A broadband photodetector  based on such hybrid films is fabricated with a high photoresponsivity of >100 A W−1 and a fast response time of ∼100 μs. The combination of ultra-broad bandwidth, high responsivities and fast operating speeds affords new opportunities for facile and scalable fabrication of all-carbon optoelectronic devices.Graphene has emerged as a promising material for photonic applications fuelled by its superior electronic and optical properties. However, the photoresponsivity is limited by the low absorption cross-section and ultrafast recombination rates of photoexcited carriers. Here we demonstrate a photoconductive gain of ∼10 Graphene has excellent electronic properties but its photoresponsivity is limited by low absorption and the ultrafast recombination of photoexcited carriers. Here, the authors demonstrate fast, high responsivity and broadband photodetectors by combining graphene with single-wall carbon nanotubes. Combining low-dimensional nanomaterials into hybrid nanostructures is a promising avenue to obtain enhanced material properties and to achieve nanodevices operating with novel principles1−2 A W−1)1012−1 (ref. 17−12 W) due to the use of exfoliated graphene flakes 9 has been demonstratedBoth graphene and CNTs exhibit intriguing optical properties, such as broadband and tuneable light absorption, which make them promising materials for photodetectors82−1 ref. . However2−1 ref. −12 W due5 cm2 V−1 s−1 at room temperature11) in semiconducting SWNTs−3 AW−1) of single-tube photovoltaic devices greatly limits their practical use2-hybridized carbon allotropes, combined with the various strategies available for structural and chemical engineering of the interfacial electronic properties27SWNTs, on the other hand, are π-conjugated, 1D structures with nanometre diameters5, together with a high electrical bandwidth of∼104 Hz (response time∼100 μs) across visible to near-infrared range . The reported device constitutes a first implementation of large-area, quasi-2D SWNT–graphene hybrid film for optoelectronic devices and is envisaged to be important for optical communication, spectroscopy, remote sensing and high-resolution imaging applications. Equally important, we demonstrate for the first time the possibility of harvesting robust excitons widely supported in 1D systems by a 2D layered material. Our results not only open up new avenues for studying fundamental carrier transport and relaxation pathways in nanometre-scale, 1D van der Waals junctions, but also pave the way for constructing high-performance optoelectronic heterostructures by planar 1D–2D hybrid building blocks, other than the use of purely 2D layered materials.Here we demonstrate a proof-of-concept photodetector based on a planar atomically thin SWNT–graphene hybrid film. In our design, enhanced broadband light absorption is achieved in the hybrid film. Compared with pristine graphene photodetectors which exhibit only weak Schottky junction and high Auger recombination rate, the large built-in potential at the 1D-2D interface promotes effective separation of electron-hole pairs and reduces recombination of spatially isolated photocarriers. Furthermore, the trap-free interface enables a relatively fast operation rate. The devices exhibit a significant photoconductive gain of ∼102/Si substrate (see Methods). 2/Si substrate is measured to be ∼0.8 nm, indicative of single atom layer11 and S22 bands are found to be located at ∼1,800 and ∼1,000 nm with higher SWNTs loadings  as a function of the back-gate voltage (VG) under different illumination levels, where continuous negative shift of the voltage for Dirac point  is observed, confirming a photocurrent generation mechanism as depicted by 22 bandgap of the semiconducting SWNTs (∼1.2 eV), free electrons can be directly excited from the valence band to the conduction band. Photogenerated electrons in SWNTs are transferred to the graphene channel due to the built-in electric field, while the holes are trapped in the SWNTs due to the potential barrier at the interface. The conductance of the graphene channel decreases for VBG<VD where the carrier transport is hole-dominated, but increases for VBG>VD, where carrier transport is electron dominated. V) as a function of the illumination power, clearly revealing the high sensitivity of the SWNT–graphene device. ISD as a function of VG under different illumination power of 650 nm demonstrates effective tuning of the photocurrent and the photoresponsivity with the back-gate voltage, where a maximum photocurrent of >90 μA is obtained at a negative VBG around −20 V (VSD) for different optical powers at VBG=0 is clearly observed. −1, as compared with a bare graphene device∼10-2 A W−1. Since the responsivity does not show sign of saturation, higher photoresponse on the order of ∼1,000 A W−1 is expected at lower excitation power levels . The temporal photoresponse was measured at 173 K to suppress the outside interference including scattering centres from the substrate and charge-trapping surface statesResponse time is another key figure of merit for photodetectors and is also relevant in revealing the physical mechanism of the device operation. V × Cox/φphoton, where ΔV is the Dirac voltage shift, Cox is the capacitive coupling of the back-gate for 285 nm thick thermal oxide (7 × 1010 cm−2 V−1), φphoton is the photon flux. As shown in 2 V−1 s−1, respectively. This is superior to graphene sensitized with PbS QDs−9 s , thus the photoconductive gain G=τlifetime/τtransit (the ratio of the lifetime of the trapped holes over the electron transit time from source to drain) is on the order of ∼105 using a trapped carrier lifetime of ∼100 μs. Therefore the gain-bandwidth product of our SWNT–graphene device is on the order of 1 × 109 Hz (given by the product of ∼105 gain and ∼104 Hz of bandwidth), which is quantitatively similar to the PbS QD–graphene hybrid photodetectorThe EQE  was estimated using the parallel plate capacitor model−1, a typical specification for commercial photodetectors. The responsivity value is higher for shorter wavelengths than for longer ones . The responsivities for various wavelengths are summarized in ger ones , consistThe essential ingredients of our devices are the sensitivity to external electrostatic in graphene conductivity, the broadband and tuneable photon absorption in both graphene and SWNTs, and the high-speed transportation of photocarriers in the planar SWNT–graphene hybrid. To resolve the impact tube diameters and chiralities may have on the photodetection processes, we fabricated control devices using highly purified metallic tubes and 6, 5) chirality-enriched semiconducting SWNTs. Quite different photodetection mechanisms were revealed . Figure , 5 chira5, but also a fast response time of ∼100 μs and an ultra-broadband sensitivity across visible to near-infrared, covering the telecommunication band at ∼1.5 μm. Benefiting from the solution processability of SWNTs, large-scale growth and transfer of graphene, as well as compatibility with standard photolithography, our devices exhibit great potential for use in photodetection applications requiring large sensing area, high photoresponsivities, video-frame-rate processing and substrate flexibility. The results demonstrated here represent a significant step towards facile and scalable fabrication of high-performance optoelectronic devices using all-carbon hybrid nanostructures and have substantial implications for fundamental investigation of the van der Waals interactions between layered materials and in-plane quantum wires, in the 1D limit.In summary, by combining large-area CVD grown graphene with atomically thin SWNT layer, we have formed a quasi-2D all-carbon hybrid film, which exhibits strikingly enhanced photodetection capabilities superior to either graphene or SWNTs. In contrast to previous charge trap based phototransistors, such hybrid film based photodetectors exhibit not only a significant photoconductive gain of ∼10N-methyl-2-pyrrolidone). The resultant suspensions are centrifuged with 10,000 g for 1 h before the supernatant is collected for the fabrication of SWNTs thin film on SiO2/Si wafer. CVD graphene is transferred on top of the SWNTs layer using the poly(methyl methacrylate) supported procedures. Electrodes are patterned by standard photolithography. Different metal composition (Ti/Au and Pd/Au) are subsequently deposited. The graphene channel is patterned by another photolithography and oxygen plasma etching.The graphene samples were grown on copper foil by CVD method, and Raman spectroscopy combined with optical microscope characterizations point to a defect-free single-layer sample. We use single-wall CNTs (SWNTs) from a commercial supplier (Carbon solutions Inc.). The phototransistors are fabricated as follows: SWNTs suspensions are produced by tip-sonicating 1 mg nanotube soot in 10 ml NMP (−6 torr) at room temperature and the data were collected by a Keithley-4200 semiconductor parameter analyzer. The temporal photoresponse was measured at 173 K for suppressing the outside interference.For photoresponse characterization, we used 405, 532, 650, 980 and 1,550 nm laser diodes, respectively. The beam is guided through an optical fiber with a FC/PC ferrule and is subsequently incident onto the channel of the devices without focusing. The beam at the device was measured to be Gaussian-shaped with a diameter of about 300 μm at 650 nm illumination. The area of the channel is <100 × 40 μm. Therefore, when calculating the photoresponsivity, we used only the portion of the incident light intensity that overlaps with the channel area. The electrical measurements were carried out in a closed cycle cryogenic probe station under vacuum .Supplementary Figures 1-8, Supplementary Notes 1-3 and Supplementary References


