintentional doping level, with a seven-fold increase in the yield for the automatically transferred devices compared with the manually transferred ones for doping concentrations as low as 1012 cm−2.It is also important to point out that the automatic transfer method provides a much larger yield. The yields of the manual and automatic transfer processes, expressed as the fraction of devices with higher mobility or lower doping values than certain thresholds, are shown in et al.Raman spectroscopy mapping has been performed in the channel area of several GFETs fabricated on both automatically and manually transferred graphene samples in order to evaluate the amount of strain and doping present in each kind of samples and correlate them with the results obtained from the electrical characterization of the devices. The analysis is based on the correlation of the frequencies of the Raman modes G , the automatic system also provides higher quality graphene. GFETs fabricated on the automatically transferred graphene present higher mobility values, lower unintentional doping and strain, and better yields as compared to those fabricated on manually transferred material. The system, initially developed as a lab-scale tool, is fully scalable for industrial applications, allowing the large-scale transfer of graphene films with superior quality to arbitrary substrates.2O2:H2SO4 1:3 vol.) during 5 minutes and rinsed afterwards thoroughly in DIW. N2 drying is performed after each DIW rinsing step. This ensures the cleanliness of the PTFE pieces and reduces their hydrophobicity for the following steps. Next, the container tubes are immersed in an aqueous solution of polystyrene sodium sulfonate (PSS) (2% in mass) for 30 seconds, rinsed in DIW, and dried with N2 afterwards. After this, another 30-second immersion in an aqueous solution of polydiallyldimethylammonium chloride (PDDA) (2% in mass), DIW rinse and N2 drying are performed. A last PSS treatment as the previous one is performed. Therefore, the final coating is composed of a layered PSS/PDDA/PSS structure.The PTFE tubes enclosing the graphene membrane during the automatic transfer process (container tubes) were surface-treated with SAMsμm-thick Cu foilhas been used as starting material for GFET fabrication. Oxygen plasma has been used for insulatingthe transistors and Ti/Au (10/200 nm) contacts were deposited by e-beam evaporation. Deviceswith gate lengths between 10 and 20 μm and widths ranging from 100 to500 μm have been fabricated. The Si n++ doped substrate, coated with 300 nm of thermally-grown SiO2, has acted as the back-gate. For the characterization, the samples were introduced inside a Janis-CCR10 probe station, which was used for degassing the last residues in graphene at 500 K for 3 hours under vacuum conditions (10−5 mbar). After letting the probe station cool down and without breaking vacuum, the current-voltage characteristics for a large number of devices in each sample were measured at room temperature. Back-gate voltage values between −40 and 65 V and a drain-source voltage of 0.2 V were used.Commercially-available monolayer CVD graphene grown on 25 μm2 in size, scanned with steps of 0.33 μm.A WITec Alpha 300AR Raman confocal microscope has been used for the Raman spectroscopy mapping of the channel area of the GFETs. Raman spectra were obtained in backscattering geometry using a ×50 objective lens  in ambient conditions. A 532 nm wavelength laser set to a power of 3 mW was used as excitation source. Typical mapped areas were 110 × 8 How to cite this article: Boscá, A. et al. Automatic graphene transfer system for improved material quality and efficiency. Sci. Rep.6, 21676; doi: 10.1038/srep21676 (2016).


