The propagation length of the hybrid plasmonic waveguide varies from 0.14 μm to 20.43 μm by the voltage tunability of graphene in 1550 nm incident light. A modulator with a length of 3 μm is designed based on the hybrid waveguide and it achieves about 100% modulation depth. The lower energy loss (~1.71 fJ/bit) and larger 3 dB bandwidth (~83.91 GHz) are attractive for its application in a photoelectric integration field. In addition, the excellent robustness (error of modulation effects lower than 8.84%) is practical in the fabrication process. Most importantly, by using the method of adjusting propagation length, other types of graphene modulators can also achieve about 100% modulation depth. A modulator is the core of many optoelectronic applications such as communication and sensing. However, a traditional modulator can hardly reach high modulation depth. In order to achieve the higher modulation depth, a graphene electro-optical switch modulator is proposed by adjusting propagation length in the near infrared band. The switch modulator is designed based on a hybrid plasmonic waveguide structure, which is comprised of an SiO F) with electrostatic gating. Based on this excellent tunability of the absorption property   ,38, whereff/A0 can be given by Equation (3) [m refers to the total energy density and max {W} represents the maximum energy density of the structure. Smaller Aeff/A0 means stronger optical confinement in the devices. The consumed energy can be given by E = 1/4CVp2. C represents the total capacitance of the modulator, which is mainly composed of the quantum capacitance of graphene and the equivalent capacitance between graphene and Si. Vp refers to the peak-to-peak value of external voltage. The 3dB bandwidth of the modulator can be given by f3dB = 1/2πτRC = 1/2πRtotalC, where Rtotal refers to the resistance of the whole modulator. It is composed of the graphene resistance and the contact resistance between graphene and metal electrode. The resistance of graphene can be generally ignored because of the small value (about tens of ohms) [The normalized effective mode area Ation (3) :A0=λ2/4of ohms) .2 at 1550 nm incident wavelength are − 129 + 3.3i, 2.25 and 12.25, respectively [The modal properties of the presented modulator are investigated numerically by using the finite element method package in RF module of COMSOL Multiphysics 5.4 software . The modectively .In order to optimize the size of modulator, the normalized effective mode area and propagation length need to be calculated. By discussing the values of the normalized effective mode area and propagation, the optimal size of gap g and radius R can be decided.eff/A0 becomes larger with the increase of g. The main reason is that when g is large, the interface area between dielectric Si and Ag nanowire is not large enough to confine the light into a very small scale. The Lm becomes larger with the increase of g. The main reason is that the increase of g can bring the smaller interface area between dielectric Si and Ag nanowire, which will decrease the energy loss of incident light and bring the increase of Lm. m will increase with the larger R. The key factor is that the larger radius will cause a smaller loss of incident light and improve the propagation length. By contrast, larger R reduces the degree of light localization and results in a larger Aeff/A0. In fact, the results shows that larger Lm and smaller Aeff/A0 are contradictory in the devices. In order to obtain the larger Lm and keep Aeff/A0 as small as possible, the g is set to 1 nm and R is set to 50 nm. By tuning the refractive index of graphene, Neff will be changed and the propagation length can be adjusted for this switch modulator.It can be concluded from According to the result in p2, the energy loss of the whole switch modulator is ~1.71 fJ/bit. The total resistance mainly includes graphene resistance and the contact resistance between graphene and metal electrode. Because the resistance of graphene is too small (about tens of ohms) and can be ignored, the total resistance is 177.93 ohms. According to Equation f3dB = 1/2πτRC = 1/2πRtotalC, the 3 dB bandwidth of this switch modulator is 83.91 GHz.The total capacitance is mainly composed of graphene quantum capacitance and equivalent capacitance between graphene and Si. After calculation, the quantum capacitance of graphene is ~0.098 F/m and the equivalent capacitance between graphene and Si is ~0.0108 F/m. Due to the width and length of this switch modulator is 400 nm and 3 μm, its total capacitance is 10.66 fF. Moreover, 1.5 V and 2.3 V voltages are used to control the on and off for this switch modulator. According to Equation E = 1/4CVm) − min(Lm))/max(Lm). The maximum error of this switch modulator in 1.5 V is about 2.89% (g = 1 corresponds to the ~19.926 μm propagation length and g = 4 corresponds the ~20.502 μm propagation length). For the error of propagation length in 2.3 V, maximum error of this switch modulator is about 0.58% (g = 1 corresponds to the ~0.1396 μm propagation length and g = 4 corresponds to the ~0.1404 μm propagation length). As shown in It can be observed from 2. 10 nm thickness of Si upon the graphene layer is deposited as the substrate by atomic layer deposition, which can constrain the electric field distribution inside the device. Another layer of graphene can be transferred in the same way. Then, a SiO2 layer can be transferred onto graphene, which can be used as a cladding material for the gap between Ag and the upper graphene. In addition, the SiO2 layer is also used to grow a silver nanowire. Flipping the entire structure, by ion beam etching an SiO2 layer in a z direction definite size, a cylindrical hole can be etched out. After using the magnetron sputtering technology and masks technology, silver ions can fill empty slots in the cylinder to form the silver nanowire needed. Finally, flipping the entire structure to the original place, SiO2 cladding can be grown on the whole devices [The switch modulator can be manufactured with general commercial SOI wafers. Firstly, two grating couplers can be produced at both ends of the device by deep reactive ion etching (The cycle of grating couplers is set to 780 nm in 1550 nm working length), which can achieve the phase matching and let the incident light enter or output the switch modulator. Then a layer of graphene can be transferred onto 100 nm SiO devices ,42. In tIn this paper, a novel graphene electro-optical switch modulator based on adjusting propagation length is proposed in the near infrared band. It successfully combines the advantages of hybrid waveguide and the tunability of graphene to adjust the propagation length, which achieves ~100% modulation depth for the switch modulator in theory. The numerical simulations at the wavelength of 1550 nm show that GESMBOSN has relatively low loss (~1.71 fJ/bit) and very large 3 dB bandwidth (~83.91 GHz). In addition, the wonderful robustness of this switch modulator is also conducive to the actual application. Most importantly, with this new method to design a graphene switch modulator, other graphene switch modulators can also have the potential to arrive at about 100% modulation depth.


