Metal films deposited on graphene are known to influence its electronic properties, but little is known about graphene’s interactions with very low work function rare earth metals. Here we report on the work functions of a wide range of metals deposited on n-type epitaxial graphene (EG) as measured by Kelvin Probe Force Microscopy (KPFM). We compare the behaviors of rare earth metals  with commonly used noble metals . The rare earth films oxidize rapidly, and exhibit unique behaviors when on graphene. We find that the measured work function of the low work function group is consistently higher than predicted, unlike the noble metals, which is likely due to rapid oxidation during measurement. Some of the low work function metals interact with graphene; for example, Eu exhibits bonding anomalies along the metal-graphene perimeter. We observe no correlation between metal work function and photovoltage, implying the metal-graphene interface properties are a more determinant factor. Yb emerges as the best choice for future applications requiring a low-work function electrical contact on graphene. Yb films have the strongest photovoltage response and maintains a relatively low surface roughness, ~5 nm, despite sensitivity to oxidation. These photonic properties, when considered in combination with graphene’s high Fermi velocity, high mobility, and relativistic quantum electronic transport, suggest the opportunity to create a variety of unique photonic devices9. Among these devices, graphene optical detectors have been demonstrated with light intensity modulations of 40 GHz without degradation of the photoresponse, and transfer data as fast as 12 Gbits s−1 12. Such devices have great potential for use in the development of faster data transfer networks for optical telecommunications. Graphene optoelectronic devices operating in the terahertz gap between 0.1 and 10 THz are even more promising16, as THz technology in this range is emerging as a potential solution for a variety of problems in fields as diverse as cancer detection, atmospheric monitoring, and security screening19. Graphene’s two-dimensional lattice affords limited opportunities for lattice-electron energy loss22, thereby causing absorbed THz radiation to induce a hot-carrier effect, a useful mechanism for THz detection22. Graphene-based THz detectors currently achieve responsivities as high as 400 V W−1 and there are good indications for potential improvement23.Graphene, a single atomic layer of sp23. Metal films can dope graphene, causing junctions to form at the edge of each contact, thus generating a photoresponse when illuminated24. Scanning photocurrent measurements across metal-graphene-metal junctions reveal that the photoresponse is maximized near each metal-graphene junction, but vanishes in the center of the channel26. The photoresponse is dependent upon a combination of photovoltaic effects from the induced electric field and photothermoelectric effects from the Seebeck coefficient differences of differently doped graphene29. The mechanism is similar to the hot-carrier dominated photoresponse at graphene P-N junctions28. Moreover, the amount of doping induced by the metal is largely determined by its work function, ϕ24. This is important in detectors because using different metals at the source and drain creates an asymmetry that induces a net photoresponse, with the magnitude determined by the Δϕ of the two metals; this means that the maximum response should be obtained using contacts with the largest work function difference. Photodetectors operating in both the telecommunication and THz spectrum have already been developed using this type of architecture23. While back gating can improve performance, passive THz devices have responsivities as high as 200 V W−1 23. This asymmetric contact design enables rapid and wafer-scale fabrication of graphene devices by minimizing processing steps and reducing the need for split gating.While conventional semiconducting photodiodes utilize a P-N junction, efficient graphene devices can be fabricated with a single strip using different metals for the source and drain contacts35. Therefore, a preliminary study of the qualitative interactions between graphene and metals with a large range of ϕ is essential for various applications including photodetectors utilizing metal contacts that induce a voltaic asymmetry. There is very limited research on low work function thin films on graphene. The majority of graphene studies involving erbium and ytterbium metals use the metals as dopants in laser fibers37, while europium oxide films on graphene are used for spintronics due to EuO’s ferromagnetic capabilities40, and yttrium oxide is used as a high κ dielectric42. However, to our knowledge there are no studies in the literature that characterize these metals or their oxides for their capability to function as an electrical source/drain contact. For example, pairing a low work function contact with a noble metal should result in improved performance of graphene-based two-terminal photodetectors.Despite the usefulness of metal-graphene junctions, little published work exists that quantifies the behavior of different work function metals on graphene that can aid the optimization of device design and fabrication. While there has been extensive work on graphene-metal contacts, these studies largely pertained to achieving low contact resistance and have focused on metals with high work functionsϕ for the low work function category, with the measured ϕ consistently higher than expected. A number of metals introduce significant processing challenges and unique characteristics when deposited on graphene. Er and Pr films form micrometer-sized topographic features likely due to adhesion issues and complications from volumetric changes during rapid oxidation. Eu films exhibit unique phonon signatures when on graphene. A thorough examination of the graphene-metal interface at the Er film edge shows evidence of disorder in the graphene lattice, suggesting that sp3 bonding or oxidation of the graphene lattice may occur during metal oxidation. For Eu deposition, we also report on a redshift in the graphene Raman spectrum, possibly due to Eu-adsorption or Eu intercalation with the graphene lattice4. A preliminary analysis of photoresponse uncovers no correlation between photovoltage and surface potential, with the photovoltage values largely determined by the physical characteristics of the metal-graphene interface. Of the rare earth films studied, Yb films are the most encouraging because they exhibit the strongest photoresponse and smallest surface roughness.In this study, we deposit metals with work functions ranging between 2.5 eV and 5.8 eV on graphene grown epitaxially on SiC via Si sublimation. We find a discrepancy between the reported and measured values of 44.Figure We note here an important characteristic of KPFM scans. For the metal thicknesses used, KPFM measurements are not sensitive to sample  topography and, in the absence of chemical reactions, only depend on the material properties near the surface. This characteristic is exemplified by the Er scans. The interface where the Er pad overlaps the Au pad is not visible in KPFM Fig. . Yet, thϕR) and calculated work functions (ϕM) of the metals deposited in this study, as well as the measured SPD between the metal film and graphene (SPDM-G) is found in Table 146. The measured values and variance presented in Table ϕAu, is 5.10 eV based on referenced values of Au and the SPD between Au and graphene48. We use this value as our comparative reference to calculate the work functions for graphene and the other metals using the measured surface potential. For example, to calculate the work function of EG on a terrace using data found in Fig. q) and the value of ϕAuto find ϕG. A summary of the reported , Au(110), and Au(111) have work functions of 5.47, 5.31, 5.37 eV, respectively47. Similarly, the work function of Cu varies with orientation, ranging from 4.48–4.98 eV47. In any case, we emphasize that our KPFM results for the high work function metals are reproducible over the course of months.For the high work function metals, the discrepancy from literature values cannot be due to substrate effects since, as we discussed earlier, KPFM is sensitive to the surface properties of the metal; we also specifically tested and confirmed this characteristic using a different substrate. Moreover, the KPFM system is likely not the source of the discrepancy since we obtain reproducible results over the course of months and the calculated work function of graphene is the same as other reports that use calibrated KPFM tips5/2) peak was located at 185.87 eV indicative of Ytterbium oxide. Because of the metal oxidation, the surface potential measurements are expected to differ from the pure metals. For the case of Pr, the calculated ϕ is expected to increase with increasing oxygen exposure, due to the presence of Pr2O353, and this appears to be consistent with KPFM measurements in Fig. 2O3 having reported ϕ values of 1.8 and 2.0 eV, respectively56. And the case of EuO is further complicated because the work function is strongly dependent on orientation, e.g., the work function of EuO(111) is 7.5 eV, which is considerably higher than 1.8 eV of EuO(100)54. In general, oxidation of the deposited metal will change ϕ and the data imply that it generally increases. The experimental conditions used in this work are similar to those encountered in processing actual devices, including exposure of the devices to ambient during the device fabrication and subsequent possibility of oxidation as exhibited here.The discrepancy from literature values for the low work function metals, in addition to the purity issues noted above, is likely due to oxidation. These metals are known to oxidize rapidly when exposed to the atmosphere. Despite measuring the surface potential directly after metal deposition, the metals Eu, Y, Er, Yb, and Pr, begin oxidizing upon removal from the deposition chamber. The oxidation is optically apparent on the samples because the appearances of the deposited rare earth metal films change from reflective, to opaque, and then to semi-transparent or transparent within minutes to hours. We confirmed the oxidation by XPS measurements; for example, XPS showed that the Yb . Note that the Y work function does not change when overlapping gold, as is expected. In Fig. 2CrO3 has been reported to form during joint sputtering of Y and Cr films58. In that case, the overlapping region in Fig. 2CrO3 mixed with Y and Cr and we propose 3.93 ± 0.09 eV as the mixture’s previously unreported work function. Of the eleven metals investigated in this work, this is the only instance of a metal’s work function changing when overlapping another metal.To help guide utilization of the five rare earth metals for graphene applications, we look more closely at the film characteristics after deposition on EG. Y films were deposited after Cr causing Y to overlap Cr, and one such intersection is shown in Fig. Er and Pr deposited films on EG have similar morphology and surface potential characteristics. Deposition of both metals (100 nm) on EG results in raised hemispherical features (bubbles) Fig. . These bϕ changes over time. Moreover, as noted earlier for the Pr deposited films, the magnitude of ϕ is consistent with the