Since the expression of let-7 is modulated by LINE-1 activity, we discuss possible mechanisms for this effect and how the silencing of LINE-1 activation could provide new therapeutic options for cancer treatment. Based on the deep sequencing of small RNAs in parallel with gene expression profiling in breast cancer cells, we have identified potential pathways linking L1 activity to let-7 processing and maturation and ultimately to the control of stemness in human cancer cells.Long interspersed nuclear element-1 (LINE-1 or L1) retrotransposons are insertional mutagens capable of altering the genomic landscape in many ways. Activation of the normally silent LINE-1 retrotransposon is associated with a high level of cancer-associated DNA damage and genomic instability. Studies of LINE-1 have so far focused mainly on changes in gene expression, and our knowledge of its impact on functional non-coding RNAs is in its infancy. However, current evidence suggests that a significant number of human miRNAs originate from retrotransposon sequences. Furthermore, LINE-1 is generally not expressed in normal tissues while its expression is widespread in epithelial cancers. Based on our recent studies, we demonstrate a functional link between aberrant LINE-1 expression and deregulation of  L1 is an insertional mutagen capable of copying itself and reinserting into the genome at multiple sites and is thereby capable of wreaking mutational havoc on the genome. The activation of L1 retrotransposons and ensuing L1 retrotransposition is also associated with a high frequency of DNA breaks and genomic instability  and seve mapping .c-MET, typically via alternative promoters, has been recognized (A recent survey of whole genome sequences from a variety of tumors included in the Cancer Genome Atlas (TCGA) project also identified a number of L1-mediated insertional mutations in colon, prostatic, colorectal, and ovarian cancers, suggesting that L1-induced mutations are common in cancer cells and tissues . Despitecognized , little cognized . StrikinSLC7A2, leads to a defect in the expression of the lncRNA and results in a lethal encephalopathy phenotype , which binds to polycomb group proteins and interacts with multiple target gene promoters during the process of atherosclerosis . In particular, let-7a miRNA was strongly upregulated from 149,428 normalized mapped reads to 1,855,633 reads in L1 silenced cells, accounting for 40% of the increase in the total normalized read counts in the L1-silenced cells compared to cancer cells in which L1 remained active. This massive increase in let-7a expression is intriguingly similar to the differential expression of let-7a seen in normal cells and a variety of cancer cells in which the expression of let-7 is repressed , which binds to corresponding sequences located in the 3′ UTRs of genes. Let-7a is also known to target many oncogenes including c-Myc, HMGA2, and Lin28, and its expression is a hallmark of cell differentiation. Notably, the loss of let-7a expression is often considered to have prognostic value since it indicates poor survival in many cancers. Studies performed in lung and renal cell carcinoma reveal that the overexpression of let-7a inhibits in vitro cancer cell proliferation and in vivo tumor regeneration by reducing the expression of c-Myc and c-Myc targeted genes  and negative factors . The p68/p72 RNA helicases, as components of the Drosha microprocessor complex, stimulate the processing of pri-let-7 miRNAs into mature RNAs by Dicer-mediated processing. The mature let-7a also binds to a complementary region in the pri-let-7 miRNA, recruiting Argonaute and promoting its own downregulation . In another study, inhibition of L1 activity by antiretroviral drugs was shown to reduce c-Myc expression in cancer cells , which is a component of Drosha/Dicer complexes and is known to positively regulate processing of miRNAs . Strikingly, except for pre-let-7i, all the members of the let-7 family interact with hnRNPA1. Thus, there is evidence of a relationship, at least in the case of let-7a miRNAs, between the L1 activity and miRNA expression.There is little or no direct evidence for a reciprocal relationship between the silencing of L1 and 7 miRNAs , it is c7 miRNAs . Regardlan cells . Severalan cells . Importalet-7 biogenesis. Intriguingly, our gene expression microarray profiling of L1-silenced cells showed significantly upregulated expression of the DEAH box-containing DHX9 protein, which shares high sequence similarity to the Drosophila maleless protein (MLE), a protein that regulates dosage compensation (let-7a miRNAs by recruiting a DHX9-like RNA helicase to promote its own translation (let-7a miRNAs. However, further research is needed to evaluate the precise function of L1 in the activation of the let-7 miRNAs. Given that let-7 is often viewed as a tumor suppressor miRNA, a strategy in which L1 activity is selectively inhibited