The thinning of thick Si substrate down to 50 µm has been performed prior to a multi-step milling of the conical-shaped micropore with final pore size of 3 µm. A transfer of graphene onto the fabricated conical-shaped micropore with little or no defect was successfully achieved using a newly developed all-dry transfer method. A circular shape graphene nanohole with diameter of about 30 nm was successfully obtained at beam exposure time of 0.1 s. This study opens a breakthrough in fabricating an integrated graphene nanohole and conical-shaped Si micropore structure for biosensor applications. A biosensor formed by a combination of silicon (Si) micropore and graphene nanohole technology is expected to act as a promising device structure to interrogate single molecule biopolymers, such as deoxyribonucleic acid (DNA). This paper reports a novel technique of using a focused ion beam (FIB) as a tool for direct fabrication of both conical-shaped micropore in Si Biosensors have attracted a great deal of attention for biological detection in the past three decades ; for exaGraphene, a two-dimensional nanomaterial, facilitated with a nanohole and integrated onto a solid-state micropore structure is considered as a promising alternative to realize a stable biosensor due to its one-atom thick layer and its extremely high surface-to-volume ratio, which enable it to be used as a highly sensitive membrane for the detection of biomaterials, such as DNA and protein ,21,22,23At first, the Si substrate (thickness: 525 µm) was cleaned with conventional organic treatment  water) to remove native oxides and contaminants on the substrate surface. 3N4) was deposited onto a Si substrate with a thickness of 100 nm using plasma-enhanced chemical vapor deposition (PECVD), as shown in I, were set at 2.1 and 9.3 nA for primary and secondary milling, while the ion beam voltage, V, was kept constant at 30 kV. It can be seen here that the primary milling was performed in a multistep manner where the milling diameter was changed at every milling step, as the upper diameter is always set larger than the bottom diameter so that the conical-shape of the micropore can be realized. At the primary milling, the diameter was changed in the condition that can be expressed as d1 > d2 > d3 >….> dn. The milling diameter was changed from 40 down to 15 µm, with the 5 µm in difference. Each milling step was carried out at the same depth value, zp, which is about 3 µm in depth. At the secondary milling stage, the milling was carried out in a single step. The value for ds and zs were always fixed to 3 and 1000 µm, respectively. The substrate with the micropore structure was characterized using scanning electron microscopy (SEM). Silicon nitride  and Raman spectroscopy (Witec Alpha 300 M+).I, of 9.3 and 2.1 nA, respectively. As shown in the For the results, first we present the dependency of the Si micropore’s shape and size with the change of the FIB milling current. Then, the dependency of the shape and size of the graphene nanohole as a function of the FIB milling time is described. The properties of the transferred graphene membrane on the Si micropore using the all-dry transfer technique is also presented. −1 and 2690 cm−1, respectively [2D/IG of 1.1 indicates that the transferred graphene layer is a bilayer graphene [−1, which indicates that clean and defect free graphene was successfully transferred by the all-dry transfer method.ectively . The intgraphene . No defeThe formation of the nanohole was performed in the transferred graphene on the Si micropore by a direct milling using the FIB. The Raman spectra was measured to confirm the nanohole formation in the graphene layer. In summary, a simple and reliable direct fabrication of a conical-shaped Si micropore and a graphene nanohole using a FIB was successfully demonstrated for the first time. A clean and defect free graphene was also successfully transferred accurately onto a micropore by a developed all-dry transfer method. This study opens a breakthrough towards the utilization of integrated graphene nanohole and conical-shaped Si micropore for biosensor applications.


The reactive nature of PE-ALD enables deposition of thin (2 nm) dielectrics directly on graphene and other two-dimensional materials without the need for a seed or functionalization layer; however, this also leads to significant oxidation of the graphene layer as observed by Raman. In FETs, we find this oxidation destroys conductivity in the graphene channel. By transferring thin (1.6 nm) MOCVD BN layers on top of graphene channels prior to PE-ALD, the graphene is protected from oxidation enabling BN/Al2O3 layers as thin as 4 nm. Raman and X-ray photoelectron spectroscopy on BN films show no significant oxidation caused by PE-ALD of Al2O3. Inserting the BN layer creates an atomically abrupt interface significantly reducing interface charges between the graphene and Al2O3 as compared to use of a 2 nm Al buffer layer. This results in a much smaller Dirac voltage (− 1 V) and hysteresis (0.9 V) when compared to FETs with the Al layer (VDirac = − 6.1 V and hysteresis = 2.9 V).Here, we investigate the use of few-layer metal organic chemical vapor deposition (MOCVD) grown BN as a two-dimensional buffer layer for plasma enhanced atomic layer deposition (PE-ALD) of Al The layered structure of these materials, with strong in-plane bonding and weak van der Waals inter-planar bonding, provides the ability to thin and stabilize them down to a single layer. Although, these materials have fully compensated surfaces with no dangling bonds; they are quite sensitive to the surrounding environment, including the substrate, ambient adsorbates, and in devices, the addition of component layers like-contacts, gate dielectrics, and passivation layers10. These can lead to oxidation, doping, and charge scattering severely degrading properties. In graphene, the effects of these surrounding elements have been shown to greatly impact basic transport properties and devices performance. To mitigate the effects of the substrate and adsorbates, a thin van der Waals (vdW) buffer layer, like hBN12, has shown to be extremely effective at preserving the properties of graphene.Devices based on two-dimensional (2D) materials offer great possibilities for applications requiring mechanical flexibility15; for which, atomic layer deposition (ALD) is ideally suited. However, 2D materials present a significant challenge to depositing ultra-thin, high quality, high-κ dielectrics due to the inherent lack of reactive surface nucleation sites16. To overcome these nucleation challenges, various surface functionalization and seeding layers have been used to promote ALD deposition. Surface functionalization by treatment with reactive species like ozone17, XeF218, and H2, O2, or N2 plasma21 produce functional surface groups and defects that provide nucleation sites. However, these functionalization methods partially convert sp2 C bonds in graphene to sp3 degrading properties, which can be in some cases recovered through annealing19. Nucleation can also be improved by functionalization with physisorbed molecules like H2O22 and NO223 followed by low temperature thermal ALD. Zheng et al.22 found the low temperature Al2O3 ALD layer to be low density and have low dielectric constant requiring deposition of a second higher temperature high quality layer. On the other hand, seeding-layers consisting of thin polymers24, metal-oxides26, or metals27 can be deposited by low impact methods, like evaporation, that minimize damage to the graphene layer. Functionalizing the graphene surface or inserting a seed layer between graphene and the ALD dielectric can introduce interfacial charges and traps, reduce the total dielectric constant of the gate stack, and limit the minimum equivalent oxide thickness (EOT)28. One alternative is to use a 2D buffer layer on top of the graphene to protect the interface during ALD30.The progression toward high performance 2D devices necessitates the integration with high quality thin dielectrics, for gates, tunneling barriers, etc.2O3 on graphene for top gated field effect transistors (FETs). PE-ALD offers a number of advantages over thermal ALD for deposition of dielectrics on 2D materials. Generally, the high reactivity