Numerous agents targeting PD-L1/PD-1 check-point are in clinical development. However, the correlation between PD-L1expression and prognosis of solid tumor is still in controversial. Here, we elicit a systematic review and meta-analysis to investigate the potential value of PD-L1 in the prognostic prediction in human solid tumors.Electronic databases were searched for studies evaluating the expression of PD-L1 and overall survival (OS) of patients with solid tumors. Odds ratios (ORs) from individual studies were calculated and pooled by using a random-effect model, and heterogeneity and publication bias analyses were also performed.A total of 3107 patients with solid tumor from 28 published studies were included in the meta-analysis. The median percentage of solid tumors with PD-L1 overexpression was 52.5%. PD-L1 overexpression was associated with worse OS at both 3 years  = 1.60 to 3.70, P < 0.0001) and 5 years  of solid tumors. Among the tumor types, PD-L1 was associated with worse 3 year-OS of esophageal cancer, gastric cancer, hepatocellular carcinoma, and urothelial cancer, and 5 year-OS of esophageal cancer, gastric cancer and colorectal cancer.These results suggest that expression of PD-L1 is associated with worse survival in solid tumors. However, the correlations between PD-L1 and prognosis are variant among different tumor types. More studies are needed to investigate the clinical value of PD-L1 expression in prognostic prediction and treatment option. Co‑stimulatory and co‑inhibitory receptors play a pivotal role in T cell biology, as they determine the functional outcome of T cell receptor (TCR) signaling and immune surveillance . HoweverHuman programmed death-ligand 1 (PD-L1 or B7-H1), as a dominant ligand, plays a central role in antigen-specific T cell response mediating PD-1-dependent immune suppression. The abnormal expression of these ligands has been linked with prognosis and treatment response of multiple malignancies. For instance, overexpression of PD-L1 has been observed in different solid tumors including melanoma , 6, coloDespite the clinical development of anti-PD-L1 therapies, the prognostic value of PD-L1 overexpression across different solid tumors is still unclear. Recently, it is reported that melanoma patients with PD-L1-expressing cells at the invasive tumor margin and inside tumors are more sensitive to anti-PD-1 therapy . AnotherHere, we present a meta-analysis evaluating the prognostic value of PD-L1 overexpression in solid tumor. The purpose of this study was to estimate the correlation of PD-L1 overexpression with survival in solid tumors, thereby shed more light on the development of PD-L1/PD-1 immune check-point targeted therapy and prognostic prediction.This meta-analysis was carried out in accordance with preferred reporting items for systematic reviews and meta-analyses statement .Pubmed, Web of Science and EBSCO were searched for studies evaluating the expression of PD-L1 and survival in solid tumors from 2002 to November 2014. The search terms included “programmed death-ligand 1” or “PD-L1” or “B7-H1” or “CD274” and “neoplasms” and the results were limited to human studies of solid tumors. In addition we used the entry “programmed death-ligand 1” or “PD-L1” or “B7-H1” or “CD274” and the name of each specific solid tumor to recognize additional studies. We identified a total of 350, 346 and 249 entries, respectively. Eligibility criteria were the measurement of PD-L1 by immunohistochemistry (IHC), availability of survival data for at least 3 years, and publication in English. Studies evaluating gene expression of PD-L1 measured by polymerase chain reaction were excluded from the analyses. Citation lists of retrieved articles were manually screened to ensure sensitivity of the search strategy. Study selection was based on the association of PD-L1 and survival. Inter-reviewer agreement was assessed using Cohen’s kappa coefficient. Disagreement was resolved by consensus.The primary endpoints were overall survival (OS) at 3 and 5 years. Tumors were classified by PD-L1 expression status using cut-offs as defined by individual studies.Two authors (Pin Wu and Dang Wu) independently extracted information using predefined data abstraction forms. The following details were extracted by 2 reviewers (Pin Wu and Dang Wu): tumor type, number of patients, antibody used for the evaluation, technique used to quantify PD-L1, and cut-off to determine PD-L1 positivity. Survival data were extracted from tables or Kaplan—Meier curves for both PD-L1 negative or low (control group) and PD-L1 positive or high expression .The relative frequency of survival at 3 and 5 years between the control and experimental groups was expressed as an odds ratio (OR) and its 95% confidence interval (CI). A number of sensitivity analyses were prespecified.2 statistics. Differences between subgroups were assessed using methods as previous described by Deeks et al [Data were extracted from the primary publications and analysed using RevMan 5.3 analysis software . Estimates of ORs were weighted and pooled using the Mantel—Haenszel random effect model. Statistical heterogeneity was assessed using the Cochran’s Q and Iks et al . SensitiThe search results have been shown in We identified 28 studies using IHC techniques for the assessment of PD-L1 expression. Characteristics of included studies are shown in A description of the antibodies used in the included studies is shown in 2 = 76%), so we conducted subgroup meta-analysis to explore whether the heterogeneity is due to different cancer types.A total of 25 studies reported data for OS at 3-years. Results showed that PD-L1 overexpression was associated with worse 3-year OS of solid tumors  . There wThree studies provided 3-year OS for lung cancer, 2 studies for hepatocellular carcinoma, 2 studies for melanoma, 2 studies for oropharyngeal squamous cell carcinoma, 4 studies for urothelial cancer, 3 studies for esophageal cancer, and 3 studies for gastric cancer. In the stratified analysis by cancer types, PD-L1 overexpression was associated with worse 3-year OS of esophageal cancer  , gastric2 = 79%), so we conducted subgroup meta-analysis according to different cancer types.A total of 25 studies reported data for OS at 5-years. Similar to the 3-year OS data, PD-L1 overexpression was significantly associated with worse 5-year OS of solid tumors  . There wFour studies provided 5-year OS for lung cancer, 3 studies for hepatocellular carcinoma, 2 studies for melanoma, 2 studies for oropharyngeal squamous cell carcinoma, 3 studies for urothelial cancer, and 3 studies for esophageal cancer. PD-L1 overexpression was associated with worse 5-year OS of esophageal cancer  , gastricRemoval of studies which did not report the PD-L1 antibody clone did not influence results for 3-year or 5-year OS . However, removal of the studies that did not report the cut-off value of PD-L1 overexpression increased the association between PD-L1 and worse 3-year and 5-year OS compared with PD-L1 low expression . Exclusion of these studies did not reduce heterogeneity for 5-year OS .PD-L1 overexpression has been observed in a substantial number of solid tumors. Moreover, numerous studies have demonstrated that PD-L1 plays a key role in cancer immune escape , 41. A dResults showed that overexpression of PD-L1 was associated with worse 3-year OS for all studies analyzed except for one study of melanoma and lung cancer, respectively , 11. StuA recent study reported that epithelial-originated cancer patients with positive expression of PD-L1 on tumor tissues were associated with significantly poorer OS when compared to those with negative expression of PD-L1 . Consist+ T cells distinctly located at the invasive tumor margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy [Besides, the PD-1 expression state of tumor infiltrating lymphocytes is another key point of the PD-1/PD-L1-mediated tumor immune escape. A recent study suggests that pre-existing CD8 therapy . Moreove therapy . The eviOur analyses show that overexpression of PD-L1 in solid tumor tissues, as measured by IHC, is associated with worse prognosis in different tumor types, which suggests that the development of strategies against the PD-L1/PD-1 axis would be a promising therapeutic approach for solid tumors. Moreover, further studies are required to investigate the potential role of PD-L1 expression in solid tumors for prognostic prediction as well as PD-L1 targeted treatment decision.S1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S1 PRISMA Checklist(DOC)Click here for additional data file.