pharmacologically could provide new therapeutic options for human cancer treatment.An alternative but not mutually exclusive possibility is that L1 silencing may activate miRNA-inducing proteins such as transcription factors and RNA helicases that activate ensation . DHX9 isensation  as an RIensation . Strikinnslation . Togethelet-7a. As we propose above, there is a clear link between let-7a expression and the silencing of L1 elements. Questions remain, however, as to how L1 elements, either directly or in combination with other host proteins contribute to the loss of let-7 expression in the various types of cancer. Further studies are required to thoroughly test the mechanisms proposed above by which L1 might affect miRNA expression. Regardless of the answers to these questions, the available data suggest that silencing of L1 expression holds great therapeutic potential for the treatment of various epithelial cancers.In summary, this study has explored the relationship between the expression of L1 elements and cancer onset and progression. In this study we have shown, first, that L1 activity is widespread in epithelial cancers. Second, the expression of non-coding RNAs including miRNAs and lncRNAs is closely associated with L1 activity. Third, we have demonstrated the interplay between the aberrant expression of L1 elements and miRNAs, and in particular, the tumor suppressor miRNA The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The effect of breast milk fatty acid (FA) composition, particularly levels of docosahexaenoic acid (DHA), on infant health outcomes is unclear. Part of the reason for this is difficulties in collecting, storing and shipping milk samples to the laboratory. Here we report the validation of a dried milk spot (DMS) system to measure FA composition to help overcome these obstacles.trans FA (iTFA). Experiments were carried out using pooled milk samples from US (n = 5) and Malawian women (n = 50). Experiments compared liquid vs. DMS samples (n = 55), assessed stability of FA composition under different storage conditions (n = 5), and compared the results from two different labs using the same methods (n = 5).Milk FA were measured by gas chromatography and reported as percent of total FA; the FA of primary interest in this study were DHA and industrially produced 2 = 0.99 and 0.99, respectively, P < 0.0001). The % DHA in DMS samples was stable for up to four weeks at room temperature and up to three years at -80 °C; only slight deviations from the acceptable range of variability (±15 %) occurred in the 4 °C and -20 °C conditions for % DHA. The % iTFA was stable under all conditions. All % DHA and % iTFA were within 15 % of the referent when analyzed in two laboratories.Both % DHA and % iTFA levels in liquid and DMS samples were strongly correlated  contains supplementary material, which is available to authorized users. After cooling, 40 parts of both hexane and distilled water were added. After briefly vortexing the samples were spun to separate layers, and an aliquot of the hexane (upper) layer which contained the FA methyl esters was taken for analysis by gas chromatography  as described previously [Fifty-five samples of milk from Malawian and US mothers were used to compare the FA composition of liquid vs. DMS. To make DMS samples, 1iquid milk samples were thawed and one drop of milk was placed on the collection cards. Then the DMS samples were stored at room temperature in the dark for one week before analysis . The liquid samples analyzed immediately after thawing.The five pooled milk samples from US mothers were spotted onto pretreated cards. Several DMS cards from each pool were stored in the dark in reclosable plastic bags under each of the following conditions: room temperature (23 °C), refrigeration (4 °C), standard freezer (-20 °C), and research freezer (-80 °C). At Days 4, 7, 14, 21, and 28, DMS from the first three storage temperatures were analyzed for FA composition; the Day 0 sample was analyzed immediately after spotting and served as a reference. Additionally, DMS stored at -20 °C and -80 °C were tested at months 3, 6, 9, and 12, and then every 6 months for up to 3 years.Pooled milk samples from five US mothers were placed on DMS cards and sent by express mail at ambient temperature to an affiliated lab in Seoul, South Korea (OmegaQuant Asia). Identical DMS samples were saved at OmegaQuant Analytics in Sioux Falls, SD. Sample analysis was coordinated to be done on the same day (about 1 week after shipping). Identical methods were used in both laboratories.t plus C18:2 t). If necessary, the FA were log-transformed to meet normality requirements. Spearman correlations, linear regression, and paired t-tests were used to compare the liquid and DMS samples. Correlations between liquid and dry milk samples were calculated across the full range of DHA values, and for only those samples with DHA < 1.0 %. The latter