of the plasma species allows for a wider range of materials to be produced, with higher quality, higher density, and at lower temperatures than thermal ALD31. Plasma species can also modify the surface promoting nucleation and greatly reducing nucleation delay critical for reducing gate thickness32. Additionally, PE-ALD enables more exotic coating and high-k dielectric that can reduce (EOT) even further33. For graphene and other 2D materials the plasma species can serve as in-situ functionalization eliminating the need for ex-situ functionalization or seeding required for thermal ALD of ultra-thin high quality layers; however, this occurs at the cost of damaging the 2D layer34. By transferring a thin (1.6 nm) BN layer on top of the graphene FET channel prior to PE-ALD of the Al2O3 gate dielectric, we demonstrate a weakly interacting 2D buffer layer that protects the graphene layer during PE-ALD. We find that depositing directly on graphene with no seed layer causes significant oxidation destroying the graphene channel, while devices with a BN buffer layer are preserved. These BN devices also have significantly lower shift in the Dirac point and lower hysteresis due to reduced interfacial doping at the BN/graphene vdW interface.In this paper, we investigate the use of 2D BN grown by metal organic chemical vapor deposition (MOCVD) as a thin buffer layer for plasma enhanced (PE) ALD of Al2O3 gate dielectric, Fig. 2O3 were explored: (1) no seed layer—PE-ALD directly on graphene, (2) transferred 2D BN on graphene followed by PE-ALD, (3) 2 nm e-beam evaporated Al seed layer followed by PE-ALD, and (4) transferred 2D BN layer followed by 2 nm e-beam evaporated Al seed layer and PE-ALD. Figure 2-plasma etching followed by e-beam deposition of Ti/Pt/Au ohmic contacts. An O2 plasma power of 200 W was used to selectively remove the graphene, while leaving the BN layer intact. For devices with the 2D BN layer a 1.6 nm thick BN layer was wet transferred on top of the defined graphene channel and contacts. BN layers were grown on 2″ sapphire wafers by MOCVD under self-terminating growth conductions, similar to the BN layer used on the substrates side, providing a large-area, highly reproducible and uniform 1.6 nm thick layer36. Figure 2/Si. After, the BN is transferred, the PMMA is removed, and the stack annealed to improve the graphene BN interface and clean the BN surface prior to ALD. Next, a 2 nm Al seed layer, excluded in buffer layer 1 and 2, is deposited followed by 20 nm of Al2O3 by PE-ALD and Ti/Au gate contacts.Top-gated graphene FETs were fabricated on chemical vapor deposition (CVD) graphene films transferred to 2″ MOCVD grown BN on sapphire substrates. A variety of FETs with gate lengths from 2.5 to 10 µm were used to investigate electrical characteristics of devices with different buffer layers for PE-ALD Al2O3 deposition on graphene’s structural quality. Figure 2O3 deposition. To compare the effect of the 2 nm Al layer, the graphene film was masked and Al was deposited on half of the sample. Compared to the as transferred spectra, the half without the Al layer shows a significant increase in defect related D/D’ peaks and reduction in the G’ indicative of the formation of graphene oxide37. The side with the 2 nm Al layer does not have the same increase in D and D’ indicating the layer serves to protect the graphene. AFM images  and morphology. Both layers appear to completely cover the graphene layer with no signs of nucleation issues, which is expected due to the in-situ functionalization caused by the O2 plasma.The advantages of PE-ALDs in-situ auto functionalization comes at the consequence of potentially damaging the graphene layer. Raman spectroscopy was used to investigate the effect of Alges Fig.  of Al2O32O3 gate dielectrics were deposited with no seed layer and the other half with the Al seed layer. Device characteristics were measured on one device with a 10 µm gate length per reticle. Figure D in the range of 0.7–2.1 mA/mm at Vds of 0.1 V. The oxidation observed in Raman clearly has a significant effect on the electrical conductivity of the graphene layer.To investigate the effect on device operation, a full 2 × 150 µm) graphene FET wafer was processed, in ~ half of the devices the Al × 150 µm35. To mitigate these interface effects we explore inserting a few layer thick sp2 bonded BN layer between the graphene and Al2O3 layer. Figure 2O3. BN is well established as an oxidation resistant coating even when thinned to only a few monolayers38, but how MOCVD/CVD grown films react to O2 plasma during PE-ALD is not established. AFM shows a uniform surface morphology with a roughness of ~ 0.5 nm  and N 1 s ( 397.8 eV) in good agreement with previous reports on sp2 bonded BN39 with no oxide related peaks around 193 eV (B–O)40. The lack of oxidation signatures in the BN layer indicates the BN layer could be thinned to below four mono-layers. With the established stability of the BN layers under the PE-ALD process, we now investigate its use as a buffer layer for protecting graphene. Figure 2O3 on bare graphene and graphene covered with the BN buffer. As observed in Fig. 2O3 oxidizes the graphene layer, but by covering the graphene with a thin BN layer the graphene is preserved with little change in the Raman. This can even be observed optically  structures from each region  from vdPs with the BN buffer, Al seed layer, and both the BN and Al seed layer of − 9 × 1011, − 3 × 1012, and − 7 × 1012 cm-2 and Hall mobility of 890, 560, 1,060 cm2/Vs. To check that the buffer type does not impact the gate leakage current (IG), we measure IG as VG is swept from − 8 to 4 V at Vds of 0.5 V. Figure G for all gate types, between 12 and 16 pA, demonstrating consistent insulating behavior of the gate dielectric independent of buffer type.To compare the effect of the 4 buffer types on FET performance, we fabricated a full wafer with top gates fabricated using each type, Fig. Dirac due to n-type doping and similar peak transconductance of 30 µS or better. Upon the reverse VG sweep, hysteresis with a positive shift in VDirac is observed in Ids–VG, which is common in graphene FETs. This shift is due to negative charge traps at the graphene interface from defects in the dielectric and/or contamination 43. The effect of interface contamination can be reduced by processing under vacuum or inert environments, cleaning processes, annealing, or by inserting a 2D buffer layer, like BN. Indeed, if we compare transfer curves from each buffer type, we observe VDirac and hysteresis depend strongly on the buffer type with the lowest doping and hysteresis in devices with a BN buffer  at 20 °C for up to 2hrs. Released films were wet transferred, dried in air, followed by the PMMA removal with acetone, and finally annealed in 5% H2:N2 forming gas at 400 °C for 30 min. Graphene grown on copper by CVD using methane as the carbon source were transferred to the BN/sapphire substrates using a typical wet transfer with PMMA, similar to the process described in Ref.44.Boron Nitride on 2″ sapphire substrates and transferred films used in this study were grown by metalorganic chemical vapor deposition (MOCVD) at 1,000 °C, 20 Torr and B/N ratio of 2250 for 30 minThe surface morphologies of graphene and BN layers were analyzed by AFM using a Bruker Dimension Icon in tapping mode. Raman measurements of graphene and BN were performed using a Renishaw inVia system under a backscattering geometry. A 488 nm excitation source at 4 mW, 20 µm slits, and a 3,000 l/mm grating was used for these measurements. Chemical analysis of films was performed using X-ray photoelectron spectroscopy .2-plasma. Source and drain Ti/Pt/Au contacts were evaporated. A 20-nm thick Al2O3 top gate dielectric was deposited by ALD. ALD was performed at 250 °C with half cycles of trimethylaluminum and a remote 300 W oxygen plasma, achieving a growth rate of 0.94 A/cycle. Gate metal (Ti/Au) contacts were defined using a second lift-off process31. The automated electronic characterization was performed using a Cascade Summit 12 k probe station with an HP 4142 parameter analyzer and GSG probes.Graphene FETs were fabricated using transferred CVD graphene on BN/sapphire. The graphene mesas were etched using an OSupplementary Information.