formation, at least in part, of Pr2O3. Figures Since the bubble morphology evolves with exposure to the ambient atmosphere over a time span of 1–3 hours, this characteristic is likely due to oxidation of the Er and Pr films. This mechanism is supported by KPFM measurements, summarized in Table ϕPr has an unusual dependence on the underlying material; it is the only metal whose surface potential is dependent on whether or not the scan is taken with respect to Au or Graphene. From Table Pr-G is +0.10 ± 0.03 eV at t = 0 and +0.54 ± 0.03 eV at t = 60 min. However, when measured against Au the SPDPr-Au is −0.76 ± 0.02 eV at t = 0 and −0.48 ± 0.02 eV at t = 60 min. Using ϕAu = 5.10 eV, this corresponds to a ϕPr of 4.34 ± 0.02 eV and 4.62 ± 0.02 eV at t = 0 and t = 60 respectively. This is a 0.53–0.69 ± 0.06 eV difference than when measured against graphene. It is unclear why this discrepancy occurs with Pr, but one possibility might be that the Pr is charging during measurement. Pr2O3 is known to be a high-κ dielectric oxide, and the graphene-Pr interface is likely very inconsistent considering the high surface roughness and tall features59. Alternatively, the Pr film is much smoother when overlapping Au, which perhaps discourages charging, resulting in a lower measured surface potential.For the Pr deposited films, −1, respectively. The other peaks are from incompletely subtracted contributions of the SiC substrate. In the Raman maps, Fig. −1 in the unaffected graphene to 2685 ± 5 cm−1 along the perimeter. Likewise, the G peak in Fig. −1 to 1585 ± 5 cm−1. Spectroscopic shifts in these peaks are consistent with EG lattice strain and/or doping60. From Fig. 2 symmetry62. We propose that during oxidation of the Er pad the EG along the perimeter of the film is affected, reacting with the metal and/or oxide resulting in the formation of erbium carbide or forming graphene oxide. Furthermore, the Raman shifts in the G and 2D peaks are the result of strain created by the reactions at the perimeter62.To evaluate the effect of Er metal deposition on the underlying EG, including areas underneath the hemispherical features, the sample was sonicated in de-ionized water for 5 seconds. This removed the Er pads but not the Au pads, consistent with the hypothesis of poor adhesion. The exposed region was probed by Raman spectroscopy. Figure Another deposited metal that shows evidence of altering EG’s Raman signature is Eu. Figure −1, 2473 cm−1, 1990 cm−1, and 1893 cm−1 labeled α, β, γ, and Δ, respectively. Also, the spectrum is approximately ten times stronger in intensity. This suggests that the deposited Eu film results in resonant Raman scattering when 532 nm excitation is used, possibly due to electronic transitions associated with Eu oxides and/or other compounds created by reaction with the EG. Our results are comparable to a report of EuO deposition on graphene show strong EuO Raman signatures with similar peak positions when using a 535 nm laser40.We used Raman spectroscopy to characterize the EG covered by Eu. Figure 2 bonds. We propose that this is due to Eu-C bonding and possibly Eu and/or EuO intercalation. Eu and EuO films on graphene are known to intercalate under the graphene lattice, and can increase graphene conductivity, even inducing a band gap from the hybridization of EG/Eu/SiC buffer layer63.Using the 455 nm probe, we acquire a Raman spectrum at a white spot in the Eu film, shown in Fig. except the entire region under the deposited Eu is affected. For example, the 2D and G peak positions exhibit a red shift towards lower wavenumbers, see Fig. −1 in uncovered EG to 2715 ± 5 cm−1 for the deposited region. Likewise, the G peak shifts from 1595 ± 1 cm−1 in uncovered EG to 1577 ± 3 cm−1 for the deposited region. By contrast, studies of ultra-high vacuum deposition of EuO on CVD graphene result in a blue shift in the Raman spectrum40. Lastly, we find regions of substantially high D/G peak ratios in Eu covered EG, see Fig. Raman spectroscopic maps of the 2D peak position, G peak position, and D/G ratio of the graphene underneath the deposited Eu film are shown in Fig. As discussed for the case of deposited Er, as well as in the discussion in the paragraph above, the spectroscopic shifts in these peaks are consistent with damage to the graphene lattice, strain, oxidation, and intercalation.The last of the rare earth metals, Yb, was comparatively unremarkable. Upon deposition, the film was relatively smooth with a surface roughness of only 5.0 ± 0.3 nm, see Table VOC, when the metal-EG interface is illuminated as a scanned 532 nm laser is moved across the pads; this approach is similar to other reports26. Figure VOC for the difference between the reported and calculated work functions for Eu, Yb, Er, Rh, Ni, Au and Pt, and Fig. VOC as a function of surface roughness. Since the metal-graphene perimeter interface can vary from sample to sample due to various effects  epitaxial graphene (EG) was synthesized by Si sublimation, in a controlled Ar ambient, on nominally on-axis semi-insulating (0001) 6H-SiC using a commercial CVD reactor; additional details are found elsewhere−6 Torr. Unless otherwise noted, 25–30 nm of metal was deposited. We used a shadow mask to avoid photoresist contamination for each deposition and the deposition rate was 2–3 Å s−1, with exceptions for Yb and Eu. For Yb and Eu, the deposition occurred at a rate much greater than 2–3 Å s−1 even at the lowest beam power due to the high evaporation rate of the source material. Three metals  were deposited on each graphene sample in overlapping but shifted patterns.Metals of varying work functions  and Kelvin probe force microscopy (KPFM) with a Bruker Dimension Icon. Bruker SPCM-PIT tips with a lift height of 90 nm were used and scans were 20–50 μm wide to prevent scanning interference effects at the graphene-metal film interface. The first scan was taken within ten minutes after removal from the evaporation chamber. The surface roughness (RMS) was extracted from AFM scans over areas of 10 μm × 10 μm; before metal deposition the graphene films had a roughness of 1.7 ± 0.2 nm. Optical images of the surface were taken with either the camera embedded in the Bruker AFM or an Olympus BX60M optical microscope. The temperature and humidity of the KPFM lab space were approximately 72 °C and 38% respectively.The surface morphology and Photovoltage measurements were obtained by illuminating the sample with a 1 mW, 532 nm laser using a 1 μm spot size while recording the open circuit voltage measured by Be-doped Cu probe tips with a 50 μm spacing making contact with two identical deposited metal pads. A ThermoFisher DXRxi using a 9.6 mW, 532 nm or 6 mW, 455 nm confocal probe having a ~0.5 μm spot size was used to acquire the Raman spectroscopy data. X-ray Photoelectron Spectroscopy (XPS) using a Thermo Scientific K-Alpha system with a monochromatic Al source (Kα = 1486.6 eV) was used to analyze the chemical states of the rare earth metals. A low-energy electron flood gun was used for charge compensation and all core level peaks were fitted using a Shirley background subtraction.


Graphene has made significant contributions to neural tissue engineering due to its electrical conductivity, biocompatibility, mechanical strength, and high surface area. However, it demonstrates a lack of biological and chemical cues. Also, it may cause potential damage to the host body, limiting its achievement of efficient construction of neural tissues. Recently, there has been an increasing number of studies showing that combining graphene with other materials to form nano-composites can provide exceptional platforms for both stimulating neural stem cell adhesion, proliferation, differentiation and neural regeneration. This suggests that graphene nanocomposites are greatly beneficial in neural regenerative medicine. In this mini review, we will discuss the application of graphene nanocomposites in neural tissue engineering and their limitations, through their effect on neural stem cell differentiation and constructs for neural regeneration. Peripheral nerve injury (PNI) has been widely reported to be an essential cause of incapability in the clinical setting. Patients suffering from this disease encounter many challenges including pain, sensory loss, impaired movement, and cold intolerance, which have a significant adverse impact on their daily life . The mossp2 hybridization, forming a honeycomb pattern throughout the 2D plane [Recent advances in tissue engineering and regenerative medicine have paved the way for the development of many strategies in peripheral nerve repair and various functional topographical scaffolds such as gels, films, electro spun fibers, and grooves which have been successfully demonstrated to support neuronal cellular attachment and migration . Due to 2D plane . Highly 2D plane . Notably2D plane ,14. Comp2D plane . However, while pristine graphene can induce synaptogenesis and sustain neuronal growth, pure graphene sheets fail to recapitulate the intrinsic neural microenvironment in vivo due to its smoothness, chemical inertness and lack of biological cues ,19,20. IIn this mini review, we will first touch upon the structure and functions of graphene nanocomposites. The main focus will be on recent research advances in graphene-based nanocomposites for application in neural tissue engineering. Finally, we will provide a summary and perspectives for using graphene nanocomposites as the next generation of materials for neural tissue engineering.Graphene-based nanomaterials (GNs) can be subdivided according to the number of layers, sheet dimensions, surface chemical modification status, and defect density. The most widely applied ones are single-layer graphene, few-layered graphene, GO, as well as reduced graphene oxide (rGO), as shown in Inspired by their fascinating physical and chemical properties, the GNs have been widely applied to neural tissue engineering; however, some substantial problems have significantly hindered their application. For example, most of the above GNs have been demonstrated to possess an aggregation tendency, cytotoxicity and insufficient bioactivity in physiological environments because of the strong interaction among nano-sized graphenes, uncleared biocompatibility and their inherent bio-inert nature . Thus, fUtilizing graphene’s unique surface and electrical properties to mimic in vivo cues to enhance the differentiation of stem cells into neurons is an extremely attractive strategy for the treatment of neuronal injuries and diseases. Reports have shown that GN-based materials promote stem cells to differentiate into neurons, as well as improve their proliferation rate ,49,50. HIn one study, Akhavan et al. cultured neural stem cells (NSCs) on ginseng-reduced GO nanosheets to improve the material’s biocompatibility and capability for electron transfer . Using gTo investigate the effect of the physical cues of graphene composites on human neural stem cells (hNSCs), Solanki et al. functionalized laminated GO nanoparticles on charged glass to form aligned patterns, matching the extracellular matrix (ECM) protein patterns in the human body . GO was However, the aforementioned studies were only able to capture the differentiation of NSCs on a 2D plane, which is very different from the three-dimensional (3D) ECM nanostructure. The signaling between