We predict the induction or suppression of magnetism in the valence shell of physisorbed and chemisorbed organic molecules on graphene occurring on the femtosecond time scale as a result of core level excitations. For physisorbed molecules, where the interaction with graphene is dominated by van der Waals forces and the system is non-magnetic in the ground state, numerical simulations based on density functional theory show that the valence electrons relax towards a spin polarized configuration upon excitation of a core-level electron. The magnetism depends on efficient electron transfer from graphene on the femtosecond time scale. On the other hand, when graphene is covalently functionalized, the system is magnetic in the ground state showing two spin dependent mid gap states localized around the adsorption site. At variance with the physisorbed case upon core-level excitation, the LUMO of the molecule and the mid gap states of graphene hybridize and the relaxed valence shell is not magnetic anymore. K points of the first Brillouin zone forming the Dirac cones9101215Graphene is a two dimensional crystalline allotrope of carbon with honeycomb lattice structure and has been extensively studied since its discovery in 2004123Pristine graphene does not display intrinsic magnetism and this limits its applications in magneto-electronics and active spintronics. This is due to the bipartite lattice structure of graphene explained by Lieb’s theorem181920212324272930et al., who showed that a rapid demagnetization is induced in Ni by using femtosecond optical pulses4041424346Time dependent effects in magnetism are an important topic of current interest. Ultrafast magnetization  has been investigated first by Beaurepaire 5H5N), 4-picoline radical (C6H6N) and pyridine radical (C5H4N), which are prototypes of different couplings with graphene. Interaction of pyridine with graphene is dominated by van der Waals forces, that of pyridine radical is mainly via chemisorption, while 4-Picoline radical is affected by both van der Waals forces and covalent bonding and represents an intermediate case between pyridine and pyridine radical. We evaluate the electronic properties for the molecules where the N atom is ionized and compare them to the ground state ones. We investigate how the electrons of the system relax around the core hole, inducing or suppressing magnetism in the valence shell depending on the type of adsorption.The motivation for this work is to understand the effect of core level excitations of adsorbed molecules on graphene, aiming at the limit where only one molecule in a diluted array of adsorbed species is core-excited. We take into account three molecules namely pyridine 484951For the excited state calculations, we use a pseudo-potential with a full core hole (FCH) created at the N 1s orbital of the molecule. We always consider a globally neutral system, where an additional electron is given to the valence shell56Eg and Em are the total energies of the isolated graphene substrate and of the gas phase molecule/radical, respectively. The adsorption energies are summarized in 5859pz orbitals of graphene as shown in π cloud remains almost parallel to graphene, at an angle of ~14° and at an average distance of 3.16 Å with respect to the substrate plane. Finally the pyridine radical, when adsorbed on graphene, forms a mostly covalent bond and orients itself perpendicular to the graphene plane as seen in aZ, defined as the height difference of the bonding carbon atom of graphene with respect to its nearest neighbours. This is visualized clearly in the acc). The results for the adsorption energies are better understood by taking pyridine radical as a reference. Picoline radical, in comparison, shows a lower value of acc and aZ, consistently with its lower reactivity. The more negative computed value of Eads is due to a stronger vdW interaction of its almost planar π cloud. In comparing pyridine molecule vs radical, we remark that in the case of covalently bonded systems on graphene, the deformation of the substrate requires a large energy cost that is lowering significantly the adsorption energy: almost 1 eV in similar systemsEads. Our effort will be to understand the effect of chemisorption and physisorption on the system magnetism in the ground and core excited states.We start by investigating the most stable configurations of pyridine, 4-picoline radical and pyridine radical adsorbed on graphene taking into account the translational as well as rotational degrees of freedom of the molecule. To check the stability of the system and quantitatively understand the energies involved during the adsorption process, we define the adsorption energy as To understand the electronic and magnetic properties of the system, we plot the total density of states (DOS) and that projected onto the molecular orbitals (MOPDOS). The latter is evaluated asδ function by a Gaussian function. The molecular states where In pyridine on graphene configuration as seen in z orbital is taken out of the π electron network2861μB magnetic moment. The molecule does not contribute directly to the formation of such states and magnetism is localized around the bonding site on graphene but on the other sublatticeBefore discussing the adsorption of 4-picoline and pyridine radicals on graphene, we recall that covalent adsorption of species bound to a C atom of graphene induces magnetism in the ground state of the system, as the respective pμB magnetic moment localized on the molecule. We remark that this magnetic configuration would occur upon 1s→LUMO excitation or, in case of photoionization, after the time needed to transfer an electron from graphene to the molecule to screen the core hole. As demonstrated by recent experiments for bipyridine molecules on grapheneWe are now in the position to study the electronic and magnetic properties for the three systems when a hole in the N 1s orbital of the molecule is created and one electron is added to the valence shell, as discussed in simulation details. The total DOS and the MOPDOS of the three molecules are shown in In the case of covalently bonded 4-picoline radical and pyridine radical, the system is magnetic in the ground state. Upon photo-ionization and relaxation of the valence shell around the core hole, the additional valence electron joins the one formerly in the midgap state and the system valence becomes spin degenerate. It remains so until the excited hole decays with a lifetime of a few femtoseconds. It is seen for the picoline and pyridine radical cases in Emin to Emax) is chosen to include either the MIDGAP-l or MIDGAP-h states. The ILDOS of the occupied MIDGAP-l and the unoccupied MIDGAP-h are plotted in π symmetry couples strongly with the facing pz orbitals of graphene which constitute the midgap states. This results in a larger energy splitting between the hybrid MIDGAP-l and MIDGAP-h states (0.55 eV) seen in the MOPDOS of μB magnetic moment, eventually occupying singly both MIDGAP-l and MIDGAP-h with the same spin. Such a configuration is less stable than the non-magnetic case by 0.36 eV. Relaxation towards the spin-compensated solution could occur by resonant transfer of two electrons with majority and minority spin to and from the surrounding graphene, respectively, provided this is faster than the core-hole lifetime.where the energy range , whose integral amounts to the additional valence electron. Let us consider first the results for physisorbed pyridine shown in ρ in terms of projection onto atomic orbitals according to Löwdin population analysis65ρ and noticing that larger charge lobes on graphene are depicted in ρ on the atoms of the molecule amounts to 63% for the 4-picoline radical and 59% for the pyridine radical cases.A further distinction between the different adsorption systems can be inferred by calculating the screening charge which is defined as Finally we remark that we deal with a local phenomenon independent of possible long range magnetic order. Given the limited extent of the core-level excitation, experiments to detect the local spin balance are conceivable when in the presence of the core hole, electrons are transferred from the substrate to the molecular LUMO levelWe have studied the magnetic properties of ground state and core-excited organic molecules on graphene from first principles. It is found that the adsorption mechanism plays an important role in inducing or suppressing magnetism in the valence shell of the system within the core hole lifetime. The physisorbed system where the interaction is dominated by van der Waals forces and initially non-magnetic in the ground state becomes magnetic when a core electron is excited. The system is magnetic until the core electron de-excites via one of the several electronic decay channels. An opposite behaviour can be appreciated when molecules are covalently bonded to graphene and the substrate is hence magnetic. Here magnetism is suppressed upon core electron excitation. The LUMO of the molecule hybridizes with the mid gap states of graphene forming spin-compensated bonding and anti bonding combinations. The valence shell remains non magnetic until the core electron de-excites. Since the time scale of the magnetism we are dealing with is in the order of a few femtoseconds and considering the recent advances in femtomagnetism and ultrafast measurements for adsorbed molecules, experiments complementing our work could soon be available.How to cite this article: Ravikumar, A. et al. Femtomagnetism in graphene induced by core level excitation of organic adsorbates. Sci. Rep.6, 24603; doi: 10.1038/srep24603 (2016).


Graphene exhibits unique 2-D structural, chemical, and electronic properties that lead to its many potential applications. In order to expand the scope of its usage, graphene hybrids which combine the synergetic properties of graphene along with metals/metal oxides and other nanostructured materials have been synthesized and are a widely emerging field of research. This review presents an overview of the recent progress made in the field of graphene hybrid architectures with a focus on the synthesis of graphene-carbon nanotube (G-CNT), graphene-semiconductor nanomaterial (G-SNM), and graphene-metal nanomaterial (G-MNM) hybrids. It attempts to identify the bottlenecks involved and outlines future directions for development and comprehensively summarizes their applications in the field of sensing and sensitized solar cells. Graphene exhibits extraordinary mechanical, thermal, and electronic properties such as high specific surface area per unit volume, high chemical stability, excellent thermal conductivity (up to 5000 W m−1 K−1)  , whose properties emerge in the axial direction, can be functionalized onto the surface of graphene, combining the properties of the two carbon allotropes in all directions while allowing for an increased active surface area and faster electron transfer kinetics. Similarly, combining metal/metal oxide nanoparticles (NPs) with graphene overcomes NP shortcomings of low stability and tendency to aggregate resulting in highly stable electrochemical sensing platforms for anchoring with good dispersion, excellent conductivity and catalytic properties of NPs. This transformation of 2D graphene into three-dimensional (3D) architectures expands the functionality of nanomaterials and serves as novel hybrid electrode material for applications in electronics , graphene-semiconductor nanomaterial (G-SNM), and graphene-metal nanomaterials (G-MNM) hybrid nanostructures based on graphene as a multifunctional platform. Nanoscale architecture is key for the performance of these novel materials, aspects such as size, geometry, chemistry of the building blocks, relative orientation of crystals, as well as the limitations and fabrication methods must be