is the range in which the vast majority of milk DHA levels lies worldwide [All statistics and graphs were analyzed and created with MiniTab  and GraphPad Prism 6 . The primary FA of interest were DHA C22:6n-3) and iTFA . The linear regression equation to estimate the liquid milk % DHA using DMS data was: Liquid % DHA = 0.8974 (DMS % DHA) – 0.0015 . For the < 1 % DHA subset, the regression equation was: Liquid % DHA = 0.9116 (DMS % DHA) – 0.0054 .The % DHA of the liquid and DMS samples were highly correlated for both the whole set . The regression equation to estimate liquid % iTFA from DMS was: Liquid % iTFA = 0.9605 (DMS % iTFA) - 0.0146 . There was a greater than 15 % difference between the liquid and DMS samples for six FA  condition for up to 4 weeks or in the -80 °C freezer condition for up to 3 years  have been found to be beneficial for neurodevelopment and vision in infants and young children in some studies, but the evidence is not conclusive , 2, 18. A limitation of this validation study was the use of DMS samples that had been frozen as liquid milk, thawed then spotted onto the filter paper rather than spotted fresh. Due to the timing of the initiation of our collaboration with the research team, it was not possible to do the analyses on fresh samples. However, FA in liquid milk samples stored at -80C are stable and simulating the DMS using thawed milk and storing for 1 week at room temperature still demonstrates the value of DMS compared to traditional collection and storage methods.Difficulties in collecting, storing and transporting milk samples, particularly in field research, have limited advancements in this area. The method described here had the potential to overcome some of these challenges. One limitation of the DMS method is that (at present), the concentration of FA in milk  cannot be measured, only the percent composition. However, few researchers in this field would consider this a limitation since the vast majority of milk FA researchers have used the percent composition approach. Its appeal lies in the robustness of the analytical method, the long tradition of use, and the ability to compare results between studies. In addition, since milk percent FA composition is relatively stable during a feed and throughout the day , 22, samblood spot samples have been used for the determination of blood FA composition for many years [Logistic challenges in collection, storage and transport of samples have impeded studies where simply measuring milk FA composition is the goal. The ability to collect samples as DMS instead of liquid milk and to store and ship at ambient temperature provides a cost-effective, practical alternative without compromising the quality of the FA data. In a parallel setting, dried ny years , 10 and ny years , particuny years , 27 and ny years . The abiny years . The abiThe datasets supporting the conclusions of this article are included in the Additional file


The graphene films with low sheet resistance were grown by chemical vapor deposition. The BMN thin films were fabricated on graphene by using laser molecular beam epitaxy technology. Compared to BMN films grown on Au, the samples on graphene substrates show better quality in terms of crystallinity, surface morphology, leakage current, and loss tangent. By transferring another graphene layer, we fabricated flexible and transparent capacitors with the structure of graphene-BMN-graphene. The capacitors show a large dielectric constant of 113 with high dielectric tunability of ~40.7 % at a bias field of 1.0 MV/cm. Also, the capacitor can work stably in the high bending condition with curvature radii as low as 10 mm. This flexible film capacitor has a high optical transparency of ~90 % in the visible light region, demonstrating their potential application for a wide range of flexible electronic devices.We report a kind of electric field tunable transparent and flexible capacitor with the structure of graphene-BiThe online version of this article (doi:10.1186/s11671-015-0974-4) contains supplementary material, which is available to authorized users. Th. Th17]. graphene , 21.Fig −1, respectively [2g mode, and the 2D band is the result of a second-order process involving two phonons with opposite momentum [I2D/IG is larger than 2.0 and the full width at half maximum of 2D peak is ~30 cm−1, which can be interpreted as the structure of monolayer graphene [−1 corresponds to the breathing mode of sp2 hexagonal carbon but only gets activated by a defect with the help of a double resonance in the inter-valley scattering [IG/ID in an area of 50 × 50 μm2  of graphene on BMN film  decreases and the secondary phase MgNb2O6 (JCPDS card number 33–0857) is detected [2O6 can be ascribed to the volatilization of Bi element at high temperature. The lattice constant of the BMN films calculated from the XRD patterns is about 10.529 Å, which is similar to the value of BMN thin films on