Here, we succeed in stabilizing pure-phase ε-Fe2C nanocrystals by confining them into graphene layers and obtain an iron-time yield of 1258 μmolCO gFe−1s−1 under realistic FT synthesis conditions, one order of magnitude higher than that of the conventional carbon-supported Fe catalyst. The ε-Fe2C@graphene catalyst is stable at least for 400 h under high-temperature conditions. Density functional theory (DFT) calculations reveal the feasible formation of ε-Fe2C by carburization of α-Fe precursor through interfacial interactions of ε-Fe2C@graphene. This work provides a promising strategy to design highly active and stable Fe-based FT catalysts.The development of efficient catalysts for Fischer–Tropsch (FT) synthesis, a core reaction in the utilization of non-petroleum carbon resources to supply energy and chemicals, has attracted much recent attention. ε-Iron carbide (ε-Fe 2C has been identified as the highly active phase for Fischer-Tropsch synthesis (FTS), but is stable only at low-temperature. Here, the authors show that ε-Fe2C phase can be stabilized even at ~ 573 K by being encapsulated inside graphene layers, and retains high activity in FTS.ε-Fe Because FT synthesis is a core reaction in the utilization of various non-petroleum carbon sources  to supply energy and chemicals, the development of efficient FT catalysts has received much-renewed interest in recent years6. Iron-based catalysts have widely been used in the industrial FT process because of the low cost of iron, wide operation conditions, and flexible product distributions7. However, Fe-based catalysts usually suffer from low activity and stability3, and thus many recent fundamental studies have been devoted to enhancing the FT activity and stability of Fe catalysts by employing different modifiers or different supports14. Unlike Ru- or Co-based FT catalysts, where metallic Ru0 or Co0 functions as the active phase, metallic Fe0 is unstable and the evolution of a conventional Fe-based catalyst typically results in a mixture of different iron phases including Fe3O4 and iron carbides under FT reaction conditions21. Iron carbides are believed to be responsible for the activation of CO and the chain growth in FT synthesis, but the nature of the true active iron-carbide phase is still under debate and this hinders the rational design of highly active and stable Fe-based FT catalysts.Fischer–Tropsch (FT) synthesis transforms syngas  FT reaction29. The Fe catalyst based on ε-Fe2C phase could also decrease the CO2 selectivity during FT synthesis30. However, it is known that ε-Fe2C would be transformed into χ-Fe5C2 at above 523 K, and thus would be unstable at a higher temperature (~573 K) that is usually adopted for Fe-catalyzed FT synthesis. Under FT reaction, Fe-based catalysts are usually coated with an amorphous carbon/carbide layer that facilely induces the carbides transformation  can stabilize this metastable phase for FT synthesis at 523–613 K. The Fe-time yield (FTY), which is defined as the moles of CO converted to hydrocarbons per gram of Fe per second, reaches 1258 μmolCO gFe−1 s−1 at 613 K, breaking the upper-limit value (1000 μmolCO gFe−1 s−1) reported for Fe-based FT catalysts13. The catalyst is highly stable under our FT reaction conditions and high CO conversion (~ 95%) can be kept at 573 K at least for 400 h. DFT calculations suggest that the confinement effects of graphene layers favor the formation of ε-Fe2C from carburization of α-Fe, which maintains the high stability of ε-Fe2C under high-temperature FT reaction conditions. On the other hand, the facile transformation of FexC particles may occur during FT synthesis over the conventional FT catalyst. To the best of our knowledge, this is the first example to demonstrate experimentally that the ε-Fe2C phase can be stabilized under high-temperature FT reaction conditions. The present work provides a promising strategy to synthesize highly active and stable Fe-based FT catalysts and offers an opportunity for the study of FT reactions on pure metastable-phase iron carbides.Here, we attempt to replace the amorphous carbon with few graphene layers that confines the Fe-based catalyst. The confinement of the rigid geometry of the graphene shell can inhibit the formation of the amorphous carbon layer and improve the stability of highly active ε-Fe2C Fig. . We repo2 and carburization in syngas flow. X-ray diffraction (XRD) measurements and 57Fe Mössbauer spectroscopy showed that θ-Fe3C was the major Fe phase in the precursor obtained after pyrolysis  facet of θ-Fe3C and the (002) facet of graphene, respectively, were observed . It is of interest that ε-iron carbide (ε-Fe2C) rather than θ-Fe3C or χ-Fe5C2 was formed after the carburization  on the 2D material overlayers, which mainly follow the defect-aided intercalation mechanism34. In addition, the Raman spectra of ε-Fe2C@graphene catalyst show that the 2D peak position of ε-Fe2C@graphene blueshifted relative to single-layer graphene and the peak pattern consistent to the few graphene layers rather than bulk graphite , the ε-Fe2C content remained constant (about 62.8%), indicating the stabilizing effect by the graphic carbon layer on ε-Fe2C even under reaction conditions  as explained in the computational details of 2C inside graphene layers can keep it from phase transformations probably.To gain further insights into the possible evolution of iron phases, we have performed in situ XRD characterizations for our sample in syngas flow under different conditions. α-Fe was still the major phase under syngas with a H3 K Fig. . In addi3 K Fig. . It is n3C@graphene samples before and after treatment under different conditions  and the G-band (graphene carbon), respectively . The θ-Fe3C@graphene , indicating unique defect-rich structure graphene layers after the annealing process. Moreover, the XPS results clearly confirmed the presence of defective graphene layers during the reducing and carburization processes  of ε-Fe2C is ~6–10 times higher than the θ-Fe3C and 2 times higher than the χ-Fe5C2. Furthermore, CO-TPD profiles of ε-Fe2C@graphene catalyst show a multi-peak overlapped cure with a maximum peak position at ca. 843 K, which is attributed to desorption of CO after recombination of dissociated carbon and oxygen on the surface  under the same reaction condition. On the other hand, the FTY value of reference Fe/C catalysts decreased sharply upon increasing Fe loading probably due to the aggregation of Fe species