considered during development of devices that make use of graphene hybrids. Given their wide scope, we have briefly reviewed the applications of these graphene hybrids primarily in two of the most advanced fields, namely sensing and energy harvesting. This review shall enable the reader to realize the versatility graphene hybrid materials offer by virtue of their synergistic properties. Wherever applicable, the limitations of the present approaches and future research directions have been highlighted.assembly method synthesizes graphene and CNTs, SNMs, or MNMs separately and then assembles them together. The in situ method grows CNTs, SNMs, or MNPs directly on the graphene structures.Hybridization of graphene variants such as epitaxial graphene, graphene oxide (GO) or chemical vapor deposition (CVD) graphene, with CNTs, semiconducting nanomaterials (SNMs), and metal nanomaterials (MNM) can be done by two fundamentally different approaches. The This is a widely used method in graphene hybrid synthesis involving either self- or chemical assembly. Self-assembly is a technique based on the spontaneous organization that the components  undergo when encountered in a liquid media through simple physical dispersion. Chemical assembly uses a chemical linker or electrostatic interactions to assemble the components in a layer-by-layer-method to form lamellar architecture.2 structure to form a high surface area hybrid structure. Electrostatic or covalent assembly is carried out using highly oxygenated functional groups on GO or by introducing complementary functional groups in the sp2 lattice of CNTs and graphene through different chemistries.Graphene and CNTs interact via van der Waals forces or π –π interaction through their aromatic spGO prepared by Hummer's method has many oxygen containing functional groups and is therefore readily soluble in water. CNTs, however, tend to agglomerate in while suspended in water and surfactants are needed for uniform dispersion. The high dispersibility of GO in water and its π –π interaction with CNTs facilitates the dispersion of CNTs without use of surfactant. Additionally, the CNTs help prevent the restacking of GO sheet  with doctor-blade. The dried electrode was then treated with hydrazine vapor and annealed to completely reduce the GO.SNMs and graphene can be mixed in a liquid through mechanical stirring, bubbling, or sonication and induced into assembly by different interactions between the surfaces. GO is preferably used in aqueous reaction due to its hydrophilic nature compared to other forms of graphene. Yang et al.  preparedIntermolecular non-covalent forces, such as hydrophobic–hydrophobic/π –π interactions, between graphene and molecules with similar structure, like pyrene, can be used to graft semiconductor nanoparticles on graphene in suspension. Katsukis et al.  employed2 has been used to mediate the photochemical reduction of GO with simultaneous assembly of TiO2 NPs onto the surface of rGO, in a single step method that is environmentally friendly  were grown between the sheets using thermal pyrolysis of iron containing precursor to from a 3D pillared structure. 3D pillared structures made of CNTs in between parallel graphene sheets possess desirable out-of plane electronic transport and superior mechanical properties. They retain the intrinsic properties of the individual components and have improved surface area for applications such as immobilization of materials and electrolyte exchange through diffusion  and metal substrate (graphene growth) interaction, it may be necessary to use a two-step growth method. Specifically in the case of iron catalyst on copper foil it has been reported that CNT growth was difficult due to hindrance of the active catalyst surface by possible formation of Fe/Cu alloy , CVD, metal-organic vapor phase epitaxy (MOVPE), and atomic layer deposition (ALD) for the growth of SNM/graphene hybrids.CVD is one of the most common methods for ZnO growth on graphene, given the relatively low melting and boiling point temperature of Zn  by flowing oxygen and an organic Zn precursor in a gas phase reactor. The gas molecules break up when in contact with graphene surface and ZnO is immediately adsorbed onto the surface. This method results in highly crystalline material without defects such as stacking faults or dislocations .Yan et al.  synthesiin situ Cu2S/rGO hybrid 2, H2O, Na2S, and H2O, providing the ions for the CdS. The described stacking was repeated several times. Finally, the GO was reduced with hydrazine evaporation and annealed at 400°C  is a technique largely used for QD synthesis in variety of substrates. It has been combined with layer-by-layer to fabricate a stacked triple-composite with titania nanosheets (TNS), rGO, and QD (CdS). After one cycle of layer-by-layer stacking of TNS and GO, the material was subjected to the SILAR cycle, a successive immersion in solutions of Cd and produces AuNP on graphene  from redox center to the electrode.Enzymatic glucose biosensors primarily use glucose oxidase (GOx) which is stable and highly specific for glucose. Glucose oxidase catalyzes the oxidation of the glucose in the presence of oxygen to produce gluconolactone and hydrogen peroxide. Flavin adenine nucleotide (FAD) is the active center of the enzyme responsible for the redox reaction. First generation glucose biosensors electrochemically detect HDET is difficult to achieve with GOx enzyme on bare electrodes such as a glassy carbon electrode, as FAD is deeply embedded in the structure. Graphene based hybrids provide an efficient and highly conductive matrix for enzyme immobilization and faster electron transfer in achieving the DET for GOx without use of any mediator thus finding application in glucose sensing. Though exact mechanism by which theses hybrids achieve DET is unknown, proximity of highly conductive graphene and its 3D hybrids with superior electrochemical properties bring DET into reality. DET of GOx is characterized by the presence of FAD redox peaks in cyclic voltammetry with formal potential close to GOx standard electrode potential, i.e., between −0.4 and −0.5  (PLL) polymer as a linker. Cadmium sulfide (CdS) in the form of nanocrystals, hollow nanospheres, and nanoparticles have been successfully shown to achieve DET for the redox enzyme /graphene together yields a hybrid possessing electrochemical properties of metal and graphene and easy processibility of polymer. PANI provides compatible supporting matrices for both enzyme and AuNP   into electrical/optical signals for sensing. The large surface area and adsorptivity of SNM increases the electric response of sensors while graphene enhances adsorption of biomolecules and increases signal-to-noise ratio.2, wherein the resistance changes with varying H2 concentrations  , Surface-enhanced Raman Scattering (SERS), and Surface Plasmon resonance (SPR) phenomenon.Table Meng et al.  recently3 and NO2 has been reported with Ag/RGO composite with the lowest detection limit of 15 and 0.5 ppm by Phan and Chung , biomolecules (BSSC), and quantum dots (QSSC), deposited on a conductive transparent surface that conducts photogenerated electrons from the semiconductor into the external circuit.Sensitized solar cells (SSCs) have attracted considerable interest since Grätzel's group introduced nanostructured TiOGraphene in SSC has been applied in both photoanode and counter electrode, playing distinct roles. First, given its extremely high mobility, it can be used as transparent conductive film in the photoanode. As conductive film it would substitute currently used metal oxides, such as FTO and ITO, as it overcomes the disadvantages of the metal oxides, such as cost, sustainability, chemical and mechanical resistance, and higher transmittance in the near-infrared range , rGO and CdS QD has also confirmed the role of graphene in providing additional paths for electrons to be collected in the photoanode and a faster hole transport to the electrolyte, greatly suppressing electron-hole recombination (Yang et al., Son et al.  demonstr2/FTO counter electrode was 6.18%, only slightly lower than the 6.52% of a Pt counter electrode. Graphene's large surface area readily captures the electrons from redox couples in the electrolyte thereby easily reducing them. So, similar to its role as bridge as in the photoanode, the graphene facilitates electron transmission across the counter electrode/FTO interface. However, graphene absorbs light, therefore less light is reflected from the counter electrode and light harvesting efficiency is reduced in comparison to Pt. rGO/Cu2S on FTO has also been used as counter electrode for CdS/CdSe/ZnS QSSC by Radich et al. (2S exhibits higher photocatalytic activity toward polysulfide electrolyte reduction than Pt, and rGO platform stabilizes the nanoparticles, its large surface area promotes good dispersion and provides high number of reactive sites, while the good mobility serves to rapidly shuttle electrons to the Cu2S catalyst sites. The fill factor of the hybrid was increased in 75% in comparison to Pt, confirming the more efficient shuttling of electrons, resulting in one of the highest power conversion efficiency reported for liquid junction QDSSC.Graphene/SNMs also have been proven advantageous when used as counter electrode. Pt is a well-known counter electrode material due to its high electrocatalytic activity toward the most common electrolyte in SSC, iodide/triiodide. However, due to its scarcity and cost, finding inexpensive substitutes is crucial. A combination of highly electrocatalytic chalcogenide semiconductors and graphene on FTO have proven to be feasible substitutes for Pt (Liu et al., h et al.  and Santh et al.  with imp3−.Graphene-CNT hybrid materials have recently been studied for their use mainly as a counter electrode in SSC, but also as part of the photoanode and the electrolyte. Guang et al.  incorpor−3. The performance of Pt as counter electrode is hard to overlook, however, its high cost is a motivation to search for substitutes. Different architectures of the hybrid have been reported for this application that don't affect the performance of the cell significantly. Tripathi et al. (The main hybrid under this category is graphene-Pt, since Pt is the standard electrocatalyst for the reduction of Ii et al.  studied i et al.  reportedi et al.  has repoWhether as a transducer in mediatorless glucose biosensors, a photoactive material, electronic transfer aid, or charge collector platform, graphene's use has been steadily increasing and impacting modern day electronics. Hybridization of graphene with carbon nanomaterials and semiconductors can be performed by innumerable methods that continue to be discovered. Despite its excellent properties, graphene still has a long way to go before it can replace silicon or tin oxide films, largely because it's reproducibility and large scale production with process control of layer number still remain a challenge. When designing graphene hybrid materials great attention must be paid toward optimizing the intrinsic properties of the components simultaneously with the interface structure and mechanisms of electronic coupling, some of which are still unknown. As we have selectively reviewed the recent advances of graphene-CNT, graphene-SNM, and graphene-MNM hybrids with focus on sensing and energy conversion, it can be easily realized that this trend of using graphene hybrids with their multifunctionalities and multimodalities will continue to proliferate in fields of flexible electronics, medical diagnostics, chemical sensing, solar cells, and many other transduction devices.