cell-microenvironment interaction and attachment of cells onto a 3D dynamic network of macromolecules is essential to maintaining stem cell homeostasis . In addi2 matrix containing TiO2 nanoparticles. After 3 weeks of differentiation, the number of cells increased up to ~26.8-fold. Notably, the nano-grids showed lowered electrical resistance due to the connection by neurite network, implying that formation of cell-to-cell electrical couplings existed in the differentiated network. However, the neural network formed by nano-grids was limited to the 2D plane. Hence, researchers have been searching for substitutes such as nanofiber scaffolds for cultivating neural cells [Other than promoting neuronal differentiation to replace damaged tissues, GNs can also directly stimulate neural regeneration as electrodes. Electrical stimulation is vital to promoting cell proliferation and mimicking in vivo neural networks as neural cells are interconnected via neurites in native tissues . For exaal cells . Electrically conductive nanofibers additionally provide cells with favorable 3D architecture and appropriate flexibility similar to neurites in the human body. The attractiveness of using graphene to fabricate nanofibers instead of traditional conductive materials such as carbon nanotubes and poly comes from graphene’s superior electrical properties and mechanical strength. While the smooth transition from graphene’s 2D sheet to 3D nanofibers may prove to be difficult, Feng et al. circumvented the problems by assembling a GO sheet onto the surface of electro-spun poly (vinyl chloride) nanofibers, allowing the surface of the nanofiber to be wrapped tightly with graphene . The fibIn conditions like glaucoma, high intraocular pressure induces lesions in the optical nerves. While reduction of pressure can halt the damage done to retinal ganglion cells, their function cannot normally be recovered. However, the construction of nanofibrous scaffold using graphene, conductive polymer polypyrrole and polylactic-co-glycolic acid (PLGA) allowed for a high surface area for cell attachment as well as high capacitance for electrical stimulation, guiding cell neurites to regenerate along aligned fiber patterns. Through electrospinning, a fibrous mat structure with diameter at 110 nm was collected. It was shown that the fibers have tunable electroactivity by varying the ratios of graphene and polypyrrole in PLGA, allowing for a flexible therapy for optical nerve-related diseases. Results also showed the importance of electrical stimulation to the anti-aging ability of retinal ganglion cells. Without electrical stimulation, the cells showed decreased size, increased roundness and number of tentacles, resulting in mass apoptosis and lowered cell viability to 40% of the original. The ganglion cells, however, remain healthy after 10 days when electrical stimulation was applied, showing the essentiality of electrical stimulation to neural constructs. Reports have showed that electrical stimulation is essential to calcium-dependent neurite outgrowth and immediate gene expression, and that regeneration rate is frequency-dependent . Hence, While graphene itself can be used as a substrate, platelets of graphene can also be infused with other materials such as polymers to exhibit specific bulk properties while retaining its conductivity and chemical cues . AlthougAdditionally, GNs were applied in neural regeneration through drug loading and delivery through the blood brain barrier, which is normally impassable for drug molecules ,64. A naNeurodegenerative and neurological diseases like Alzheimer’s disease and Parkinson’s disease threaten an ever-increasing percentage of our ageing population. Studies have shown that deep brain stimulation and recovery of sensory capabilities by electrical stimulation based on neural recordings are extremely beneficial to neural regeneration . Hence sIn one study, Kuzum et al. fabricated transparent graphene electrodes for simultaneous electrophysiology recording and neuro imaging using graphene and polyimide . The fleGraphene has been widely proved to play a vitally important role in the proliferation and differentiation of neural cells. Significant progress has been made during the past decades in the development of graphene-based materials ,55. Up tWith the increasing utilization of graphene in a variety of biomedical applications, the in vitro and in vivo biocompatibility of graphene and its derivatives and their probable toxicities must be taken into consideration. The critical parameters which result in toxicity using graphene-based materials are: (1) The size, concentration, and shape. Smaller sizes and higher dose could lead to significant toxicities, giving rise to the fragmentations of DNA and/or chromosomal aberrations in living cells. The potentially sharp edges of graphene flakes or platelets would also result in physical damage of the wall membrane of cells and even nuclei through the direct contact interaction with cells; (2) Their possible aggregation, which may bring about adverse effects  to the blood circulation or immune system ; (3) IntAdditionally, most studies only focus on the exterior cell behaviors upon graphene exposure, thus, the interior effect of intracellular processes should be more emphasized ,75. For 2 nanoparticles and near-infrared ray-assisted photodegradation to provide a noninvasive method for circumventing this limitation [The possibility of biodegradation of graphene-based materials is another challenging issue, which should be solved especially when graphene impedes the effective interaction of cells and/or exchange of ions . Severalmitation ,79. HoweOverall, although there are still various unresolved issues and challenges, GNs are promising substances to pave the way for a real breakthrough in future studies of neural regenerative medicine.


Poly(methyl methacrylate) (PMMA) is widely used for graphene transfer and device fabrication. However, it inevitably leaves a thin layer of polymer residues after acetone rinsing and leads to dramatic degradation of device performance. How to eliminate contamination and restore clean surfaces of graphene is still highly demanded. In this paper, we present a reliable and position-controllable method to remove the polymer residues on graphene films by laser exposure. Under proper laser conditions, PMMA residues can be substantially reduced without introducing defects to the underlying graphene. Furthermore, by applying this laser cleaning technique to the channel and contacts of graphene field-effect transistors (GFETs), higher carrier mobility as well as lower contact resistance can be realized. This work opens a way for probing intrinsic properties of contaminant-free graphene and fabricating high-performance GFETs with both clean channel and intimate graphene/metal contact.The online version of this article (doi:10.1007/s40820-016-0093-5) contains supplementary material, which is available to authorized users. Beingctronics –6. UnforTo fabricate graphene field-effect transistors (GFETs), graphene grown by chemical vapor deposition (CVD) need to be transferred from a metal foil to an insulating substrate using a polymer such as poly(methyl methacrylate) (PMMA) as a support layer. PMMA is also commonly used as a mask material for electron beam lithography (EBL). Yet, a thin layer of PMMA residues (1–2 nm) after organic solvent  cleaning cannot be completely removed due to strong physical  or chemical  adsorption effects .2 atmosphere or vacuum [Previous studies show that polymer residues left on graphene surfaces result in shift of the Fermi level and decrease of carrier mobility , 5. Liker vacuum , 10, 11.2 plasma treatment is aggressive and needs to be operated with extremely low plasma density and delicate time control [However, previous studies of transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and electrical measurements reveal that thermal annealing still cannot remove the polymer residues thoroughly. Furthermore, high-temperature heating process may intensify graphene/substrate and graphene/atmosphere interactions, causing graphene to be highly doped with severe mobility degradation –13. In a control , 18; ult control , 20.Here we propose a new technique using a laser beam to eliminate polymer residues and recover clean graphene surfaces. Our laser cleaning technique, unlike previous methods, can be specially applied to targeted positions without introducing additional contaminants and defects. In the following contexts, detailed descriptions on laser cleaning process and optimization conditions are given. Then the laser cleaning technique is applied to GFETs, which shows that higher carrier mobility as well as lower contact resistance can be realized. Finally, mechanisms of laser cleaning are discussed in three ways: agglomeration, decomposition, and expulsion.2 layer. The CVD graphene films were grown on polycrystalline copper foil  in a gas mixture of methane, hydrogen, and argon at 1000 °C. Then graphene films were transferred to a Si/SiO2 substrate. To describe the process of laser cleaning, both the exfoliated and CVD graphene films on Si/SiO2 substrate were intentionally spin-coated with a 270-nm-thick PMMA layer (Allresist AR-P 679.04), baked at 170 °C for 2 min, cooled to room temperature, and then placed in an acetone bath for 2 h to dissolve PMMA. The number of layers was first characterized by optical microscopy (Olympus BX51) and then confirmed by Raman spectroscopy  and atomic force microscope  in air.Graphene was prepared using both mechanical exfoliation and CVD methods. The exfoliated graphene films were peeled off from natural flake graphite using an adhesive tape (3 M) at ambient conditions and transferred onto a heavily doped Si wafer coated with a 300-nm-thick thermally grown SiOBack-gated GFETs were fabricated in a top-down process. The graphene channels were patterned using e-beam lithography (EBL) followed by inductively coupled plasma reactive ion etching (ICP-RIE). The source (S) and drain (D) electrodes were fabricated by EBL, e-beam metal evaporation, and subsequent lift-off process. The exfoliated and CVD graphene films as the channel were contacted with Ti/Au (10/70 nm) and Pd/Au (20/60 nm), respectively. The structure of GFETs was inspected by optical microscope and AFM at tapping mode. All electrical measurements of GFETs were carried out on a probe station (Signatone WL-210E) using an Agilent B1500A semiconductor device analyzer under ambient conditions.2 substrate were 0.695, 1.041, and 4.826 nm, respectively . The PMMA residues on CVD graphene surfaces were introduced during the transfer process from Cu foil to SiO2 surface.Figure  . Also a piezoelectric multi-axis stage with variable step size  was mounted to locate or scan the graphene samples , which indicates that a nearly complete removal of polymer residues is achieved. The higher the exposure power, the faster the Rq decreases and saturates. However, it may induce defects at higher power . The dotted red boxes indicate the regions where the disorder-induced Raman D peak occurs. Figure −1 indicates that there is no significant damage to the sp2 hybridized carbon structure under a moderate exposure power of 30 mW for 180 s [−1 for monolayer GFETs to realize fast, effective, and noninvasive removal of polymer residues.To save time, we