and the oxidation of the active carbide phase under reaction conditions  was increased to 160 L gcat−1 h−1 at 613 K  with different GHSVs revealed that the ε-Fe2C@graphene is much more active than χ-Fe5C2 in FT synthesis, as shown in Supplementary Fig. 2C@graphene was completed during 50 h at GHSV of 64.0 L gcat−1 h−1. For evaluation of catalyst deactivation, we have performed long-termed FT reactions for both ε-Fe2C@graphene and un-encapsulated χ-Fe5C2 catalysts at 573 K under harsh conditions . Further, the pressure drop across the ε-Fe2C@graphene catalyst bed was negligible even at high conversion, indicating that the coke deposition on this catalyst was significantly suppressed by the graphene layers under harsh condition.Time-on-steam evolution of CO conversion for ε-Feons Fig. . The CO 2C@graphene catalyst follows the Anderson-Schulz-Flory distribution  is relevant in describing the thermodynamics of iron carbides, which can be determined from the equilibrium of carburization reactions of different gas atmospheres for pretreatment or FT reaction at some temperatures and pressures. Higher temperature and lower pressure, as well as higher H2/CO ratio, result in lower ΔμC value indicating a lower carburization ability  can be derived for describing the carburization reaction from metallic Fe to iron carbide. The volume-normalized carbon absorption energy (Ωabs) was applied to the bulk iron carbides20.The effects of a graphene layer on the surface stability and carburization feasibility of ε-Feity Fig. . Based oωabs), which is suitable for describing the surface carburization of iron carbide with and without graphene confinement. The most abundant (101), (1-21), and (2-21) surfaces were selected to evaluate the confinement effects of graphene layers on the ωabs  > (1-21) > (2-21) according to the calculated surface energy  show similar results to those of graphene.On the other hand, the confinement effects are modeled by covering the ε-Fe3 Å Fig.  close to2C surface with and without graphene confinement. Both the direct and H-assisted dissociations are considered including different active sites of perfect ε-Fe2C, graphene, and the C-vacancy on ε-Fe2C  of ca. 1.2 eV than those of direct and H-assisted dissociations (2.57-2.61 and 2.83-2.87 eV) on the perfect ε-Fe2C surface with and without the confinement of graphene. The CO dissociation on the graphene site hardly occurs due to the high Ea values (> 2.89 eV). Similar results can be found for graphene-N. The confinement of graphene or graphene(-N) favors to improve the stability of the highly active ε-Fe2C to achieve the high catalytic performance of FT at high temperature.In addition, taking (1-21) as an example, we further investigate the mechanism of CO dissociation on the ε-Fe2C nanocrystals for the FT reaction. It exhibited remarkably activity (~ 1258 μmolCO gFe−1 s−1) and stability (>400 h) under realistic FT synthesis conditions. The confinement effects of graphene layers stabilize the metastable but very active ε-Fe2C phase. The unique confinement structure (ε-Fe2C@graphene) can inhibit the formation of an amorphous carbon layer that converts catalytically active ε-Fe2C phase to other less active carbide phases . Our results and conclusion could help in the rational design of promising active phases in industrial catalysts for hydrogenation processes.In summary, we synthesized graphene layers encapsulated ε-Fe3)3•9H2O. In a typical synthesis, an amount of Fe(NO3)3•9H2O, corresponding to the final Fe loading of 30–60 wt%, was mixed with 5.0 g urea and 3.0 g glucose at 393–433 K to form a transparent solution. The resultant molten mixture was heated at 453 K in an oven for 24 h. The solid collected was subjected to a heat treatment in flowing N2 (10 mL min−1) at 673 K for 30 min and finally at the final temperatures (773–1023 K) for another 2 h.The iron carbide nanocomposites were synthesized by pyrolysis of a molten mixture of urea, glucose, and Fe(NO3C@graphene samples obtained above were reduced in a flow of 3 L gcat−1 h−1 of H2 at 623 K for 3 h (denoted as Fe@graphene), and then the carbonization in a flow of 64 L gcat−1 h−1 of syngas (H2/CO = 1) at 573 K for 10~400 h (denoted as ε-Fe2C@graphene).The θ-FeThe size and morphology of samples were determined using a FEI Tecnai G20 transmission electron microscope operated at 200 kV and a Hitachi SU8000 field emission scanning electron microscope at an accelerating voltage of 15 kV.57Fe Mössbauer measurements were performed at room temperature or 77 K using a conventional spectrometer  in transmission geometry with constant acceleration mode. A 57 Co(Rh) source with an activity of 25 mCi was used. The velocity calibration was done with a room temperature α-Fe absorber. The spectra were fitted by the software Recoil using Lorentzian Multiplet Analysis. The samples were passivated in flowing 1% O2/N2 for 1 h at room temperature prior to air exposure and being sealed in a sample holder with paraffin wax for Mössbauer spectroscopy measurements.The 2/CO = 1) at 573 K for 5 h. Subsequently, the adsorbed species were removed by flowing He at 823 K for 2 h. The samples were cooled to 308 K, then CO chemisorption experiment was conducted. The average CO:Fe stoichiometry was assumed 1:2. For θ-Fe3C@graphene catalyst, reduction and carburization processes are eliminated.The CO chemisorption was performed using a Micromeritics AutoChem II 2920 unit. Before CO chemisorption, 0.1 g of catalyst was reduced under flowing pure hydrogen at 623 K for 3 h and then carburized in syngas (H2/CO = 1) at 573 K for 5 h. Subsequently, the adsorbed species were removed by flowing He at 573 K for 2 h. The samples were cooled to 308 K. At this temperature, the carburized sample was flushed with CO for 1 h and consequently purged with He until the baseline of CO signal leveled off. Finally, the sample was heated to 1,073 K at a ramp of 10 K min−1. For θ-Fe3C@graphene catalyst, reduction and carburization processes are eliminated.For CO temperature-programmed desorption (CO-TPD), 0.1 g of catalyst was reduced under flowing pure hydrogen at 623 K for 3 h and then carburized in syngas (HX-ray diffraction (XRD) patterns of the samples were recorded on a Bruker D8 powder diffractometer equipped with a Cu-Kα source operated at 40 kV and 40 mA and a Vantec-1 detector.Kα radiation operated under vacuum (2 × 10−6 Pa) with the binding energy (BE) calibrated using the C 1s peak at 284.6 eV.X-ray photoelectron