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The interconnected CFs are used as both current collector and electrode materials for flexible supercapacitors, in which the in-situ exfoliated graphene act as active materials and conductive “binders”. The in-situ electrochemical intercalation technique ensures the low contact resistance between electrode (graphene) and current collector (carbon cloth) with enhanced conductivity. The as-prepared electrode materials show significantly improved performance for flexible supercapacitors.Flexible energy storage devices are highly demanded for various applications. Carbon cloth (CC) woven by carbon fibers (CFs) is typically used as electrode or current collector for flexible devices. The low surface area of CC and the presence of big gaps (ca. micro-size) between individual CFs lead to poor performance. Herein, we interconnect individual CFs through the  A fast-growing market for electronic devices and the development of hybrid electric vehicles result in an ever increasing demand for environmentally friendly and low-cost energy devices1234578et al.et al.11With rapidly growing demand for personal electronics with small, thin, light-weight, flexible, and even roll-up characteristics, more and more attentions have been devoted to the flexible energy storage systems including flexible supercapacitors for these electronic devices111213ca. micro-size) between individual carbon fibers are generated, as observed by the scanning electron microscopy (SEM) images . During the production of carbon cloth, inevitably, big gaps  images  which wo4 as reference electrode, and tetramethylammonium perchlorate (TMAClO4) as electrolyte. We performed the cyclic voltammetry (CV) scanning to define a proper potential for the chronoamperometric (CA) mode to start the electrochemical cation intercalation process. As shown by the CV curves in 17in-situ exfoliated graphene, as shown in The electrochemical cation intercalation of carbon cloth was conducted by using a three-electrode system with carbon cloth as working electrode, Pt mesh as counter electrode, Ag/AgClO0 axis, indicating the microporous nature of of carbon fibers in CC3/g, much higher than that of CC (0.011 cm3/g). After the electrochemical cation intercalation, Ex-CC exhibited much higher surface area (68.5 m2/g) than CC without intercalation (11.5 m2/g). The enhancement of the surface area by the in-situ interconnected graphene could be clearly found.Based on the SEM observation, graphene was successfully exfoliated and acted as interlinkers to interconnect individual carbon fibers. It is well-known that graphene always has high surface area, therefore, it is expected that the interconnected carbon fibers by graphene, that is, Ex-CC would show much higher surface area than pristine CC. We performed the Brunauer Emmett Teller (BET) testing for Ex-CC as well as CC for comparison. D band and G band were located around 1330 and 1580 cm−1, respectively. It has been found that G band arises from the bonding stretching of sp2-bonded C-C pairs, while the D band is associated with the sp3 defect sites. In the Raman spectra of carbon-based materials, the ratio of ID/IG was usually used as an indicator of the defects level. It can be seen from D/IG ratio than pristine CC. For Ex-CC, graphite in carbon fibers was exfoliated to graphene, resulting in more exposure of edge defects and thus higher D band intensity in the Raman spectrum.The electronic properties of Ex-CC and CC were investigated by Raman spectra. Raman spectroscopy is an excellent tool for investigating the electronic structure and defect concentration in graphene2021222 and sp3 C1s, respectively3 C of Ex-CC increased relative to the pristine CC, indicating more edge defects exposed after exfoliation, in consistent with the observation of the Raman spectra as discussed above. It should be pointed out that no obvious oxygen-containing species were observed for Ex-CC, indicating the electrochemical cation intercalation is a non-oxidative route, which preserved the highly conductive properties of graphene.In order to monitor the change of the C bond configuration, fine-scan C1s spectra were collected from both CC and Ex-CC, as shown in 2SO4 solution as the electrolyte. For comparison, pristine CCs were also assembled to a symmetric flexible supercapacitor. The area of the devices is 2 × 2 cm2. CV measurements were first carried out to observe the electrochemical behaviour of Ex-CC and CC-based flexible supercapacitors. in-situ exfoliated graphene would enhance the conductivity of the composites for use as electrode materials. From the CV curves, it could be observed that Ex-CC showed much higher current than CC, which could be attributed to the unique structure of the interconnected carbon fibers through the in-situ exfoliated graphene.Based on the above physical and chemical characterizations, it is expected that Ex-CC would have attractive electrochemical performance in supercapacitors. Since the Ex-CC with high surface area originates from CC and preserves the well-defined cloth structure with good mechanical strength, Ex-CC could be an excellent candidate as an advanced binder-free electrode for flexible supercapacitors. The symmetric flexible supercapacitors were constructed using two Ex-CC samples as both positive and negative electrodes, Whatman filter membrane as the separator, and 1.0 M HIR drop of the Ex-CC is much smaller than CC. The IR drop is caused by the equivalent series resistance (ESR), which includes electrode resistance and electrolyte resistance. The smaller IR drop on Ex-CC is attributed to the existence of various pore structure and high conductivity of the in-situ exfoliated graphene. The specific capacitance in this work was calculated from the CD curves. In addition, the in-situ exfoliated graphene filled the gaps between individual carbon fibers in Ex-CC samples; therefore, it is interesting to investigate the contribution of the in-situ exfoliated graphene to the area-normalized capacitance. So, in this work, the specific capacitances were described with “mF cm−2”. According to the calculation, the area-normalized capacitance of Ex-CC at the discharge current of 3 mA is 64.5 mF cm−2, much high than that of CC (17.1 mF cm−2). The higher area-normalized capacitance of Ex-CC may be attributed to the presence of the in-situ exfoliated graphene with high surface area and high conductivity. Furthermore, we investigated the durability of the Ex-CC electrode using continuous charge/discharge cycles at a constant current load of 5 mA. In order to further investigate the performance of the two electrodes, galvanostatic charge-discharge (CD) experiments were carried out with the voltage windows the same as for the above CV analysis. As shown in the CD curves , the disFinally, we examined the electrochemical performance of the as-fabricated flexible supercapacitor based on Ex-CC as the electrode materials under bending conditions. Based on the above analysis, it could be found the individual carbon fiber in the carbon cloth could be efficiently interconnected by the electrochemically exfoliated graphene. The morphology characterizations demonstrate the ideal structure for the potential applications in supercapacitor due to more exposed active sites for charge storage. On the other hand, the enhanced capacitance as demonstrated by the electrochemical testing may also be attributed to the increased conductivity of the composite. The exfoliated graphene could significantly decrease the contact resistance between individual carbon fibers by linking each together.in-situ electrochemical exfoliation method. The electrochemical exfoliation leads to generation of graphene without de-attachment from carbon fiber under mild exfoliation conditions and preserves the high conductivity of graphene without the formation of oxygen-containing species. The exfoliated graphene, which remains in the matrix of carobn fibers, acted as conductive “binders” to enhance the conductivity and to increase the surface area of the composites2627In summary, we successfully interconnected carbon fibers of CC with graphene through the 4 as reference electrode in 0.1 M TMAClO4 in NMP as electrolyte. First of all, Voltammetry was performed as a scan rate of 20 mV/s. The potentials observed in the cyclic voltammetry (CV) were used to define the potential set in the chronoamperometric mode to control the mild intercalation process. Subsequently, −2.5 V was chosen for the chronoamperometric mode to realize the mild electrochemical exfoliation for 10000 s. Following the electrochemical exfoliation, the as-obtained Ex-CC was washed with acetone thoroughly.The electrochemical exfoliation of carbon cloth was conducted in a three-electrode system with carbon cloth as working electrode, Pt mesh as counter electrode and Ag/AgClO2 were used as the positive electrode and negative electrode, respectively. Whatman membrane was used as the separator and 1 M H2SO4 in aqueous was used as electrolyte. For comparison, CC based supercapacitors were also assembled in the similar way.To construct Ex-CC based flexible supercapacitor device, two pieces of Ex-CC electrodes with the size of 2 × 2 cm2).Cyclic voltammetry and galvanostatic charge/discharge tests of assembled two-electrode supercapacitors were carried out using an Autolab potentiostat/galvanostat. CV measurements were conducted in the applied voltage window of 0–1 V. Galvanostatic charge/discharge tests were operated under a constant charge/discharge current of 3 mA within an applied voltage window range from 0 to 1 V. The specific capacitance was calculated from the galvanostatic charge/discharge curves normalized by the surface area of the devices .


Proton transfer across single-layer graphene proceeds with large computed energy barriers and is therefore thought to be unfavourable at room temperature unless nanoscale holes or dopants are introduced, or a potential bias is applied. Here we subject single-layer graphene supported on fused silica to cycles of high and low pH, and show that protons transfer reversibly from the aqueous phase through the graphene to the other side where they undergo acid–base chemistry with the silica hydroxyl groups. After ruling out diffusion through macroscopic pinholes, the protons are found to transfer through rare, naturally occurring atomic defects. Computer simulations reveal low energy barriers of 0.61–0.75 eV for aqueous proton transfer across hydroxyl-terminated atomic defects that participate in a Grotthuss-type relay, while pyrylium-like ether terminations shut down proton exchange. Unfavourable energy barriers to helium and hydrogen transfer indicate the process is selective for aqueous protons. Proton transfer across graphene is associated with large computed energy barriers and is thought to be generally unfavourable. Here, the authors observe aqueous proton transfer through graphene subjected to pH cycling, suggesting that it is due to transfer through rare, naturally occurring atomic defects. As shown in 141519a,eff values of 3.5(1) and 8.3(2), which fall within the reported literature values  images of graphene single layers deposited on fused silica windows show a low density of macroscopic pinholes and that the graphene is free of cracks or folds . Two-dims−1 refs , 38, 39.