increase the exposure power of laser. The dependence of or 180 s . HoweverThis laser cleaning technique has also been applied to CVD mono-, bi-, and trilayer graphene, as shown in Fig. S3. The polymer residues left on CVD graphene samples are apparently removed, except at the ripples formed in wet transfer process where few residues may still remain due to increased chemical activity at these sites .2 substrate. Figure Vbg of the GFET before and after laser cleaning of the channel. Total resistance in our two-probe measurements is calculated from the transfer characteristics with Vbg swept from −40 to 40 V (Vds = 0.1 V). The as-fabricated GFET exhibited a shift of the charge neutrality point  to 26.4 V, owing to the hole doping by polymer residues from EBL process [Rtotal is the total resistance; Rcontact is the contact resistance; L and W are the channel length and width, respectively; μ is the carrier mobility; n0 is the carrier density at the Dirac point; n = Cbg(Vbg−VD) is the carrier density away from the Dirac point; and Cbg is the back-gate capacitance. There is a good agreement between measured data and theoretical fits as shown in Fig. 2 (Vs)−1, respectively. The electron–hole asymmetry is generally attributed to charge transfer at the interface of graphene/metal contact, which forms p–n or p–p junctions for electron or hole cases and results in different transport properties [VD shifted to 7.6 V, indicating reduction in hole doping. The near-zero yet non-zero VD is attributed to oxygen or moisture adsorption from ambient atmosphere [2 (Vs)−1, respectively. We measured eight GFETs before and after laser exposure. Histogram of electron (red) and hole (blue) mobility of these GFETs is shown in Fig. In the following, we demonstrate how this laser cleaning technique can be harnessed to remove PMMA contaminants from the graphene channel and graphene/metal contact in GFETs. For clarity, the effects of laser cleaning on graphene channel and contact were investigated independently. For the case of laser cleaning of the graphene channel, an exfoliated monolayer graphene was contacted by Ti/Au 10/70 nm) electrodes via EBL and lift-off metallization process to form a GFET. Figure  process . The ele process , 30:Fig.operties , 32. Aftmosphere , 33, 34./70 nm elThe laser cleaning technique can also be used to remove the polymer residues from the contact regions of GFETs as defined by EBL prior to metal deposition. The previous thermal or current annealing methods, however, are not possible to remove the residual PMMA layer that is already covered by metal. To form intimate graphene/metal contact without polymer residues, generally there exist two kinds of processes in previous reports: the resist-free process and the resist-involved process. However, the resist-free process includes complex steps of non-polymer mask fabrication and alignment , 35. The2 substrate by a PMMA layer and cut into a 1.4-μm-wide strip via EBL and inductively coupled plasma (ICP) etching. Then subsequently EBL was re-performed to define the electrode array. As shown in the middle inset of Fig. 12 and GFET34 with Vbg grounded. The device structure is shown in the lower inset of Fig. 12 with uncleaned contacts, the Id–Vd curve of GFET34 with cleaned contacts exhibits a steeper slope indicating a lower total resistance. As the two GFETs are fabricated adjacently from a same graphene strip with nearly identical geometry, the reduction in contact resistance is supposed to be the main contributor to the reduction in total resistance. Contact resistance, extracted from total resistance  is 390.1 and 87.8 Ω μm for uncleaned and cleaned GFETs, respectively. We measured five GFET groups with similar structure using the above local cleaning process. Figure CVD monolayer graphene was used to demonstrate the laser cleaning effects on contacts. The cleaning process at graphene contacts is as follows: first, a CVD graphene was transferred onto a SiOectively , 37. As It is worth noting that this laser cleaning technique may also be used in contact area with size smaller than 1 μm. The contact region shown in Fig. Besides PMMA residues, our laser cleaning is also effective for other polymer residues, such as novolak-based negative resist (AR-N 7520). After cleaning by 532 nm laser at 30 mW for 180 s, the residual negative-resist residues can also be completely removed, as shown in Fig. S4.Rq, as shown in Fig. 2, CO, CO2, CH4, C2H4) in trace amounts [The mechanism of our laser cleaning process can be understood based on laser ablation phenomenon and PMMA behavior under laser exposure. Laser ablation (commonly by ultraviolet or near-infrared pulse lasers) has been widely used and thoroughly investigated for polymer micro-machining since the early 80s . Here we amounts , 46, 47.On the other hand, during photon absorption, polymer residues not only gain energy but also momentum. Driven by monomer vapor pressure as well as laser light pressure, expulsion of liquid PMMA particles or even ejection of solid PMMA fragments occurs, thus facilitating removal of polymer residues , 48, 49.In summary, we have proposed a facile and reliable technique to remove polymer residues on graphene surfaces without generating defects using a visible laser from Raman system. After laser cleaning of the channel in GFETs, carrier mobility has been improved by a factor of 1.5–2.6. Moreover, this technique can be particularly applied to the contact regions as defined by EBL prior to metal deposition to eliminate the polymer residues, which is impossible by previous annealing methods. The contact resistivity of GFETs with cleaning at contacts can be reduced to 1/5–1/3 of those of GFETs without cleaning. This work provides an efficient route to get access to intrinsic properties of polymer residue-free graphene and fabricate high-speed GFETs with high carrier mobility and low contact resistance.Supplementary material 1 (PDF 805 kb)Below is the link to the electronic supplementary material.


Here we report on a miniaturized optical interferometer in one fiber based on two mismatched nodes. The all-fiber structure shows stable performance of temperature and humidity sensing. For temperature sensing in large ranges, from 40 to 100 °C, the sensor has a sensitivity of 0.24 dB/°C, and the adjusted R-squared value of fitting result reaches 0.99461 which shows a reliable sensing result. With carbon nanotubes coating the surface of the fiber, the temperature sensitivity is enhanced from 0.24561 to 1.65282 dB/°C in a small region, and the performance of humidity sensing becomes more linear and applicable. The adjusted R-squared value of the linear fitting line for humidity sensing shows a dramatic increase from 0.71731 to 0.92278 after carbon nanotube coating, and the humidity sensitivity presents 0.02571 nm/%RH. The detection of environmental parameters, including physical and chemical changes, has become increasingly important for process control, security monitoring, and human protection. Temperature and humidity are the key parameters in these applications because of their great influence on food safety, manufacturing accuracy, and the service lives of precise instruments. Various methods have been used for temperature or humidity sensing, such as physical methods ,2,3,4,5,2-hybridized carbon atoms [Carbon nanotubes (CNT), which were first discovered by Iijima in 1991, are known as 1D nanostructures with spon atoms . The stron atoms . CNT maton atoms ,26. Beneon atoms ,29,30,31A mismatched structured fiber was successfully fabricated to serve as our miniaturized optical fiber interferometer (MOFI). The offset of the two single fibers was around 20 μm, and the distance between the two nodes was about 2 cm. The multi-walled CNT were bought from a commercial corporation. The CNT were dispersed in ethanol solvent and attached to the fiber structure using the drop-cast method. In order to make sure that the CNT adhered to the fiber firmly, an annealing process was conducted from the temperature of 100 °C to room temperature (24 °C).To test the performance of the achieved mismatched fiber, and to explore the diverse potential applications based on light modulation by environment change, the experiments and comparison between the bare mismatched fiber and the CNT-assisted mismatched fiber were conducted on temperature and humidity sensing. The range of the temperature was controlled between 40 and 125 °C at an interval of 5 °C. The relative humidity (RH) sensing experiment was conducted by tuning RH between 45% and 95% at an interval of 10% at room temperature (24 °C). For each testing step of temperature and RH, extra observation time of 25 min was guaranteed to make sure that the results were stable and reliable. A wideband laser device (1300–1650 nm) was utilized as the light source, and the optical spectrum analyzer was used for spectra capture. The simulation work of the mismatched fiber structure was conducted, and the results are shown in Based on the MOFI structure, we can realize sensing performance through tuning light interference between the core mode and cladding modes which can be stably excited in the mismatched fiber structure. L is the interference length.L in Equation (3)), the wavelength shifting can also be attributed to alteration of the RI difference between core mode and cladding modes. The interference intensity will also be influenced by energy redistribution of core mode and cladding modes which is induced by RI change of fiber core and cladding. Based on the observation in the experiment process, the fiber condition can be stabilized within 90 s following the external environment change, which means that the response time of temperature sensing can be estimated to be 90 s. The sensitivity is calculated to be 0.2165 nm/°C which is almost four times higher than 0.0575 nm/°C reported by Dong et al. [The destructive interference condition is shown in the following equations :(2)2π⋅(ne rising . Howevere rising . This meg et al. . It was To increase the sensitivity of temperature sensing performance, the CNT material was utilized to alter the cladding modes modulation of the MOFI structure. As can be seen from Based on cladding modes modulation, this mismatched fiber structure can also be used for humidity sensing, as shown in Based on the above results, it is manifested that both the core mode and cladding modes can be excited in the mismatched fiber structure. This structure shows good and stable sensing performance of temperature and humidity which is due to the modulation of cladding modes by the external environment. Due to the dominant cladding modes, the all-fiber sensor shows good sensing reliability and sensitivity.In conclusion, a mismatched fiber structure was successfully created and simulated that demonstrated its application for sensing temperature and humidity based on cladding modes modulation. The sensing experiments were conducted with the structured fiber, and it displayed good temperature and humidity sensing performance. With CNT attached to the fiber, the sensitivity of temperature detection in small ranges was enhanced from 0.24561 to 1.65282 dB/°C, and the humidity sensing became more reliable for real application. The combination of the manufactured MOFI structure and CNT achieved cost-effective, sensitive, and reliable sensing for both temperature and humidity.