spectroscopy (XPS) measurements were conducted on a VG Multilab 2000 photoelectron spectrometer using Al −1) with a ramping rate of 10 K min−1.Thermogravimetric analysis (TGA) was carried out on a NETZSCH TG 209F3 TGA analyzer during temperature ramping from 303 K to 1,173 K in flowing air (50 mL min2 (10 mL min−1) at 623 K for 3 h before reactions. The pre-treated catalysts were cooled to 373 K in flowing H2 before the introduction of syngas (H2/CO = 1). The reaction temperature was then ramped slowly to 593 K. The permanent gases  and light alkanes  in the effluent of the reactor were monitored by an online Agilent Micro GC3000A gas chromatograph (GC) equipped with the molecular sieve, Plot-Q and Al2O3 capillary columns and a TCD detector. The oil and wax products were separated using a cold trap (271 K) and a hot trap (423 K), respectively, while the aqueous products were obtained by phase separation in those traps. The oil products were analyzed using an Agilent 6890N GC with a FID detector and a HP-5 column; the wax products were dissolved in CS2 and analyzed using an Agilent 7890A GC equipped with a FID detector and a HT5 column; the aqueous fraction was analyzed using an Agilent 4890 GC equipped with a FID detector and a HP-Innowax column. The product selectivity was calculated based on the carbon balance.Fischer–Tropsch synthesis was performed in a stainless steel fixed-bed reactor (i.d. = 12 mm). Catalysts were diluted with inert SiC particles in a mass ratio of 1:10 prior to testing. The diluted catalysts (5.5 g) were pre-treated in flowing H44 and projector-augmented wave (PAW) method45 as implemented in the Vienna ab initio simulation package (VASP)46. A second-order Methfessel–Paxton electron smearing scheme (sigma = 0.2 eV) was used because of the metallic conductor properties of iron carbide. Plane-wave kinetic energy cut off of 400 eV is sufficiently accurate for the spin polarization calculations of the electronic properties of open-shell iron carbide. Energy and force convergence criteria were 10−5 eV and 0.03 eV Å−1, respectively. The most abundant ε-Fe2C(1-21), ε-Fe2C(101), and ε-Fe2C(2-21) surfaces were taken into account. A vacuum of 15 Å was used for screening the interactions vertical to the surface. The most stable configurations were selected to model the confinement effects of graphene and N-doped graphene (graphene-N) on the carburization feasibility of ε-Fe2C from metallic iron and the reaction mechanism of CO dissociation. The computational details are deposited in Density functional theory calculations were performed using the generalized gradient approximation Perdew–Burke– Ernzerhof of (PBE) functionalSupplementary Information


Environmental safety has become increasingly important with respect to hydrogen use in society. Monitoring techniques for explosive gaseous hydrogen are essential to ensure safety in sustainable hydrogen utilization. Here, we reveal molecular hydrogen detection mechanisms with monolithic three-dimensional nanoporous reduced graphene oxide under gaseous hydrogen flow and at room temperature. Nanoporous reduced graphene oxide significantly increased molecular hydrogen physisorption without the need to employ catalytic metals or heating. This can be explained by the significantly increased surface area in comparison to two-dimensional graphene sheets and conventional reduced graphene oxide flakes. Using this large surface area, molecular hydrogen adsorption behaviors were accurately observed. In particular, we found that the electrical resistance firstly decreased and then gradually increased with higher gaseous hydrogen concentrations. The resistance decrease was due to charge transfer from the molecular hydrogen to the reduced graphene oxide at adsorbed molecular hydrogen concentrations lower than 2.8 ppm; conversely, the resistance increase was a result of Coulomb scattering effects at adsorbed molecular hydrogen concentrations exceeding 5.0 ppm, as supported by density functional theory. These findings not only provide the detailed adsorption mechanisms of molecular hydrogen, but also advance the development of catalyst-free non-heated physisorption-type molecular detection devices. Detection of molecular hydrogen in ambient atmospheres has become increasingly important because renewable energy, especially hydrogen-based energy, is a focus for the development of sustainable societies ,2. Users2O, CO, CO2, NO, NO2, O2, SO2, and NH3 at parts per billion (ppb) and parts per million (ppm) levels [2) using either graphene or rGO flakes is not precisely discussed in the literature because the weak physisorption strength and insufficient molecular detection area of the graphene surface mask the details of the electrical resistance behaviors. Since catalytic H2 detection with Pt [2 [2, the significant challenge of realizing physisorption of non-polar H2 and revealing the detection mechanisms in detail remains in the development of non-catalytic H2 detection devices.Conventional molecules are detected by catalytic combustion, resistance change, and thermal conductivity change ,4,5,6,7.) levels ,11,12,13) levels ,17,18,19 with Pt ,21, Pd [ with Pt ,23,24,25 with Pt , ZnO [27 with Pt , and SnOth Pt [2 ,30 at hi2 as compared to pristine nanoporous unoxidized graphene and rGO flakes. Such physisorption detection mechanisms based on a large surface area provide a new class of design direction for non-heated, flow-type, and physisorption-type graphene-based detection systems for non-polar gas molecules without metal catalysts.Here, we synthesized a single and monolithic nanoporous reduced graphene oxide (np-rGO) sheet. The synthesized sheet had an edge-free bicontinuous and open porous three-dimensional (3D) structure and was treated by a modified Hummer method. The np-rGO sheet maintained a projected surface area 500 times larger than that of a standard two-dimensional (2D) graphene sheet, performing significantly accurate detection via molecular physisorption of H30Mn70 ingots were prepared by melting pure Ni and Mn (purity >99.9 at.