Pt-coated sapphire substrates [Figure detected . The emebstrates . Figure bstrates .Fig 4ComI{1100}/I{2110} > 1.Figure Surface roughness of the BMN films was evaluated by AFM. Figure As a kind of electrode materials, the electrical properties of graphene are an important parameter in device fabrication. The spatial distributions of sheet resistances tested on a 30 × 30 mm graphene on top and bottom of the BMN film are shown in Fig. ε is calculated from the capacitance C:Figure d is the BMN film thickness, ε0 is the dielectric constant in vacuum, and A is the capacitor area. The maximum dielectric constant reaches about 113 for the sample grown at 750 °C. The tunability of the thin films is defined as [where fined as –36:2\docε(0) and ε(v) are the dielectric constant at zero and a certain bias field, respectively. For the films grown at 550 °C, the tunability of the dielectric constant is very low of ~13.5 % at a bias field of 1.0 MV/cm, which is consistent with their relative poor crystallized phase. The tunability of the film increases with growing temperature from 550 to 750 °C, possibly due to the enhancing crystallization of the films. For the films grown at 750 °C, the maximum tenability of ~40.7 % is achieved at a bias field of 1.0 MV/cm. Compared to the BMN thin film grown at 750 °C, the sample grown at 800 °C shows a decrease of tunability, which can be ascribed to the appearance of additional phase of MgNb2O6 as illustrated in XRD patterns in Fig. 2O6 phase has a lower ε of ~19.9 and may also disorders the cubic pyrochlore structure of BMN, reducing the polarization of BMN [2O6 as shown in Fig. −5 A/cm2 at a bias voltage of 7.0 V. In contrast, the sample grown on graphene shows a low leakage current density of ~4.0 × 10−6 A/cm2 at a bias voltage of 7.0 V. The difference of the leakage current is thought to be associated with both surface roughness and crystallinity of the BMN films. For the film grown at Au, its surface has a relatively high roughness of 6.38 nm. The local electric field will vary from place to place due to the fluctuation of the film surface. At the valley, the electric field is larger than that at the peak, which increases the leakage current density of film [where n of BMN . The los of film . Moreove of film , 44. TheWe fabricated a kind of electric field tunable transparent and flexible capacitor by using graphene as electrodes. The graphene film was grown by CVD method, and the BMN thin films were fabricated on graphene by using LMBE technology. The comparison of BMN films grown on graphene with Au substrates shows that the graphene can obviously improve BMN film quality in terms of crystallinity, surface morphology, leakage current, and loss tangent. By using transfer method, we fabricated flexible and transparent capacitors with the structure of graphene-BMN-graphene. The capacitors show the largest dielectric constant of 113 and the largest dielectric tunability of ~40.7 % at 1.0 MV/cm and can work stably in the high bending condition with curvature radii as low as 10 mm. This film capacitor has a high optical transparency of ~90 % in the visible light region, making tunable capacitor highly promising for integration into flexible optoelectronic devices.


Purpose. To determine the feasibility of using 25-gauge microincision vitrectomy surgery (25GMIVS) to treat vitreoretinal disease in glaucomatous eyes which have previously undergone trabeculectomy (TLE). Methods. A consecutive, interventional case series. We performed 25GMIVS in 15 glaucomatous eyes that had undergone TLE. Follow-up period was 11.5 months. Results. 25GMIVS was successfully used and led to improvement in visual acuity (P < 0.01). We performed 25GMIVS for proliferative diabetic retinopathy with neovascular glaucoma in 53% of eyes (8 of 15). Although 3 eyes needed further TLE following 25GMIVS, final IOP was below 21 mmHg in all eyes except one eye (93%) and was comparable to pre-25GMIVS IOP (P = 0.20) without an increase in the number of glaucoma medications (P = 0.14). Conclusions. 25GMIVS is a feasible treatment for vitreoretinal disease in eyes with preexisting TLE, effective in both significantly improving BCVA and preserving the filtering bleb, while not excluding further glaucoma surgery. Trabeculectomy (TLE) is a procedure most often performed when drug-based therapies for glaucoma have been ineffective. It can effectively reduce intraocular pressure (IOP) over the long term –3, but cTwenty-five-gauge microincision vitrectomy surgery 25GMIVS) was first reported in 2002, and this procedure is now commonly used worldwide GMIVS was. One of Thus, the purpose of this study was to determine the feasibility of using 25GMIVS to treat vitreoretinal disease in glaucomatous eyes that have undergone TLE.This was a retrospective, consecutive, interventional case series performed at a single center. Fifteen consecutive post-TLE eyes of 15 patients with retinal