Discourse and argumentation are effective techniques for education not only in social domains but also in science domains. However, it is difficult for some teachers to stimulate an active discussion between students because several students might not be able to develop their arguments. This paper proposes to use WordNet as a semantic source in order to generate questions that are intended to stimulate students’ brainstorming and to help them develop arguments in a discussion session. In a study including 141 questions generated by human experts and 44 questions generated by a computer system, the following research questions have been investigated: Are system-generated questions understandable? Are they relevant to given discussion topics? Would they be useful for supporting students in developing new arguments? Are understandable and relevant system-generated questions predicted to be useful for students in order to develop new arguments? The evaluation showed that system-generated questions could not be distinguished from human-generated questions in the context of two discussion topics while the difference between system-generated and human-generated questions was noticed in the context of one discussion topic. In addition, the evaluation study showed that system-generated questions that are relevant to a discussion topic correlate moderately with questions that are predicted as useful for students in developing new arguments in the context of two discussion topics and understandable system-generated questions are rated as useful in the context of one specific discussion topic. An argument is an artifact that is created to articulate and justify claims, explanations, or viewpoints, and argumentation is the process of generating these artifacts  and Freebase (https://www.freebase.com/) to facilitate learners’ self-directed learning. Using this system, students in self-directed learning are asked to build a timeline of events of a history period with causal relationships between these events given an initial document. The student develops a concept map containing a chronology by selecting concepts and relationships between concepts from the given initial Wikipedia document to deepen their understanding. While the student creates the concept map, the system also generates its own concept map by referring to semantic information from DBpedia and Freebase. The system’s concept map is updated with every modification of the student’s one and enriched with related concepts that can be queried from both linked open data sources. Thus, the system’s concept map always contains more concepts than the student’s map. Using these related concepts and their relationships, the system generates questions for the student to lead to a deeper understanding without forcing to follow a fixed path of learning.In contrast to traditional approaches to generating questions using text as input and deploying various natural language processing techniques for creating questions, the fifth class of educational applications of question generation exploits linked open data that are a part of the semantic web  With respect to the technical issue, while Jouault and Seta adopted ontology and linked open data techniques to eliminate the difficulty of the natural language understanding problem in the learning domain , this paper suggests an approach to deploy natural language techniques  in order to extract important concepts from a discussion topic and using WordNet to query related concepts that are relevant for discussion; 2) With respect to learning goals, Jouault and Seta proposed to use automatic generated questions for enhancing students’ knowledge in history whereas our approach focuses on helping students develop new arguments for the argumentation process.The catastrophe at the Fukushima power plant in Japan has shocked the world. After this accident, the Japanese and German governments announced that they are going to stop producing nuclear energy. Should we stop producing nuclear energy and develop renewable energy instead?In this section, we describe conceptually how questions can be generated in our approach. A more detailed technical description of the approach is presented in Le et al. . In ordecatastrophe, Fukushima power plant, nuclear energy, renewable energy. This step is described in more details in the following subsection.From the discussion topic, we note that the following noun phrases can serve as starting points to generate questions: In order to automatically recognize key concepts of a discussion topic, a natural language parser is used to analyze the grammatical structure of a sentence into its constituents. The language parser analyzes a text and identifies the category of each constituent . This parsing process results in a parse tree. Since nouns and noun phrases can be used as key concepts in a discussion topic, we select from the parse tree of the parsed discussion text only constituents which are tagged as nouns (NN) or noun phrases (NP) cf. Fig. . Since tWhat does <X> remind you of?What are the properties of <X>?What is an example of <X>?Using the extracted key concepts, we are ready to generate questions. The next issue that needs to be addressed is to determine the types of questions to be generated. According to Wilen , there ehttps://www.wikipedia.org/) provides descriptions of concepts. While Wikipedia might contain incorrect information due to its contribution mechanism, one of the advantages of Wikipedia is that the description of many concepts is available in many different languages. If we want to develop a question generation for different languages, Wikipedia might be an appropriate source. WordNet  responded to Europe's debt crisis by flooding banks with cheap money…ECB President has reduced the main interest rate to its lowest level in history, taking it from 0.5 to 0.25 percent” , this might make it difficult for discussion participants to initiate a discussion or for human experts to think of questions to be generated:From our eight experts, we received 54 questions for topic 1, 47 questions for topic 2, and 40 questions for topic 3.For each discussion topic, the system generated several hundred questions , because from each discussion topic several key concepts were extracted, and each key concept was extended with a set of hyponyms queried from WordNet. For each key concept and each hyponym, fourteen questions have been generated based on the question templates in Table Then, we mixed human-generated questions with automatic generated questions and asked human raters to identify whether each question from the mixed set of questions had been generated by the system or by a human expert. For topic 1, we had three raters, and for each of the last two topics, we could only get two raters. Note that these human raters were not the same human experts who generated questions. Also, they did not know about the proportion between human-generated questions and system-generated questions.Is that an automatic system-generated question (Yes/No)? We use the balanced F-score to evaluate and to analyze the ratings of humans. The F-score is calculated based on precision and recall using the following formula:First, we evaluated the soundness of system-generated questions. For this purpose, we asked human raters to answer the following question: F-score is high, it shows that the system-generated questions and the human-generated questions are easy to distinguish. Otherwise, a low F-score indicates that it is difficult for human raters to distinguish between system-generated and human-generated questions.The precision for a class is the number of true positives  divided by the total number of elements labeled as belonging to the positive class, while the recall for a class is the number of true positives divided by the total number of elements that actually belong to the positive class. If the F-scores of each human rater. It shows that for topic 1, it was difficult for rater 1 (F = 0.33) and moderately difficult for rater 2 (F = 0.51) to distinguish the authorship of questions. The kappa value (0.086) indicates a low agreement between two raters—which means that even if each of the graders correctly classified some questions, their ratings would not be consistent with each other. With respect to topic 2, the F-score of both raters is moderate (0.5 and 0.52). The Kappa value for their agreement was 0.233, which can be considered as fair. This shows that for topic 2, it was easier to distinguish between human-generated and system-generated questions than in the context of topic 1. With respect to topic 3, for both raters, it was relatively difficult to identify the authorship of the questions (F-score is between 0.40 and 0.44) and the agreement between the raters was fair (0.263).Table What is cheap money?” was generated by a human expert and by the system identically. This question was assumed by both human raters as a system-generated question. Thus, this question was not included in the statistical evaluation for topic 3.Interestingly, in the context of topic 3, one question “In summary, we have learned that for all raters it was not easy to identify system-generated questions from the set of mixed questions. This indicates that system-generated questions are sound as human-generated questions. The agreement between raters was slight or fair. This strengthens the indication that it was difficult for human raters to distinguish between system-generated and human-generated questions.The goal of the following evaluation is to empirically investigate the first three research questions specified in the “The first three research questions were also given literally to human raters who were asked to rate the mixed set of questions using the scale from one to three scores . First, we investigate these research questions in the context of each specific discussion topic, then we normalize the evaluation result for each topic and investigate these research questions in general.In the context of topic 1, Table What do you have in mind when you think about tsunami?What do you like when you think of/about catastrophe?What does Fukushima remind you of?What does power plant remind you of?What features does catastrophe have?Analyzing the system-generated questions in the context of topic 1, we learned that there was no question that was rated with score 1  on average. The list of system-generated questions that have the rating score of 1.33 on average with respect to “Usefulness” follows:Should we stop producing nuclear energy and develop renewable energy instead”). If the questions were more specific, for example, “What does the catastrophe at the Fukushima power plant in Japan remind you of?”, this could be more useful.The low usefulness of these questions might be attributed to the fact that these questions are very general and have little relation to the question in the discussion topic 1 (“t = 3.01), relevance (t = 3.93), and usefulness (t = 3.29). Thus, the research hypothesis that system-generated questions are understandable, relevant to a given discussion topic, and useful for developing new arguments as human-generated questions cannot be confirmed in the context of topic 2.In the context of topic 2, Table deflation be used today?” It is not common for us that deflation can be “used” (unless we are economy experts). The other problem with these questions is that these “non-meaningful” nouns/noun phrases are extracted from the discussion topic  and from the hyponym set provided by WordNet . This is a limitation of the question generation approach presented in this paper. In the current version, the system is not implemented with a mechanism to identify meaningful noun phrases from the set of noun phrases that are extracted from a discussion topic and from the hyponym set of WordNet.We investigated the system-generated questions which had least mean score, i.e., the rating mean score over the raters is 1. Table Similar to topic 1, in the context of topic 3, Table (opposite-) problems” that is generated by the system using a pre-specified question template. The question could be more understandable if it were constructed like this: “How could problems of the central bank be stopped?” Thus, the pre-specified question template should be optimized accordingly. The problems with the two least relevant questions can be explained by the noun phrases “ECB president” and “central bank” that are not as relevant as other noun phrases “debt crisis” and “cheap money” in topic 3. Again, the problem here is to determine the most important noun phrases in a discussion topic before applying question templates for constructing questions. The least useful question “What features does ECB president have?” was also rated as least relevant. In In the “We analyze the system-generated questions with the lowest scores. We identified one least understandable, two least relevant, and one least useful question(s) Table . The leaWhat is cheap money?” that was generated identically by a human expert and by the system was rated by both human raters as very understandable. However, with respect to the criteria “Relevance” and “Usefulness”, there was disagreement between raters as Table The question “Overall, when considering the quality of system-generated questions over all three topics, we can learn from Table In this section, we investigate the fourth research question: Are understandable and relevant system-generated questions also useful for students?r = 0.76). A similar tendency can be found for human-generated questions (r = 0.81). Both correlation values are significant. However, the understandable system-generated questions are weakly correlated with the criterion of usefulness (r = 0.31), whereas for human-generated questions the correlation between the criteria understandability and usefulness is higher (r = 0.57).In the context of topic 1 . Yet, correlation values show that understandable questions (either system-generated or human-generated) are moderately correlated with the criterion of being useful questions (r = 0.52–0.53) and these correlation values are significant.In contrast to topic 1, in the context of discussion topic 2 (cf. Table r = 0.39–0.43). However, it indicates a weak relationship between understandable questions and useful questions. The correlation between the relevance of a question and its usefulness (r = 0.53–0.62) is moderately positive and means there is a tendency that relevant questions will be useful for students. Note, except the correlation coefficient between the criteria understandability and usefulness for system-generated questions, all other correlation values are significant.In the context of topic 3  are significantly correlated with useful questions, except the system-generated questions for topic 3. Relevant questions (both system-generated and human-generated questions) are significantly correlated with useful questions, except for topic 2.The question generation approach has been evaluated using three discussion topics from the domains of energy (topic 1) and economy (topics 2 and 3). Each topic was presented by two sentences that describe the problem of a topic, followed by a discussion question. With two discussion domains, we still cannot conclude about the coverage of scope of discussion domains that can be supported by the question generation system using WordNet. However, the results of the evaluation study give us some information about the quality of system-generated questions. In the context of topic 1, the human-generated questions were not significantly better than system-generated questions over three criteria “Understandability” and “Relevance” . In the context of topic 3, the difference between human-generated questions and system-generated questions was not significant over three criteria. Only in the context of topic 2, which is about increasing fear of deflation in Europe and US, the difference between human-generated and system-generated questions was statistically significant, i.e., the quality of human-generated questions was better than of system-generated questions. Of course, the effectivity of our approach relies on the set of hyponyms provided by WordNet and on the accuracy of the algorithm that extracts nouns/noun phrases from a discussion topic.In the current implementation of the system, the algorithm for extracting nouns/noun phrases from a discussion topic has the limitation that it is not able to rank the importance of a noun/noun phrase. In order to determine the relevance of a concept, several effective approaches have been devised in the area of information retrieval, e.g., document frequency  for evaluation without having clear selection criteria. The small number of selected system-generated questions and the ratio 1:3 between system-generated questions and human-generated questions might not reflect fully the quality of system-generated questions. We might think of increasing this ratio. Yet, possibly too many system-generated questions might bias human graders—this needs to be investigated.This paper presented a question generation approach using WordNet for supporting students during argumentation processes. The approach extracts important concepts from a discussion topic and query hyponyms of these concepts from WordNet. Questions are constructed by either using important concepts from a given discussion topic or using hyponyms of the extracted concepts.Although the evaluation results show that system-generated questions were as sound as human-generated questions in two discussion topics, the question generation approach presented in this paper certainly still has some limitations. First, it generates too many questions for a discussion topic. Second, the algorithm for extracting relevant concepts is not yet able to determine the grade of importance for each noun/noun phrases. These two issues are our short-term future work.As long-term future work, we intend to use system-generated questions and human-generated questions of highest quality to test whether they are actually useful for students in the argumentation process. After that, we intend to identify and model characteristics of useful questions for argumentation purposes. Using this model, appropriate question templates will be defined for question generation.