− groups . This re−5 cm2 s−1, or just half of that of bulk water, once protons arriving through any opening within the graphene sheet interact with the hydroxylated portion of the surface that is located behind the reaction front. To conservatively assess an upper bound limit for our estimations, we calculated the proton mean-square displacement using a D-value of 1 × 10−6 cm2 s−1. The probability of placing our laser beam within the propagating reaction front emanating from a given macroscopic pinhole was then estimated to be 4% and 21% for 1 and 10 s SHG jump times, respectively  was then used to search for atomic defects using annular dark field (ADF) STEM imaging at 60 kV (see Methods). The majority of the images show perfect six-fold symmetry in the position of the carbon atoms and vast areas that lack grain boundaries and atomic, or vacancy, defects . Neverth44To elucidate the mechanisms for proton transfer, we discuss findings from density functional theory (DFT) calculations  and Reax50We find that the main restriction for aqueous proton transfer through pristine, defect-free graphene is the energy required to push the proton through the center of an aromatic ring in the hydrophobic graphene layer as shown in The basal planes of pristine graphene can, and do, contain rare atomic-scale defect sites comprised of carbon atom vacancies, as shown in et al.)All of the defect terminations considered are energetically favourable as compared with the bare quad-vacancy system . The rem2 transfer requires barriers exceeding 1.9 eV  to fill ~1 cm2 with a single layer. Following annealing in a flow of 4% H2 in Ar for 30 min at 300 °C, vibrational sum-frequency generation spectra showed no evidence for CH stretchesWe used graphene having a grain size of ~100 μm ref.  grown on54SEM images were collected from the center of the graphene film. Graphene on an optical window was imaged using a Hitachi S-4800 scanning electron microscope (SEM) operating at 2 kV with a probing current of 10 μA and an Everhart–Thornley detector. Copper tape was used to reduce charging effects. Individual images were taken at × 1,200 magnification with 1,280 × 960 resolution. An array of 5 × 5 images  was stitched together using Adobe Illustrator. Automatic brightness and contrast adjustment on each frame was carried out using the ‘auto adjust’ feature in Preview . No other postedit feature or change was applied.−5 torr) for 8 h to remove surface contamination. Following heating in vacuum, the specimen was immediately transferred to the UltraSTEM for ADF STEM imaging. The surface of the graphene still retains residual PMMA that was used in the transfer processes to the transmission electron microscopy grid as shown in To confirm the single-layer nature of graphene synthesized using the CVD method2 and NaCl . The concentration of NaCl was confirmed using a conductivity meter . Solution pH was adjusted with minimum amounts of dilute solutions of ~1 M NaOH  and HCl (EMD ACS grade). The pH-jump experiments were carried out using a fused silica hemisphere  pressed against either a fused silica window  or a CVD-prepared graphene film transferred onto a silica window in an experimental setup previously reported13The aqueous solutions were prepared with Millipore water, prepared the day before an experiment and left open to air overnight to equilibrate with atmospheric CO−1 flow using variable flow peristaltic pumps as previously reported13As shown in 134 μJ cm−2 per pulse with a 30 μm focal spot, which is well below the damage threshold of graphene as previously reported1313A detailed description of our SHG setup has been described previously606162Ab Initio Simulation Package64x and y dimensions. A 15 Å gap was inserted between the graphene layer perpendicular to the surface. The gap was subsequently filled with enough water molecules to match the overall density of water at 1.0 × 103 kg m−3. The initial simulations were carried out with water on both sides of the graphene layer. The lower SiO2 substrate was initially simplified by using additional water. Subsequent calculations were carried out with more realistic slabs comprised of water/graphene/water/SiO2 substrates. The reaction rates and mechanisms of proton transfer through the graphene were described in the framework of transition state theory and within the harmonic approximation, which is robust for systems of high densities.First-principles periodic DFT calculations were carried out to determine the lowest energy interfacial water/graphene, water/graphene/water/silica structures and the activation barriers for proton diffusion through these interfaces using the Vienna −5 eV. All of the atoms were allowed to relax in the geometry optimizations until the forces on each atom were <0.03 eV Å−1. Spin polarization was examined for all of the systems explored and applied when needed. Transition states were isolated using the nudged elastic band method44All of the calculations were carried out within the generalized gradient approximation using Perdew–Burke–Ernzerhof functionalab initio MD to validate predictions of force field in describing water/graphene systems .Supplementary Figures 1-26, Supplementary Tables 1-3, Supplementary Notes 1-13 and Supplementary References


In this way, it is possible to simultaneously obtain a regular, non-covalent paving as well as supramolecular functionalization of graphene, thus opening interesting perspectives for nanoscience applications.Two-dimensional (2D), supramolecular self-assembly at surfaces is now well-mastered with several existing examples. However, one remaining challenge to enable future applications in nanoscience is to provide potential functionalities to the physisorbed adlayer. This work reviews a recently developed strategy that addresses this key issue by taking advantage of a new concept, Janus tecton materials. This is a versatile, molecular platform based on the design of three-dimensional (3D) building blocks consisting of two faces linked by a cyclophane-type pillar. One face is designed to steer 2D self-assembly onto C(sp Graphene is of significant interest for next generation electronics  particul2 hybridized carbon atoms into sp3 hybridized. As a consequence, this disruption of the C-sp2 leads to the alteration of the characteristic electronic properties of graphene. For this reason, the non-covalent functionalization of graphene is expected to be more interesting, offering the opportunity to attach any functionality while simultaneously maintaining the integrity of the sp2-hybridized carbon network  [3 grafting strongly affects the delocalization of electrons within the graphene layer, making it incompatible for applications such as sensors [This can be achieved either by covalent or non-covalent approaches . In the perties) . This as sensors . Finally sensors .However, the controlled positioning and organization of functional molecules into self-assembled monolayers at surfaces represent a major challenge for potential applications in various fields of nanotechnology –10. Amon2-hybridized carbon supports (such as HOPG and graphene) with periodic arrays of functional 3D building blocks, known as Janus tectons [2)-based substrates, and (ii) independently exposing off-plane functionalities with controlled lateral order on demand.In this context, we recently developed a successful new strategy taking place at the liquid–solid interface at room temperature (RT) for the precise nanometer-scale 2D decoration of flat sp tectons . Here, w2)-based substrates was proposed [2)-based substrates and allowed for the first realization of a predetermined. “on demand” series of 0D, 1D or 2D topologies, based on a single rigid molecular core on HOPG. These achievements are based on the rational design of a novel functional molecular group, which turns into a non-covalent clip-like bond activated by graphite   have been designed, synthesized, and self-assembled on HOPG  at the liquid–solid interface. As expected, they form non-covalent, surface self-assembled dimers, supramolecular linear polymers, and 2D networks. The versatility of the design was then demonstrated by synthesizing bifunctional molecules bearing two functional “clips” that end-cap a central moiety consisting of, for example, a benzene ring (IV) . As showThese results demonstrate that we are now able to control the supramolecular self-assembly on HOPG. First, a new tool acting as a functional moiety for surface-specific supramolecular bonding has been designed by combining and controlling molecule–substrate epitaxial adsorption and intermolecular packing interactions. Second, the “molecular clip” concept validity was demonstrated through the good match between the various expected and experimental topologies resulting from the supramolecular self-assembly at the liquid–HOPG interface of designed building blocks.2)-based substrates. In this context, we proposed for the first time a novel and highly versatile concept, the Janus-like 3D tecton concept. This building block consists of two different faces  and a spacer linking them. Face A was designed to act as a pedestal capable of steering a 2D self-assembly onto the substrate, while B is a functional entity . The spacer acts as a pillar ensuring the decoupling of the B face from the substrate. Moreover, if the Janus tecton is laying on the substrate via the A face, the formation of a well-organized, in-plane monolayer covering the surface is expected as well as the steered positioning of the B face out of the plane. This concept was validated by designing and synthesizing the 3D tecton reported in In the second stage, the design of 3D building blocks was pursued . This stx,y,z) of a chromophore above a substrate. Moreover, due to its substantial, inherent tunability, this strategy opens up a promising novel route toward functional molecular nanostructures and new perspectives towards active surfaces and interfaces on C(sp2)-based substrates.With these last results, it was demonstrated that (i) the multi-story molecules stack perpendicular to the substrate paving HOPG with long-range ordering, and (ii) the “floor” does not disturb the self-assembly in supramolecular, linear polymeric chains, even at large scales. Thus, this approach appears to be a breakthrough given the ability to control the 3-axis positioning , exposing as an upper face different functional moieties such as triazine-4,5-diamine, 2,6-bis(2-pyridyl)pyridine and ferrocene units.a = 3.84 nm, b = 2.08 nm and α = 64°) regardless of the building block. These values are compatible with those of the lattice formed by the neat ground floor [a∙b∙sinα = 7.18 nm2) with the calculated cross-sectional areas occupied by each upper unit  can partially explain these features. All of the upper units are size-compatible with the huge footprint value.The self-assembly properties of the JAPs and JAs were investigated by STM at the liquid–HOPG interface, at room temperature . First, nd floor . Then, ind floor . Both thFinally, the self-assembly of the Janus tectons onto a graphene monolayer, grown by chemical vapor deposition onto a polycrystalline foil, was investigated. As evidenced by a typical STM image  recorded2-carbon-based substrates (including graphene) has been investigated. In contrast to other studies performed by evaporating low molecular weight molecules under UHV conditions, in our approach, the self-assembly is achieved at the liquid–solid interface, additionally allowing the physisorption of higher molecular weight molecules.These results demonstrate that for the first time a general platform for the non-covalent functionalization of flat sp2)-based substrates, the Janus tecton concept offers a versatile platform towards the non-covalent functionalization of graphene. The reported strategy is expected to be applicable for the generation of self-assembly systems exhibiting on demand functionalization, expanding the application possibilities of this functionalization method. Moreover, working at the liquid–solid interface makes this strategy easy to implement and should also provide the opportunity to control the self-assembly by tuning the molecule–solvent and solvent–substrate interactions. Finally, the successful self-assembly on graphene, together with the possibility to transfer the graphene monolayer onto various substrates, should open up new opportunities in nanoscience.Using the molecular clip concept as a tool for supramolecular bonding on C(sp