%) in an Ar-protected arc melting furnace. After annealing at 900 °C for 24 h for microstructure and composition homogenization, the ingots were cold-rolled into thin sheets (50 μm) at room temperature. Nanoporous Ni was prepared by chemical dealloying in a 1.0 M (NH4)2SO4 aqueous solution at 50 °C overnight. After dealloying, the samples were rinsed thoroughly with distilled water and then rinsed with ethanol before vacuum drying.Ni2) for 3 min [2 (100 sccm), Ar (200 sccm), and benzene  was introduced for graphene growth at 800 °C for 2 min. Subsequently, the furnace was opened for the rapid cooling of the inner quartz tube. The nanoporous Ni substrate was etched in a 1.0 M HCl solution and then the remaining nanoporous graphene was transferred into a 2.0 M HCl solution to completely remove residual Ni. The samples were repeatedly washed with water and subsequently kept in water.The nanoporous Ni substrates were loaded in a quartz tube (Ø26 × Ø22 × 250 mm), placed in a quartz tube furnace (Ø30 × Ø27 × 1000 mm), and annealed at 800 °C under a mixed gas flow , concentrated H2SO4 (3.45 mL), and NaNO2 (0.075 g) mixture without stirring. After 10 min, the mixture was diluted in an aqueous H2SO4 (5%) solution. Then, an aqueous H2O2 (30%) solution diluted in aqueous H2SO4 (5%) was slowly added to the mixture. The obtained transparent sheet was then washed several times with a mixture of aqueous H2SO4 (3%) and H2O2 (0.5%). The nanoporous graphene oxide (GO) sheet was then repeatedly washed with water and kept in 2-propanol. The samples were dried by a conventional supercritical CO2 drying method. The dried GO sample was transferred onto a SiO2 substrate and then connected to fine Cu lines (twisted) using silver paste in a standard pseudo four-probe configuration. The reduced graphene oxide (rGO) sample was prepared by annealing the GO sample on the substrate at 150 °C using ribbon heaters under vacuum in a self-made atmosphere-controlled glass cell connected to Swagelok vacuum components.The nanoporous graphene dispersed in water was oxidized via a modified Hummer method . A singl2 (scCO2) and thus 2-propanol was substituted for CO2 without the action of capillary forces. To this end, the nanoporous graphene sample was firstly transferred to a vial (volume: 5 mL) filled with 2-propanol (400 μL), and then the bottle was placed in an 80-mL pressure-resistant container (TAIATSU techno Corp). After removing the air inside the container via CO2 purging, the pressure of the container was gradually increased to 15 MPa by introducing liquid CO2  at a flow rate of 20 mL min−1 (~19 g min−1) using a high-pressure plunger pump . The scCO2 drying process was performed at 70 °C and at a constant CO2 flow rate of 5 mL min−1 (~4.8 g min−1) by forming a homogeneous phase of 2-propanol and scCO2, thus minimizing the capillary force. The pressure was maintained at 15 MPa for 5 h during the drying process. After drying the sample completely, the temperature was set at 40 °C and the container was gradually depressurized over 43 h from 15 MPa to atmospheric pressure by gradually pumping CO2 from the system. To prevent the collapse of the fragile nanoporous structures caused by water capillary forces during drying, the nanoporous graphene and rGO samples immersed in 2-propanol were dried by using supercritical COKa X-ray monochromator. Raman spectra were obtained using a micro-Raman spectrometer (Renishaw InVia Reflex 532) with an incident wavelength of 532.5 nm. The laser power was set at 0.1 mW to avoid possible damage or unexpected reduction by laser irradiation. The graphene samples were placed on a background-free glass slide. The accumulation time of each spectrum was 100 s. The microstructures of the nanoporous GO and nanoporous rGO were characterized using a scanning electron microscope . Chemical analyses on the graphene samples were performed via X-ray photoelectron spectroscopy  with an Al 2/Si (SiO2: 300 nm) substrate. The electrode was fabricated using Ag epoxy . The electrical resistance measurements were performed using the Physical Properties Measurement System .The temperature and magnetic field dependences of the electrical resistance of reduced nanoporous graphene oxide were measured using the four-probe method under a magnetic field at 300 K. The reduced nanoporous graphene sheets were placed on a SiO® to avoid leakage. The detection element of the nanoporous GO sheet (7.2 mm × 2.5 mm) was attached on a SiO2 substrate through fine twisted Cu lines fixed with silver paste. Then, the substrate was transferred to the glass cell and the fine Cu lines were electrically connected to the Cu wires (1.5 mm) inside the cell. The temperature inside the cell was controlled by an external ribbon heater for thermal reduction of nanoporous GO in the cell. The whole system and the connected vacuum components were heated to 150 °C, and the GO  through the fine Cu wires) was thermally reduced to rGO under vacuum (5 Pa). Briefly, the temperature for thermal reduction was fixed at 150 °C and the heating time was set at 4 h for oxygen contents of 20.0 at.%, 6 h for oxygen contents of 18.2 at.%, and 12 h for oxygen contents of 10.8 at.%. After cooling down to the room temperature (23 °C), the thermally reduced GO samples were sequentially measured in the cell by a standard pseudo four-probe method using a semiconductor parameter analyzer (Keysight B1500A). The applied voltage was set at −9 V for the nanoporous rGO samples  and to −10 mV for the pristine nanoporous graphene (without oxidation and reduction treatments) under a mixture of gaseous argon . The ultrapure gaseous Ar continuously flowed until the resistance value stabilized to exclude unexpected influences of impurities such as H2O, O2, CH4, CO2, CO, and H2. Thus, any changes in resistance values under the mixture of H2/Ar gas flowing could be attributed to the introduction of ultrapure H2 gas. After the resistance was stable, the mixture of gaseous Ar and gaseous hydrogen  was introduced in the cell. The total flow rate of the mixed gas was set at 30 sccm. To obtain the 1 ppm H2 gas in the Ar flow case, gaseous hydrogen was mixed with gaseous argon to a H2 concentration of 0.0001 vol.