diseases who underwent 25GMIVS were studied. The inclusion criterion was any retinal vitreous disease causing visual dysfunction in eyes that had previously undergone TLE, . The exclusion criteria were prior scleral buckling, prior trauma, and a follow-up period of less than 3 months. The preoperative demographics and postoperative courses of the patients are shown in All surgeries were performed under retrobulbar anesthesia using the oblique sclerotomy technique and were performed using the Accurus Vitrectomy System . First, an infusion cannula was inserted through the inferotemporal sclera followed by the insertion of two cannulas through superotemporal and superonasal sites. The insertion point of the cannulas was shifted as necessary to avoid disturbing the conjunctiva adjacent to the filtering bleb. Next, a 2.4 mm superotemporal corneal incision was made, followed by phacoemulsification, aspiration (PEA), and intraocular lens (IOL) implantation before the vitrectomy, if the eye had a cataract. After resecting the vitreal core, 4 mg of triamcinolone acetonide  was injected into the vitreous cavity to determine if a posterior vitreous detachment (PVD) was present. If a PVD was not present, we created one with a 25-gauge cutter. After shaving the peripheral gel, the proliferative membrane was removed, and fluid air exchange and endophotocoagulation were performed if needed. The exact surgical procedures varied according to the type of vitreoretinal disease. Additional TLE was also performed under retrobulbar anesthesia, with a fornix-based conjunctival flap. A half-thickness 4.0 by 4.0 mm rectangular scleral flap was made in the superior area. Mitomycin C (MMC) was used with a concentration of 0.04% and an exposure time of 5 minutes. The area was irrigated thoroughly with 200 mL of balanced salt solution. Trabeculectomy was then performed, followed by peripheral iridectomy. The scleral flap and conjunctiva were closed with a 10-0 nylon suture. Postoperatively, antibiotics and corticosteroids were injected subconjunctivally.We evaluated best-corrected visual acuity (BCVA), IOP, number of glaucoma medications, intraoperative subconjunctival hemorrhage, intraoperative suturing at the sclerotomy site, and additional TLE (after 25GMIVS). BCVA was measured using the Landolt C visual acuity chart, and the decimal BCVA was converted to logarithm of the minimal angle of resolution (LogMAR) units for statistical analysis. Success of the 25GMIVS procedure was defined as improvement or maintenance of BCVA and maintenance of IOP ≤21 mmHg with the use of topical glaucoma medication, with no need for additional TLE. The procedure was recorded as a failure if there was a decrease in BCVA, additional TLE was required, or IOP could not be maintained ≤21 mmHg with the use of topical glaucoma medication. t-test. For the statistical analysis, “count fingers” visual acuity was set as 2.0 logMAR units, and “hand motion” acuity was set as 3.0 logMAR units. The significance of the difference in IOP before TLE, after TLE, and after 25GMIVS was determined by the Friedman test, and the significance of the difference between the IOP after TLE and after 25GMIVS was determined by the Scheffe's test. The significance of the difference in the pre-25GMIVS number of glaucoma medications and the final number was also determined by the two tailed paired t-test. A P value of less than 0.05 was considered to be statistically significant.The data are presented as the mean ± standard deviation. The significance of the difference between the pre-25GMIVS BCVA and final BCVA in logMAR units was determined by the single tailed pairedA summary of the patients' characteristics and pre-25GMIVS course is shown in P = 0.01). Pre-TLE IOP, pre-25GMIVS IOP, and final IOP were 36.0, 11.9, and 15.7 mmHg, respectively. There were significant IOP differences pre-TLE, pre-25GMIVS, and post-25GMIVS (P < 0.001), but no significant difference between the pre-25GMIVS IOP and final IOP (P = 0.20). There was no difference in the pre-25GMIVS and final number of glaucoma medications (P = 0.14). Subconjunctival hemorrhage occurred in 5 eyes (33%); however, in 3 of these eyes, there was no hemorrhage invasion into the filtering bleb. Four eyes (27%) had intraocular pressure >20.0 mmHg after 25GMIVS, and 3 of these eyes needed additional TLE. It should be mentioned that this additional TLE was a technically simple procedure, because 25GMIVS had been performed without any sutures. Vitreoretinal diseases in all 15 eyes with preexisting TLE were successfully treated with 25GMIVS. We achieved success with 25GMIVS in 10 cases (67%) and did not observe surgical complications, such as bacterial endophthalmitis, associated with either TLE or 25GMIVS in any of the cases. The mean follow-up period was 11.5 ± 7.7 months with a range of 6 to 34 months.A summary of the patients' characteristics and post-25GMIVS course is shown in