LINE-1 (L1) retrotransposons represent approximately one sixth of the human genome, but only the human-specific L1HS-Ta subfamily acts as an endogenous mutagen in modern humans, reshaping both somatic and germline genomes. Due to their high levels of sequence identity and the existence of many polymorphic insertions absent from the reference genome, the transcriptional activation of individual genomic L1HS-Ta copies remains poorly understood. Here we comprehensively mapped fixed and polymorphic L1HS-Ta copies in 12 commonly-used somatic cell lines, and identified transcriptional and epigenetic signatures allowing the unambiguous identification of active L1HS-Ta copies in their genomic context. Strikingly, only a very restricted subset of L1HS-Ta loci - some being polymorphic among individuals - significantly contributes to the bulk of L1 expression, and these loci are differentially regulated among distinct cell lines. Thus, our data support a local model of L1 transcriptional activation in somatic cells, governed by individual-, locus-, and cell-type-specific determinants.DOI:http://dx.doi.org/10.7554/eLife.13926.001 Retrotransposons, also known as jumping genes, have invaded the genomes of most living organisms. These fragments of DNA have the ability to move or copy themselves from one location of a chromosome to another. Depending on where they insert themselves, retrotransposons can modify the sequence of nearby genes, which can alter or even abolish their activity. Although these genetic modifications have contributed significantly to the evolution of different species, retrotransposons can also have detrimental effects; for example, by causing new cases of genetic diseases.Adult human cells have a number of mechanisms that work to keep the activity of retrotransposons at a very low level. However, in many types of cancers retrotransposons escape these defense mechanisms and ‘jump’ actively. This is thought to contribute to the development and spread of cancerous tumors.To understand how jumping genes are mobilized, a fundamental question must be answered: is the high jumping gene activity observed in some cell types a result of activating many copies of the retrotransposons, or only a few of them? This question has been difficult to address because there are more than one hundred copies of retrotransposons that could potentially move in humans, many of which have not even been referenced in the human genome map. Furthermore, each copy is almost identical to another one, making it difficult to discriminate between them.Philippe et al. have now developed an approach that can map where individual retrotransposons are located in the genome of normal and cancerous cells and measure how active these jumping genes are. This revealed that only a very restricted number of them are active in any given cell type. Moreover, different subsets of jumping genes are active in different cell types, and their locations in the genome often do not overlap.Thus, whether jumping genes are activated depends on the cell type and their position in the genome. These results are in contrast to the prevalent view that retrotransposons are activated in a more widespread manner across the genome, at least in cancerous cells. Overall, Philippe et al.’s findings pave the way towards characterizing the chromosome regions in which retrotransposons are frequently activated and understanding how they contribute to cancer and other diseases.DOI:http://dx.doi.org/10.7554/eLife.13926.002 At least half of our DNA is derived from repeated and dispersed sequences called retrotransposons, a class of mobile genetic elements which proliferate via an RNA-mediated copy-and-paste mechanism termed retrotransposition  L1HS-Ta subfamily and with older copies of retrotransposition-incompetent subfamilies. Theoretically, the high L1 activity observed in particular cell types could result from global unleashing of most L1HS-Ta copies. Alternatively, it could derive from a few deregulated L1HS-Ta instances. To resolve these competing models, we mapped the location of each L1HS-Ta element dispersed in the genome of a panel of normal and transformed human cells, identified a genomic signature for the transcriptionally active copies and investigated the contribution of each of them to the bulk of L1HS-Ta transcripts. We found that individual L1 instances exhibit both locus- and cell-type-specific activation, implying that L1 mutagenic activity originates from 'hot L1' inserted in permissive loci and suggesting an unforeseen new layer of cell-type specific regulation to control endogenous retrotransposons.Human L1-derived RNA-transcripts and proteins, required for L1 retrotransposition, are detected in embryonic stem cells, in embryonal carcinoma cells, and other transformed cells or tumors, as well as in neuronal progenitor cells, but not in most primary cells, such as fibroblasts . To studAs a first estimate of L1 activity, we quantified and compared the endogenous levels of the L1-encoded ORF1p protein in distinct cell-lines. We detected ORF1p expression in whole cell extracts of half of the transformed cell lines , consistWe next asked whether the observed expression of L1HS-Ta in some cells results from the transcriptional activation of all or most L1HS-Ta genomic copies, or only of a few of them. As a first step, we mapped the genomic location of all L1HS-Ta elements in each cell line of our panel. To achieve this task, we adapted for deep sequencing an existing method termed ATLAS . In brieFull-length L1 elements contain internal sense and antisense promoters located in their 5'-untranslated region (UTR). To gain insight into the pattern of L1 expression in human somatic cells at single copy resolution, we noted that the weak L1 polyadenylation signal in the 3' UTR allows a fraction of L1 transcripts to extend into the downstream genomic sequence . This prTTC28 gene (22q12.1). Uniquely mapped RNA-seq tags are detected both in the body of the L1 sequence and in the immediate downstream genomic region. However, read mapping is performed against the reference human genome; thus, reads mapping within the L1 body could originate either from this particular reference L1 copy or from a non-reference L1 copy integrated somewhere else in the genome, and are therefore not informative. The second example is a non-reference L1HS-Ta element inserted in the NEDD4 gene (15q21.3) in opposite orientation. Again, a downstream RNA-seq peak immediately follows the insertion point. Interestingly, in both cases, we do not detect upstream antisense RNA-seq tags at the vicinity of these full-length L1HS-Ta copies, suggesting that sense and antisense L1 promoter activities - or the stability of their respective transcripts - are not necessarily coupled in a chromosomal environment, in agreement with previous results obtained from plasmid borne reporter assays . First, we observed H3K4me3 ChIP-seq peaks immediately upstream and adjacent to these L1 copies, a histone mark reflecting active or poised promoters  Bernste. AlthougTTC28 and NEDD4 loci + RNA-seq data were not available in public databases, As for MCF7, L1HS-Ta expression profiles between biological replicates of all cell lines are similar; and global shRNA-mediated ORF1 knockdown in 2102Ep, followed by RNA-seq, again confirmed the L1-derived origin of downstream transcripts in this cell line . The totvs. non-expressed elements were differentially oriented relative to the overlapping genes. Consistent with previous observations  among the 20 most highly expressed L1HS-Ta copies as deriving from the L1RP transduction family (Some L1 elements with high retrotransposition activity (‘hot’ L1) belong to well-defined lineages with distinctive 3’ transductions. To evaluate the proportion of the highly expressed elements which belong to such lineages, we screened 3’ ATLAS-seq reads supporting each L1 insertion for sequence tags characteristic of the three most characterized lineages  . We founn family . Nine adAltogether our observations support a model  where: .10.7554/L1 retrotransposon expression has been proposed both as a potential biomarker of cancer prognosis and as the starting point for L1-mediated genome instability in tumors . Hence, Furthermore, we provide here a unique resource consisting of near-complete maps of L1HS-Ta elements present in widely used normal and transformed model cell lines, for which the availability of genomic datasets is regularly increasing . These maps will be of broad utility in the future to address the impact and regulation of transposable elements in the human genome. Indeed, isolated RNA-seq and ChIP-seq signals resulting from the presence of non-reference L1 copies can only be correctly interpreted if such maps are available. Thus they can act as a platform to fully interpret and profit from the many expanding public datasets generated using the same cell lines.i.e. diminished restriction factor and/or increased cofactor activities , and 72°C for 10 min. A ~6 kb PCR product was resolved by 0.8% agarose gel electrophoresis, gel-purified using Wizard SV Gel and PCR Clean-Up System (Promega), and resuspended in 50 µL of milli-Q water. The second PCR was performed using 1 µL of the purified PCR product with primers matching the L1HS 5’ UTR (LOU1662) and the downstream flanking genomic DNA sequence of the L1 copy EXP_ID_0447 (LOU1664) with the following program: 98°C for 3 min, 40 cycles , and 72°C for 10 min. A PCR product of ~6 kb fragment was gel-purified as described above. Both primers of the second PCR contained homology in their 5’ parts to the CMV promoter and to the retrotransposition reporter cassette contained in the L1 expression vector pAD135 , allowin5 cells per well. The next day, cells were transfected with 1 µg of plasmid DNA and 3 µL of Lipofectamine 2000 (Life Technologies) diluted in 200 µL of Opti-MEM (Life Technologies), and medium was replaced with fresh medium after ~5 hr. Two days after transfection, medium was supplemented with G418 (Life Technologies) at 1 mg/mL. After 10 days of selection, colonies were fixed and stained with 1 mL of a solution containing 30% methanol (v/v), 10% acetic acid (v/v) and 0.2% Coomassie blue (m/v). The colonies obtained in three independent biological replicates were manually counted to assess the retrotransposition efficiency of pVan610 clones compared to the positive control pJM101/L1.3  and 2.8 µg of pCMV-VSV-G (Addgene #8454). Growth medium was changed 8 hr post-transfection. Two days after transfection, cells supernatants from 5 dishes were collected, pooled, filtered, and concentrated by overnight centrifugation at 4,000 rpm. Pellets were resuspended in 350 µL of growth medium, aliquoted and stored at -80°C until use. Viral stocks were titrated by colony formation assay upon puromycin selection  using serial dilution of vector stocks. For RNA-seq experiments, we infected 500,000 cells in triplicates (either MCF7 or 2102Ep cells) at M.O.I 1. Cells were collected for protein and RNA extraction after 1 week of puromycin selection (1.5 µg/mL).Annealed complementary oligonucleotides with 3' overhangs + RNA was isolated from the total RNA samples and fragmented with ultrasound (1 pulse of 15 s at 4°C). First-strand cDNA synthesis was primed with random hexamers. Then, the Illumina TruSeq sequencing adapters were ligated to the 5' and 3' ends of the cDNA. The cDNA was finally amplified with PCR using a proof reading enzyme and between 12 and 14 cycles. The TruSeq barcode sequences which are part of the 3' TruSeq sequencing adapters are included in www.ebi.ac.uk/arrayexpress) under accession number E-MTAB-4676 and E-MTAB-3788, respectively. RNA-seq data contain biological duplicates for untreated cells (two independent RNA extractions), and triplicates for shRNA-treated cells . The genomic locations