In earlier studies, much research has focused on increasing the efficiency of heat exchanger fields. Therefore, in this study, graphene nanofluid was fabricated for use as a heat transfer medium for a heat exchanger. Graphene has excellent electrical conductivity, mechanical properties, and heat transfer properties. It is expected that the heat transfer efficiency will be improved by fabricating the nanofluid. However, graphene is prone to sedimentation, because of its cohesion due to van der Waals binding force. In this experiment, a nanofluid was fabricated with enhanced dispersibility by surfactant and the ball-milling process. The zeta potential, absorbance, and thermal conductivity of the nanofluid were measured. As a result, when using the ratio of 2:1 (graphene:sodium dodecyl sulfate (SDS)), a higher thermal conductivity was obtained than in other conditions. As the industry has developed, heat exchangers have been increasingly used in a variety of fields, including food, cooling and heating, shipbuilding, and chemistry. Thus, if the efficiency of the heat exchanger can be increased, the energy consumed and the generation of carbon dioxide can both be reduced ,2. Commo2/g and purity of 99.9% was purchased from Graphene supermarket, and surfactant SDS and SDBS were purchased from Junsei Chemical Co., Ltd.  (SDS), TOKYO Chemical Industry Co., Ltd.  (SDBS) was used. First, 0.1 g of graphene was pulverized with a ball size of 1 mm, a ball-milling speed of 200 rpm, and a ball-milling time of 60 min using (a) the planetary ball mill instrument. After that, the ratio of graphene (0.1 wt %) dissolved in the water and the surfactant SDS and SDBS were prepared for adding in ratios of 1:3, 1:2, 1:1, 2:1, and 3:1. Furthermore, ultrasound excitation was carried out for 40 min to make the graphene nanofluids, and the degrees of nanoparticle dispersion were measured by using UV spectroscopy.In this study, DW (distilled water) was used for the base fluids that were produced through the membrane-type DW maker, which maintained a water quality under 10 ppm for the total dissolved solids (TDS). Graphene with 7-nm thickness and a 40-nm size with a specific surface area of 100 mThe equipment used in this experiment is shown in The thermal conductivity measuring system LAMBDA in A graph of the zeta potential, which was measured using a ZetaSizer Nano ZS instrument, is shown in The mean thermal conductivity of the graphene nanofluids according to the amount of surfactant added is shown in In this study, graphene was grinded using a planetary ball mill instrument to stably disperse and the graphene nanofluid; (0.1 wt %) graphene nanofluid was prepared by adding surfactant to each condition. In order to measure the dispersion and dispersion stability, the zeta potential and the absorbance through UV were measured. The thermal conductivity was measured using the transient hot-wire method, and the following conclusions were obtained.(1)The absorbance was measured to confirm the dispersibility. The highest absorbance was obtained when 0.3 g of SDS and SDBS were used, and the lowest absorbance was obtained when 0.034 g of SDS and SDBS were used. As a result, as the surfactant ratio increases, the nanofluid containing SDS and SDBS produced higher absorbance values.(2)The zeta potential was measured to figure out the dispersion stability. Absolute values of 30 mV or more were obtained under all of the conditions, and it could be judged that the value of the dispersion stability was sufficiently high. In this experiment, SDBS showed that the zeta potential value was higher than SDS, and had a higher dispersion stability as the amount of surfactant was increased.(3)The thermal conductivity was measured in comparison with distilled water. Graphene nanofluid with SDS added showed a higher thermal conductivity than when SDBS was added. SDS showed a higher thermal conductivity than distilled water at the ratio of graphene to surfactant of 2:1 (0.05 g) and 3:1 (0.034 g) and generally, SDBS showed a lower thermal conductivity than distilled water at all of the conditions. When the mean thermal conductivity of the two surfactants was compared, SDS showed a higher increase in thermal conductivity than the SDBS as the amount of surfactant decreased. When the ratio of graphene to SDS was 2:1 (0.05 g), it showed the highest thermal conductivity. As a result of thermal conductivity measurement, it was confirmed that the thermal conductivity becomes smaller according to the amount of the surfactant.


Efficient reduction of graphene oxide to obtain high-quality graphene nanosheets is desirable for energy storage, catalysis, electronics and environmental remediation. In this brief review, we mainly focus on the microwave-assisted production of reduced graphene oxide in three categories: (1) microwave-assisted chemical reduction of graphene oxide; (2) microwave-assisted thermal reduction of graphene oxide; (3) microwave-assisted simultaneous thermal exfoliation & thermal reduction of graphite oxide. We also summarize common techniques for characterizing reduction efficiency and quality of as-obtained rGO. In general, there are mainly two strategies used for graphene oxide reduction: chemical reduction and thermal reduction, both of which are facing certain challenges. In chemical reduction methods, the reduction efficiency is unsatisfactory, requiring long treating time and yielding rGO with oxygen content usually higher than 15%  pattern of graphene/graphite oxide usually shows a characteristic diffraction peak at 2θ = 10.9° with the corresponding d-spacing of 0.81 nm  could help to obtain qualitative and quantitative analysis results of the content of oxygenated groups. For example, the carbon/oxygen atomic ratio (C/O ratio) could be evaluated from the areas of C1s and O1s peaks and the atomic sensitivity factor. Usually, the C/O ratio of graphene oxide is ~2.2–2.7  solution. Zhao et al.  is usually required, which is not only very energy consuming but also leads to the formation of defects in the graphene basal plane because of the evolution of the oxygen functional groups during reduction, like nanoscopic holes brought by carbon loss as CO or CO2 and Stone-Wales types of defects lead by rearrangement of carbon atoms in the graphene basal plane. Besides, the reducing efficiency is always suppressed by the highly stable ether and carbonyl groups formed between the oxygen functional groups.In conventional thermal reduction process, long-time high-temperature treatment in a protecting atmosphere  of rGO prepared by 800°C annealing. They further examined the Raman spectra of graphene-triggered microwave reduction at different positions, and found the part of graphene oxide located nearest to the trigger was not reduced the best, as shown in Jiang et al.  further Instead of putting a small piece of graphene as the trigger, Wan et al.  put a fuD/IG in the Raman spectrum of the product decreased from 2.89 to 1.56 and C/O derived from XPS results increased from 7.8 to 17.5. In addition, microwave-enabled exfoliation leading to thinner pieces was also observed in their work.Low-temperature reduction of graphene oxide is of great importance when graphene oxide film was deposited on glass or plastic substrates. Han et al.  demonstrD/IG values, the high C/O values and the conductivity values of most as-derived rGO. It is worth to note that rGO containing only 4% oxygen and exhibiting pristine CVD graphene-like features in the Raman spectrum was successfully fabricated via this reducing strategy. Besides, owning to the ultra-rapid treating process, protecting atmosphere is not always necessary. However, too long treatment time would result in re-oxidation and consequently rGO with worse quality when the reduction is done in the air. Since the amounts of GO samples and the microwave heating chambers in different work were different, which would affect the power intensity imposed on the GO, it is also difficult to draw a conclusion regarding the effect of microwave power here.The characteristics of the as-obtained rGO products derived from different microwave-assisted thermal reduction of graphene oxide methods are summarized and listed in −1.Beside of direct reduction of graphene oxide to yield rGO, thermal shock like flash-assisted simultaneous exfoliation and reduction of graphite oxide at temperatures up to 1,050°C has also been used. Theoretically, microwave heating which is well-known for its rapid heating feature is very promising in enabling simultaneous exfoliation and reduction of graphite oxide. In 2010, Zhu et al.  treated Under microwave irradiation, graphite oxide itself might not be heated to a high enough temperature to cause its exfoliation and reduction efficiently due to its inferior microwave absorption ability. Scientists have tried several ways to come over this problem.2+Ar (1:9) showed a C/O ratio of 3.6, 11.45, 18.5, respectively and ID/IG values of 0.853, 0.842, and 0.785, respectively in Raman spectra, respectively. The rGO prepared in Ar, H2+Ar showed a conductivity of 7.41 × 102 and 1.25 × 103 S m−1, respectively. Hydrogen containing atmosphere is the most effective because H2O was formed instead of CO2, which prevents the formation of vacancies and defects due to the loss of carbon atoms.Park et al.  mixed gr4 at 95°C for 2 h, and subsequently made into a film, which was microwave irradiated at 5.8 GHz with a power of 1,400 W for 10 min in N2. After NaBH4 treatment, a C/O value of 3.84, an ID/IG value of 1.05 in Raman, and a conductivity of 1.41 × 102 S m−1 were obtained. During the microwave treatment, the sample expanded to a loose floc and transmitted bright orange light, leading to ultrathin sheets with a C/O ratio of 10.33, an ID/IG ratio of 1.07 in the Raman spectrum and a conductivity of 1.19 × 104 S m−1. Sole microwave irradiation at 5.8 