We set out to evaluate the feasibility of using 25GMIVS to treat vitreoretinal disease in glaucomatous eyes that had undergone TLE. The most common vitreoretinal disease in eyes with preexisting TLE we treated with this technique was PDR complicated by NVG . In spite of the relatively high incidence of such a severe disease, mean BCVA improved significantly after 25GMIVS. Additionally, although 3 eyes needed further TLE following our 25GMIVS procedure, the final measurement of IOP was statistically comparable to IOP before 25GMIVS, without an increase in the number of glaucoma medications. Furthermore, because of our use of sutureless 25GMIVS, the additional TLE procedure itself, following 25GMIVS, was not more difficult than a standard TLE procedure.Our results confirm existing data that, in about one-third of cases, eyes will develop elevated pressure if they undergo vitrectomy after TLE . About 3We speculate that subconjunctival hemorrhage during 25GMIVS affects the preexisting filtering bleb. Many earlier reports have demonstrated the advantages and disadvantages of using autologous blood injection to treat overfiltering or leaking blebs after glaucoma surgery –33. ThusThere were limitations to our study, including the retrospective nature of the analysis, a short follow-up period, and a small number of patients. We did not discuss filtering bleb function in detail because our study included eyes with blebs whose function before 25GMIVS was doubtful (these eyes continued to need glaucoma medication after TLE). Furthermore, we did not compare 25GMIVS and 20GPPV. A comparative, prospective study in post-TLE eyes would provide valuable insights into the relative value of these techniques but is impossible due to ethical considerations, making an experimental analysis using an animal model perhaps the most useful approach for such a future study. Nevertheless, as post-TLE eyes that require glaucoma medication for IOP control before vitrectomy are commonly observed clinically and indeed comprised about 50% of the cases in our study, we believe that this is a valuable study of a useful treatment for post-TLE eyes with various retinal conditions. Further investigation is needed to evaluate postoperative visual quality and complications in the late postoperative period before a final determination can be made of the efficacy of this procedure.In conclusion, 25GMIVS is technique that can feasibly be used to treat vitreoretinal disease in glaucomatous eyes that have undergone TLE. Regardless of a high incidence of PDR with NVG in our case series, we were able to achieve good final results for BCVA and IOP with 25GMIVS, without increasing the number of glaucoma medications. Though there were a few cases that needed additional TLE following 25GMIVS, the additional TLE procedure was not more technically difficult than usual, because of the good condition of the conjunctiva after sutureless 25GMIVS. Our results showed that 25GMIVS was effective in preserving the filtering bleb and the other quadrant conjunctiva in eyes with glaucoma and did not exclude further surgical intervention for this disease.


Graphene photo-detectors functionalized by colloidal quantum dots (cQDs) have been demonstrated to show effective photo-detection. Although the transfer of charge carriers or energy from the cQDs to graphene is not sufficiently understood, it is clear that the mechanism and efficiency of the transfer depends on the morphology of the interface between cQDs and graphene, which is determined by the shell of the cQDs in combination with its ligands. Here, we present a study of a graphene field-effect transistor (FET), which is functionalized by long-ligand CdSe/ZnS core/shell cQDs. Time-resolved photo-luminescence from the cQDs as a function of the applied gate voltage has been investigated in order to probe transfer dynamics in this system. Thereby, a clear modification of the photo-luminescence lifetime has been observed, indicating a change of the decay channels. Furthermore, we provide responsivities under a Förster-like energy transfer model as a function of the gate voltage in support of our findings. The model shows that by applying a back-gate voltage to the photo-detector, the absorption can be tuned with respect to the photo-luminescence of the cQDs. This leads to a tunable energy transfer rate across the interface of the photo-detector, which offers an opportunity to optimize the photo-detection. In recent years, graphene has been widely used for the development of new electro-optical devices such as transparent electrodes45789121314151618et al.In general, the transfer consists of two parts: the charge transfer/Dexter transfer21222425Herein, we first built up a graphene field-effect transistor (FET) via a simple laser ablation method, which avoids a chemical photo-lithography process. We measured the time-resolved photo-luminescence (TRPL) on a graphene FET functionalized with CdSe/ZnS QDs at different back-gate voltages. A Förster transfer model is elucidated from the back-gate dependence of the PL lifetime. The optimization of the back-gate voltage for an efficient energy transfer is discussed together with a consideration of the device’s responsivity.