of L1 insertions in the different cell lines are provided in Raw ATLAS-seq and RNA-seq data were submitted to the ArrayExpress database (http://www.bioinformatics.babraham.ac.uk/projects/fastqc/). Reads were trimmed using sliding-window mode from Trimmomatic (v0.32)  tool ( (v0.32) . The minhttp://broadinstitute.github.io/picard), after mapping a subset of the RNA-seq samples. The other mapping parameters were set to their default values.PE trimmed reads were aligned per lane to both the hg19 reference transcriptome and genome obtained from UCSC, using TopHat2 v2.0.13 . For a bThis section is related to http://www.broadinstitute.org/igv). Only the strand of first mates and with a MAPQ of 20 were taken into account, ensuring that only one read per fragment was counted and only pairs uniquely mapped were retained for downstream analyses. The window size was set to 10 and the window function used was the median. Coverage wig files from all libraries were normalized according to the total number of mapped mates 1 of each library. After normalization, wig files were converted to bigWig files using the command wigToBigWig (v4) from UCSC bioinformatics utilities. The bigWig files were used to identify transcriptional signals from the possibly full-length L1HS individual copies: RNA-seq signals upstream or downstream individual L1HS copies were used as a proxy to identify potential transcriptional signature of specific individual L1HS copies, as these genomic flanking sequences are more-often uniquely mappable. To obtain a global view of the transcription levels detectable at each LINE-1 locus, the computeMatrix command from deeptools (v1.5.9.1) was employed  were obtained from the RNA samples using SuperScript III Reverse Transcriptase (Life Technologies) as per the manufacturer’s instructions. Briefly, 1 µg of DNase-treated RNA samples were combined in a 13-µL reaction including 1 µL of a 10 mM dNTP mix, 1 µL of a 50 µM RACE primer and milli-Q water. The samples were incubated for 5 min at 65C and placed on ice for 1 min. The reactions were then supplemented with a 7-µL cDNA Synthesis Mix containing 4 µL of 5X First-Strand buffer, 1 µL of 0.1 M DTT, 1 µL of 40 U/µL RNaseOUT and 1 µL of 200 U/µL of SuperScript III RT. For each sample, a control condition was prepared without reverse transcriptase. The tubes were incubated for 50 min at 55°C and then for 15 min at 70°C. PCR amplification of the cDNA was obtained using Platinum Taq DNA polymerase (Life Technologies) as per the manufacturer’s instructions. Briefly, 1 µL of cDNA sample was combined in a 50-µL reaction with 1X PCR Buffer, 1.5 mM MgCl (RB3PA1 ), 0.2 µMhttps://support.illumina.com/sequencing/sequencing_software/igenome.html). When an L1 copy was inserted in a region corresponding to several overlapping genes oriented in the same direction, we considered the most expressed gene. Ploidy at each L1 insertion locus and for each cell line analyzed was determined using the copy number variation (CNV) tracks obtained from ENCODE (see ‘Data’ section). They were deduced from Illumina Human 1M-Duo Infinium HD BeadChip assays and circular binary segmentation (CBS), which segments the genome into amplified, normal, heterozygous deletion, homozygous deletion or uncovered regions. As expected, no L1 were inserted in region annotated as homozygous deletion. Uncovered regions were excluded from the analysis. The list of full-length L1 insertions provided in This section is related to  In the interests of transparency, eLife includes the editorial decision letter and accompanying author responses. A lightly edited version of the letter sent to the authors after peer review is shown, indicating the most substantive concerns; minor comments are not usually included.eLife. Your article has been reviewed by two peer reviewers, and the evaluation has been overseen by a guest Reviewing Editor, who acted as one of the reviewers, and Diethard Tautz as the Senior Editor.Thank you for submitting your work entitled "Activation of individual L1 retrotransposon instances is restricted to cell-type dependent 'hot loci'" for consideration by eLife readers. They also recommend some revisions as outlined below.The reviewers agree that your manuscript provides an important contribution to the field and will be of interest to The manuscript addresses a long-standing question in our field: Namely, how many and which of the many genomic LINE-1 loci contribute to expression at the RNA level. The authors do a very nice job of integrating different types of data: RNA-seq, epigenetic studies, and LINE-1 mapping with ATLAS, to reach conclusions about this. They take into account sense/antisense orientations and leverage that information in order to 'see' reads that span the L1 3' and 5' junctions with the adjacent genomic DNA. The attention to detail is high, and I think their conclusion – that a restricted subset of L1HS-Ta loci, a subset of which is polymorphic among individual cell lines, is responsible for the bulk of L1 expression – is sound.The following major points need to be addressed in a revision, before the paper can be accepted:More information should be provided on the positions of these active LINE-1 / contrast them to inactive loci. What are the surrounding genes and the relationship between the gene loci and the LINE-1? What is the ploidy/copy-number at these sites?More discussion is required on how the authors think their shRNA to ORF1 works. Their language  suggests they believe a shRNA silencing effect at the level of the genome is at work. One would think that shRNA is just causing degradation of the mRNA, which is what accounts for reductions in the reads.'Hot' is a colloquialism for retrotransposition active LINE-1. We would suggest the authors think of different terms, for example, expressed LINE-1 in place of hot LINE-1 when RNA levels are described, permissive loci in place of hot loci when considering epigenetic context. Keeping the narrow definition of 'hot' may avoid confusion in the literature.You should consider utilising the identification of daughter elements from their shared 3' transductions with putative progenitors as evidence of retrotransposition capability (where this was not assessed directly by cell culture assays). However you do not comment on the relationship between these transduction lineages and previously identified highly active pedigrees of elements. It is well established that common, highly active polymorphic L1 insertions, while showing significant allelic variation in retrotransposition activity, nevertheless frequently belong to lineages with distinctive 3' transductions. It would be valuable to know what proportion of the highly expressed elements analysed for their retrotransposition capability (either directly or by implication from ATLAS-seq reads) belong to previously identified lineages. It may be that the apparent dominance of small cohorts of elements is modulated by intrinsic features of these subsets of L1 elements. More information should be provided on the positions of these active LINE-1 / contrast them to inactive loci. What are the surrounding genes and the relationship between the gene loci and the LINE-1? What is the ploidy/copy-number at these sites?We have now compared the cohorts of expressed vs. non-expressed L1 copies with regards to:i) Their proportion in genes;ii) For the genic subset:– Their orientation relative to genes;– The levels of expression of their associated genes;iii) Their proportion in copy number variation regions.These analyses do not support a specific enrichment of expressed copies in genes or in amplified regions of the genome. For the genic copies, however, we found that expressed L1 copies are inserted in genes exhibiting higher levels of expression than inactive L1 loci.In the revised manuscript, these results are now shown in “To test whether the expression of L1HS-Ta copies could be influenced by their genic environment, we first compared the proportion of expressed L1 insertions in genes as compared to non-expressed copies. […] The majority of L1 copies were inserted in normal regions , whetherRelated additional information has been added in the Materials and methods section, and we appended an additional column containing gene names to More discussion is required on how the authors think their shRNA to ORF1 works. Their language  suggests they believe a shRNA silencing effect at the level of the genome is at work. One would think that shRNA is just causing degradation of the mRNA, which is what accounts for reductions in the reads.We agree that the title of 'Hot' is a colloquialism for retrotransposition active LINE-1. We would suggest the authors think of different terms, for example, expressed LINE-1 in place of hot LINE-1 when RNA levels are described, permissive loci in place of hot loci when considering epigenetic context. Keeping the narrow definition of 'hot' may avoid confusion in the literature.We agree that the use of ‘hot loci’ might be a source of confusion in the future. This was changed into ‘permissive loci’ in the title and throughout the manuscript, as appropriately proposed. Thus, the revised title is now: “Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci”. (Please see answer 9. on the choice of ‘instances’ instead of ‘insertions’ and answer 6. on the revised Discussion).You should consider utilising the identification of daughter elements from their shared 3' transductions with putative progenitors as evidence of retrotransposition capability (where this was not assessed directly by cell culture assays). However you do not comment on the relationship between these transduction lineages and previously identified highly active pedigrees of elements. It is well established that common, highly active polymorphic L1 insertions, while showing significant allelic variation in retrotransposition activity, nevertheless frequently belong to lineages with distinctive 3' transductions. It would be valuable to know what proportion of the highly expressed elements analysed for their retrotransposition capability (either directly or by implication from ATLAS-seq reads) belong to previously identified lineages. It may be that the apparent dominance of small cohorts of elements is modulated by intrinsic features of these subsets of L1 elements.We addressed this question in two different ways:i) First, we compared the list of full-length insertions, independently of their level of expression, with a published dataset of insertions deriving from the 3 main L1 lineages  . Eight out of 15 full-length and lineage-specific insertions found by MacFarlane et al. are present in the studied cell lines, but none of them belong to the top 20 highly expressed L1 .EDD4). Its affiliation to the RP lineage was confirmed by Sanger sequencing and its retrotransposition activity had already been tested by cellular retrotransposition in the initial version of the manuscript (now shown in ii) Second, we screened ATLAS-seq reads before poly(A) and L1 sequence trimming for the presence of lineage-specific sequence tags. This allowed us to identify the full-length L1 copies in our dataset belonging to these transduction lineages. Through this computational approach, we identified all 8 insertions previously found in the MacFarlane et al. dataset, as well as 2 additional insertions belonging to the RP lineage. One of these two insertions was ranked in the top 20 highly expressed L1s across all cell lines  belong to well-defined lineages with distinctive 3’ transductions. […]Thus, these findings suggest that the observed high level of expression of a small cohort of L1 insertions is not an intrinsic feature of any previously identified lineage.”Moreover, a new paragraph entitled “L1 lineage identification” has been added in the Materials and methods section.