GHz with a power of 1,400 W for 10 min without a preceding chemical reduction process gave yield to a C/O of 7.24 and an ID/IG of 0.89 in Raman spectrum. This demonstrated that solid-state microwave irradiation not only removed oxygen-containing groups, but also repaired defects on the graphene sheets while NaBH4 though effective for removing oxygen-containing groups may induce more defects. Further, through XPS analysis of content of C-O and C = O groups, they found that microwave irradiation removed C = O more readily than C-O while the chemical reduction method removed C-O more efficiently.Wen et al.  applied 2 without becoming red. The expanded graphite oxide had a C/O of 2.42. However, it was so loose that microwave could not concentrate on a definite area for further reduction of graphite oxide. Hence, in the second step, the expanded graphite oxide was collected and then exposed to additional microwave irradiation for 1 and 2 min, resulting in rGO showing a C/O ratio of 5.78 and 10.39, respectively.Pokharel et al.  developeD/IG values, mass loss temperatures and conductivities, simultaneous exfoliation and reduction was not able to yield rGO with as high quality as those obtained from thermal reduction of graphene oxides. However, when combined with reducing atmosphere  or pretreatment with strong reducing reagents (NaBH4), the reduction degree could be greatly enhanced.The characteristics of the as-obtained rGO products derived from different microwave-assisted simultaneous thermal exfoliation and reduction of graphite oxide methods are summarized and listed in It is expected that the explored methods for microwave-assisted reduction of graphene/graphite oxide into high-quality rGO could be extended to fabrication of graphene composites. The microwave-induced arc facilitated short reaction time at high temperature is not only beneficial for getting high-quality rGO, but also promising in facilitating the formation of high-quality nanomaterials  with advanced performance. In addition, the methods could be extended to fabrication of other conductive materials that could trigger sparks under microwave irradiation, like graphene does.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.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.


LINE‐1 or L1) reactivation is linked to poor prognosis in non‐small‐cell lung carcinoma (NSCLC), but the molecular bases of this response remain largely unknown. In this report, we show that challenge of human bronchial epithelial cells (HBECs) with the lung carcinogen, benzo(a)pyrene (BaP), shifted the L1 promoter from a heterochromatic to euchromatic state through disassembly of the nucleosomal and remodeling deacetylase (NuRD) complex. Carcinogen challenge was also associated with partial displacement of constituent proteins from the nuclear to the cytoplasmic compartment. Disruption of NuRD corepression by genetic ablation or carcinogen treatment correlated with accumulation of L1 mRNA and proteins. Mi2β bound directly to the L1 promoter to effect retroelement silencing, and this response required the DNA‐ and ATPase‐binding domains of Mi2β. Sustained expression of L1 in HBECs was tumorigenic in a human–SCID mouse xenograft model, giving rise to tumors that regressed over time. Together, these results show that functional modulation of the NuRD constituent proteins is a critical molecular event in the activation of L1 retrotransposon. L1 expression creates a microenvironment in HBECs that is conducive to neoplasia and malignant transformation.Long interspersed nuclear element‐1 ( BaPbenzo(a)pyreneHBECshuman bronchial epithelial cellsLine‐1/L1L1)long interspersed nuclear element‐1 L1 is ~6 kb and consists of an internal promoter located within the 5′untranslated region (5′UTR), two open reading frames (ORFs) encoding ORF1p and ORF2p, and a 3′UTR with a poly(A) tail and signal  at 711 (t/c), both of which differentiate Ta‐1d from the Ta‐Ind, Ta‐0, and Pre‐Ta families  or trans‐ (minor) preference to bind L1 mRNA or SINEs and other cellular mRNAs, to form ribonucleoprotein particles (RNPs) pyrene (BaP) through a process that is orchestrated by the aryl hydrocarbon receptor (AHR) and retinoblastoma (RB) family of proteins to influence the epigenetic machinery , as seen in non‐small‐cell lung cancers (NSCLCs)  through a signaling cascade initiated by TGF‐β1  multiprotein complex is enriched in the 5′untranslated DNA sequence of L1 in human and murine cells. Further, genetic ablation of RB proteins destabilizes interactions within the NuRD complex, and mediates nuclear rearrangement of Mi2β, an ATP‐dependent helicase subunit with nucleosome remodeling activity ; methyl‐CpG‐binding domain proteins 1/2/3 (MBD1/2/3); metastasis‐associated proteins 1/2/3 (MTA1/2/3); histone‐binding proteins , histone deacetylases 1/2 (HDAC1/2), and nuclear zinc finger proteins (Gata2a/2b(p66α/β))  vector using infusion cloning and primers listed in Table CTR or pB015WT using Lipofectamine, as previously described. The pB015WT and pB001CTR  vectors were used to create stably transfected HBECs constitutively expressing L1‐ORF1 and ORF2 proteins, as confirmed by indirect immunofluorescence.Mi2β wild‐type (WT) and a biologically inactive W508A chromodomain mutant were kind gifts from J. Hagman at the University of Colorado . A polyclonal antibody against L1‐ORF1 generated by New England Peptide and validated in previous studies was used in all experiments  is a nontransformed HBEC line immortalized with a replication‐defective SV‐40/adenovirus 12 hybrid . Despite the presence of T‐antigen in replication‐defective lines . Chromatin immunoprecipitation assay (ChIP) was conducted as described before , vortexed briefly, and incubated at room temperature for 15 min with gentle rotation. The eluate was combined with 20 μL of 5M NaCl and incubated at 65 °C for 4 h to reverse formaldehyde cross‐linking of DNA/protein complexes. DNA was recovered by phenol/chloroform extraction and ethanol precipitation. DNA was resuspended in nuclease‐free H2O and quantified by Cytation 3 machine. Serial dilutions were completed to confirm a linear relationship while accounting for proper amplification of template to ensure equal amounts of starting template for all samples. RT‐PCR was used to determine enrichment for L1‐5′UTR sequences using tiling primers (P1‐P4) that span the 5′UTR promoter region of L1. The specificity of NuRD target recognition was examined in previous studies  supplemented with protease and phosphatase inhibitor cocktails (Cat#: 539‐134‐1SET) before being scraped and pelleted for 5 min at 800 g at 4 °C and resuspended in DPBS. Two 500‐μL aliquots of lysate were set aside for RNA analysis and input control. A total of 500 μL of lysate was resuspended in FAIRE lysis buffer  and sonicated as described for 30 sec and cooled in ice for ~5 min. Unbound DNA and DNA cross‐linked to proteins were separated by phenol/chloroform extraction. Unbound DNA in the aqueous phase was ethanol precipitated with 1/10 of 3M sodium acetate (NaAc) and 2.5X of 95% ethanol (ETOH) overnight followed by centrifugation at 14000 g for 20 min. DNA was washed with 70% ETOH once, air‐dried, and resuspended in 50 μL of sterile nuclease‐free H2O. Total DNA was quantified and serial dilutions of 2.5, 5, and 10 ng used for RT‐PCR analysis using a primer set (P4) that spans the CpG shore region of the L1 promoter . Total gDNA for use as input control was isolated using Purelink genomic DNA isolation kit (Cat#: K1820‐01).Formaldehyde‐assisted isolation of regulatory elements (FAIRE) was used to study m HEPES/150 mm NaCl, pH 7.05). Retroviral packaging vectors (pSPAX‐2 and pVSV‐G) were a kind gift from Schenten at the University of Arizona . An aliquot of 42 μL of PEI (1.0 μg/μL) was added to each transfection and incubated at room temperature for 15 min. DNA/PEI complexes were added to the cells and incubated for 18 h. Transfection media were removed and new media containing 10% FBS added. The viral supernatant was collected the next day and filtered through 0.45‐μm PES filter tubes. Viral titer was incubated with one volume of X‐concentrator (Clontech) overnight and centrifuged at 1500 g for 45 min. The supernatant was removed and virus resuspended in 100 μL PBS to make 10X viral concentrate. A total of 10 μL of viral titer was used to transiently transduce transfected cells. HBECs were grown to 70% confluence and transiently transfected with 0.75 μg of luciferase and 0.25 μg of Renilla vectors. Transfection media were removed 18 h later. Cells were allowed to recover for 24 h and then transduced with Mi2βWT or mutant retroviral vectors or cotreated with BaP and retroviral vectors for 24 h. Cells were lysed passively for 15 min at room temperature and luciferase and Renilla luminescence measured using a Cytation 3 machine. Relative luminescence units (RLU) were calculated as a ratio of firefly luciferase to Renilla.HEK293T‐17 cells were used to generate virus titers for subsequent transduction of the virus containing Mi2β and mutant plasmids into BEAS‐2B cells. HEK293T‐17 cells were grown to 90% confluence and transfected with Mi2βWT/mutants retroviral vectors (6 μg), combined with pSPAX‐2 packaging vector (3 μg) and pVSV‐G envelope vector (1.5 μg) diluted in 500 μL of dilution media (10 m6) cells stably expressing control (pB001ctr) or wild‐type (WT) L1 plasmids (pB015wt) were mixed with Matrigel and injected subcutaneously into anesthetized SCID mice at the University of Arizona Cancer Center Core Facility. Mouse weights and tumor burden were monitored twice weekly for up to 90 days, with tumor volumes estimated using the following formula: [(width)2 × length]/2. A 1 : 50 dilution of ORF1p antibody was used to monitor L1‐ORF1 protein in tumors derived from grafted cells or human tissues by immunohistochemistry (IHC). Images were taken using an