τ1 = 30 ± 1 ns and a slow decay with τ2 = 7.0 ± 0.5 μs. A graphene FET was fabricated using laser ablation and electrical contacts (Ti/Au:20 nm/200 nm) were deposited using metal evaporation in combination with a laser-cut shadow mask. The cQDs employed exhibit a PL peak at 580 nm and the first exciton absorbance peak at 560 nm. The characterization of absorbance as well as the photo-luminescence of these cQDs in solution are provided in the To obtain insight into the transfer dynamics, three independent measurements with different but similar transistors were performed for the statistics, which demonstrate qualitative accordance. Indeed, those devices, which are based on the same design and are the result of the same fabrication technique, exhibited a similar structure as well as cQD coverage within fabrication tolerances cf. . The recP. We can observe a shift of the response curve at functionalization as well as at different light intensities, as shown in et al.Iph − Idark)/(P), with Iph representing the current at given illumination (P), and Idark the FET current in the dark, respectively. Such responsivity curve is plotted in et al.Furthermore, the shift of the Fermi level depending on the optical power was investigated for one of the transistors representatively. The resistance-response curve was therefore measured at different optical powers ωFRET is therefore proportional to the integral of the photo-luminescence of the quantum dots PLQD (a measure of the number of excited cQDs) and the absorbance of graphene αGr (see Since we have been investigating a system with long ligands (oleic acid), we expect the transfer to be dominated by a Förster-like energy transfer αGr see :VBG is changed, the Fermi level EF in the graphene is being tuned and the absorbance changes accordingly. In other words, by changing the back-gate voltage, one shifts the absorbance of graphene with respect to the fixed radiative transition energy, i.e. PL line, of the cQDs. The absorbance of graphene α(ω) consists of two parts, as ω)-dependent intraband absorbance αintra(ω) and the interband absorbance αinter(ω).This means that the transfer rate peaks, when the high absorbance of graphene overlaps with the PL energy of cQDs, and decreases, when the absorbance of graphene mismatches the PL energy of QDs at a certain energy detuning. If the back-gate voltage q = −1, Eres = 5.02eV. The interband absorbance can be modelled by equation (3)EF relative to the Dirac point in the frequency-dependent optical sheet conductivity σ(ω), with (π2e2)/(ch) comprising of natural constants  and kBT the thermal energy at room temperature:To include the effect of the exciton resonance, the interband absorbance has been multiplied by the fanofunction according to ref. τs = 50 fs representing the momentum relaxation time at charge neutralityThe intraband part can be modelled by a Drude modelσExp0, –conductivity at the Dirac point, represented by 1/RExp(0V) –has been normalized to the theoretical value RExp(VBG) − RContact), which takes into account the estimated contact resistance of each device, is particularly used to estimate the uncertainty of the model values extracted for the absorbance.The measured conductance α(ω) given by λ = 2πc/ω in the range of 530 nm to 640 nm (corresponding to the cQD emission line) and is plotted in RSD paired with Fermi energies. In addition, the displayed chart in RExp(VBG) are shown in −log(I/I0) in units of πα = 0.023. Here, the relative absorbance only considering interband transisions amounts to 1, while α of The absorbance τeff consisting of two parts similar to Niebling et al.τQD,pure of the cQDs  on silicon, similar to Kim The time-resolved photoluminescence (PL) measurements were performed using a frequency-doubled Nd:YAG laser (Quantel Brilliant) at 532 nm and 10 Hz repetition rate with 1.5 μJ per Pulse. The optical signal was collected and focused onto a spectrometer (Oriel Instruments MS-257) with a blaze grating of 300/500. Using a gated intensified charge coupled device (ICCD), transients of PL were measured. For current and bias voltage control, respectively, two current meters (Keithley 617) were employed. One of them was used to apply a 50 mV source-drain bias voltage to monitor the resistance of the graphene channel, while the other device was used to set the back-gate voltage. The gold contact pads on the sample were electrically contacted by tungsten needles cf. . For theHow to cite this article: Li, R. et al. Gate Tuning of Förster Resonance Energy Transfer in a Graphene - Quantum Dot FET Photo-Detector. Sci. Rep.6, 28224; doi: 10.1038/srep28224 (2016).