Axiovision inverted microscope at 40 ×  magnification.HBECs  and histone‐4 lysine‐20 trimethylation (H4K20Me3) . Marked reductions in enrichment for Mi2β, MBD2/3, and MTA2 were seen 12 h after carcinogen challenge, indicating that BaP displaces NuRD macromolecular complex constituents from the L1 promoter. Next, FAIRE was employed to separate unbound and bound DNA sequences based on their relative affinities for the aqueous and organic phases, respectively . Increased fluorescence intensity for cytoplasmic Mi2β and MTA2 was observed in cells treated with BaP compared to DMSO controls  that spanned the complete L1‐Ta 5′UTR promoter sequence coupled with antibodies specific to Mi2β  were transiently transfected into HBECs. Cells recovered from transfection for 24 h before treatment with retroviral vectors encoding Mi2βWT or mutants for an additional 24 h. Transduction efficiency was optimal 24 h after exposure (data not shown). A significant, but modest, reduction in L1 reporter activity was seen in Mi2β WT‐transfected cells  or a constitutively active wild‐type L1 construct (pB015WT) (n = 15)  and flag‐myc double tags, respectively . L1 was tumorigenic in SCID mice, with tumor burden first detected one week after inoculation and sustained for up to eight weeks . Representative samples are shown in Fig. L1‐ORF1 protein were detected in p53 null tissue, but not in normal lung. These findings demonstrate that activation of L1 in HBECs creates a microenvironment that supports oncogenic transformation and implicate molecular interactions between L1 and p53 as critical players in lung cancer.The final set of experiments examined the oncogenic potential of 8 h Fig. , an in vely Fig. A. A cytoeks Fig. B. No tument Fig. B. The exype Fig. C. L1‐ORFL1‐Ta reactivation, and malignant transformation in HBECs challenged with the lung carcinogen BaP. These findings build upon earlier reports by our group showing that L1 reactivation involves the following: 1) enrichment of activating H3K4Me3 and H3K9Ac marks; 2) increased histone H3 acetylation of the 5′UTR; 3) reduced DNMT1 recruitment; and 4) CpG hypomethylation in both transformed and nontransformed epithelial cells . As such, constitutive AHR may support critical protein–protein interactions that are disrupted in the presence of BaP to facilitate disassembly of the NuRD repressor complex. Furthermore, AHR interacts with TGF‐β1, an upstream regulator of L1 and inducer of EMT in HBECs  pathway (Wylie et al., L1‐encoded ORF‐1p was increased in human lung tumors null for p53, a finding consistent with previous reports (Wylie et al., L1 can induce tumors in athymic mice that outgrow those induced by wild‐type L1 (Reyes‐Reyes et al., L1 pose significant restrictions on the tumorigenic process. This is an area worthy of exploration as novel chemotherapeutic agents can be designed to exploit this property in the clinical management of lung tumors.Interestingly, tumor growth in mice grafted with cells expressing L1‐Ta promoter from a heterochromatic to euchromatic state through disassembly of the NuRD complex and partial displacement of constituent proteins from the nucleus to the cytoplasm. Disruption of NuRD corepression correlates with accumulation of L1 mRNA and proteins and tumorigenesis.In conclusion, evidence is presented here showing that challenge of HBECs with the lung carcinogen BaP shifts the KSR conceived the study, KSR and PBJr designed the study, PBJr acquired the data, KSR and PBJr analyzed and interpreted the data, and KSR and PBJr wrote the manuscript.Fig. S1. Optimization of L1‐ORF1 in HBECs by Western analysis.Fig. S2. Time‐dependent analysis of L1 mRNA accumulation in HBECs challenged with 0.1 μm BaP.Fig. S3. DNA and Sequence analysis of L1‐5′UTR sequences.Fig. S4. Analysis of CYP1A1 expression after 12 h of BaP treatment by indirect immunofluorescence.Click here for additional data file.


Graphene, a single atom thick layer of two-dimensional closely packed honeycomb carbon lattice, and its derivatives have attracted much attention in the field of biomedical, due to its unique physicochemical properties. The valuable physicochemical properties, such as high surface area, excellent electrical conductivity, remarkable biocompatibility and ease of surface functionalization have shown great potentials in the applications of graphene-based bioelectronics devices, including electrochemical biosensors for biomarker analysis. In this review, we will provide a selective overview of recent advances on synthesis methods of graphene and its derivatives, as well as its application to electrochemical biosensor development. We believe the topics discussed here are useful, and able to provide a guideline in the development of novel graphene and on graphene-like 2-dimensional (2D) materials based biosensors in the future.  This feature includes a high surface area, excellent electrical conductivity, strong mechanical strength, unparalleled thermal conductivity, and ease of surface functionalization  layer of a hexagonal structure consisting of splization  . Th. Th2O2 coflowers . The golng cells . A simplhydrogel . The devDifferently, Lee et al., utilized graphene-Au hybrid nanoelectrode array (NEAs) to monitor stem differentiation in a non-destructive real-time manner  89]. Ty. Ty89]. It is evident that the exceptional physicochemical properties of graphene and its derivatives make them compelling for various electrochemical biosensor applications. The development and wide application of the electrochemical sensing based on these materials were hindered by the lack of facile and reproducible synthesis method of these materials with defined properties. In order to make it compatible to develop various electrochemical sensors, numerous efforts have been devoted to controllable and scalable production of graphene and its derivatives. Mechanical exfoliation method was first used to obtain graphene; however, the poor controllability and low production were the limiting factors. To achieve scalable production, LPE based methods were developed to obtain a dispersed solution of these materials and its products has been the most widely utilized for the electrochemical biosensors. More or less, recently CVD method was also adopted to synthesize graphene with controllable properties; however, limited scale production of graphene and its derivatives still hinders its applications. For example, various oxygenated surface functional groups provide a relatively high surface area, while it inhibits the performance of electrochemical biosensor as an insulator. Thus, a novel synthesis method which can consistently produce graphene and its derivatives with defined properties  in a large scale (high yield) and cost-effective manner is still required for future commercialization of graphene and its derivatives based electrochemical biosensors.During the past years, many different strategies have been also explored to develop novel graphene and its derivatives based electrochemical biosensors for analyzing bio/chemical molecules. It is clear that the optimization through the selection of a suitable surface functionalization method still needs to be revealed, in order to develop a highly effective and reproducible electrochemical biosensors. In addition, the combination with functional materials, such as ionic liquids, nanomaterials and polymers, have provided numerous choices to take the synergistic effect to enhance the electroanalytical performances. However, designing and finding the appropriate combinatorial structure with functional materials must be addressed for each biomolecule to maximize the performance of electrochemical biosensors. Although extensive studies have been made to design and fabricate novel electrochemical biosensors, long-term stability of combinatorial structure and functionalized surfaces (with receptor), in complexed real sample matrices, should be considered. Real biological fluids, such as blood and plasma, always contain various molecules and ions which can cause the interference through nonspecific binding events and undermine the performance of electrochemical biosensors. Furthermore, to adopt graphene and its derivatives for recently arisen in situ live cells and in vivo sensing strategies, more effort, such as long-term toxicity of graphene and its derivatives, as well as incorporated functional materials, should be also discovered. Moreover, since graphene and its derivatives can serve as both the sensing component and transducer, utilization to flexible electrode and miniaturization in size by forming free-standing structures via self-assembly would be an excellent approach for developing an implantable (flexible) and portable (lightweight) sensors as well. However, the lack of a suitable power source is a limiting factor.In addition, owing to the advantages of specific planar morphology, graphene-like 2D nanomaterials have attracted significant attention as emerging materials for electrochemical sensor approaches. Taking the advantages of diverse composition and structural effect, graphene-like 2D nanomaterials also have promoted great efforts to improve the performance of electrochemical biosensors. Similar to graphene and its derivatives, the defined synthesis method for high quality graphene-like 2D nanomaterials with controllable sizes and thickness, as well as tunable properties, and surface functionalization method is highly desirable for their practical application to electrochemical biosensor development as well. In witness of their current attention, we also endeavor that further improvement of graphene and its derivatives, as well as graphene-like 2D nanomaterial-based electrochemical biosensors, will lead to a significant advance in analytic applications for the highly effective and reliable detection of biomarker and open new avenues in biological and medical fields.