%, and then the mixed gas was supplied by the mass flow controllers at a flow rate of 30 sccm . Note that flow rates exceeding 30 sccm deformed the atomically thin porous structures, and the resistance values became unstable. Before all measurements, the whole system was vacuumed for 12 h at room temperature to avoid further thermal reduction of the rGO. A molecular detection glass cell was fabricated using an atmosphere-controlled separable three-neck glass cell with an O-ring. Swagelok vacuum components were inserted into two rubber stoppers, and the stoppers were installed in two of the necks. The Swagelok vacuum components were connected to mass flow controllers and a rotary pump. Four Cu wires (1.5 mm) and a thermocouple (type K) were inserted in a rubber stopper, and the stopper was installed in the third neck of the cell to communicate the inside and outside of the cell and the device; all connections were completely sealed with Torr Seal54H18, C54H18-2OH, C54H18-2O, C53H18-COOH, and C53H18-2O) were optimized using the density functional theory (DFT) method with the B3LYP functional [2 adsorption. All calculations were performed using Gaussian 16 quantum chemistry software [The geometries of the surface models  of 2.5 and of the D and G bands (ID/IG) of 0.08, corresponding to high-quality 1–2 layer graphene without detectable amorphous carbon features [ID/IG of 1.6 and I2D/IG of 0.91). The np-rGO partially restored graphene features (ID/IG of 0.98 and an I2D/IG of 1.7). The full width at half maximum (FWHM) values of the D, G, and 2D bands of the np-rGO were significantly increased in comparison to the pristine nanoporous graphene. Chemical binding was further investigated by XPS. The C1s X-ray photoelectron spectrum (sp2 and sp3 [ID/IG from the Tuinstra–Koenig relation: ID/IG = C(λ)/LD, where C(λ) is a proportionality constant at the excitation laser wavelength λ and LD is the average distance between the defects [LD value of np-rGO with an oxygen content of 20 at.% (ID/IG = 0.98) was approximately 8–10 nm, which was almost of the same order as the distance between the oxidized functional groups estimated by the atomic concentrations.Raman spectra were analyzed to estimate the quality of the graphene samples and their respective oxidation levels . The prifeatures ,44. Aftespectrum  demonstr and sp3 ,47. Ther defects ,49,50. U−1 and 5000–8000 cm2 V−1 s−1, respectively [−1 and 0.31–1.0 cm2 V−1 s−1, respectively [2 V−1 s−1) [The transport properties of nanoporous graphene and np-rGO were measured at 300 K by a standard four-probe method. The typical electrical conductances and electron mobilities of the nanoporous graphene samples were 500–1000 S cmectively ,51. The ectively . Note thV−1 s−1) . Therefo2, we measured the time dependence of resistance changes under the H2/Ar mixed gas in the atmosphere-controlled glass cell. Firstly, we confirmed the reversibility of molecular physisorption of H2 under Ar and H2/Ar flow conditions . The response was relatively slower than that of conventional catalytic metal-based gas detection systems, probably because the replacement of Ar by H2 requires time owing to the low flow rate and geometrically requires time to reach the surface due to the complicated porous structure [To evaluate the molecular physisorption ability of Htructure  in compatructure ,28,29,302 gas volume concentrations from 0.1 ppm to 10,000 ppm under H2/Ar gas flow  was investigated for the np-rGO with an oxygen content of 20.0 at.%  and plotted for the various H2 ppm values  showed a similar behavior but did not show large changes in resistance values for 0.1–10,000 ppm H2 under the same conditions. Thus, the large changes in np-rGO were attributed to the oxidized functional groups on the graphene. Moreover, both samples exhibited a local minimum at approximately 1 ppm H2 under H2/Ar gas flow. Note that these increases and decreases have not been reported for graphene and rGO detection systems [2 ppm values under H2/Ar gas flow in comparison to the np-rGO sample with an oxygen content of 20.0 at.%. The change in resistance at H0.0 at.%  and nano0.0 at.% c. We foum values d. The no systems ,17,18,192 on the surface of graphene and graphene oxide , and there were no significant differences in the functional groups. In the models, it was found that two kinds of charge transfer phenomena occurred: (1) from oxygen-containing functional groups to graphene oxide  and (2) from a single H2 molecule to graphene oxide with +0.020 e   and lowest unoccupied molecular orbital (LUMO) decreased after the adsorption  and a charge transfer (+0.074 e by four H2 molecules) from the additional H2 molecule on graphene oxide further occurred  . This susorption . In partoccurred .2 lower than 1 ppm showed negative resistance changes, while those higher than 5 ppm showed positive resistance changes. The high resistance changes are attributed to the high oxidation level of the samples . Below 1 ppm H2, contribution of Coulomb scattering by the adsorbed H2 was not dominant/apparent and the charge transfer from H2 to np-rGO was a major effect. In this case, further hole doping from the adsorbed H2 of the p-type np-rGO reduced the resistance  and gradually increased after 300 s (Coulomb scattering domination) with an increase in hydrogen concentration  showed the largest change of resistance values at higher H2 ppm values in comparison to the nanoporous graphene and np-rGO with oxygen contents of 10.8 at.% (hydroxyl/epoxide group: 2.5 at.%) and 18.2 at.% (hydroxyl/epoxide group: 6.3 at.%). Furthermore, open porous structures with large total surface areas whose surface was modified by the oxygen-containing functional groups significantly promoted mass transfer and increased the sensitivity of molecular physisorption of non-polar H2. The excellent transport properties resulting from such monolithic characteristics supported accurate detection of resistance changes.The concentrations of adsorbed H samples  and lowetrations . This sur effect , while hl groups . Combinisistance e. Conver centers e,f, in antration . Thus, iWe developed a novel 3D nanoporous rGO for molecular hydrogen detection at room temperature under gas flow conditions. The detection mechanisms of molecular hydrogen were revealed by using 3D nanoporous rGO specimens featuring a large surface area, a single bicontinuous monolithic sheet morphology, and unique transport properties (non-electron hopping conduction), and were found to be based on the charge transfer effect and Coulomb scattering effect. Moreover, DFT calculations revealed that hydroxyl, epoxide, ether, ketone, and carboxyl groups are preferable molecular physisorption sites, and that hydroxyl groups benefit from the sequential adsorption of molecular hydrogen. Nanoporous rGO with tunable oxygen-containing functional groups could provide a general platform for a room-temperature physisorption-type gas sensor and provide a new design direction for nanoporous material-based gas sensors for combustible gases.


Propionibacterium acnes-associated sarcoidosis complicated by acute bird-related HP.The number of reports on sarcoidosis complicated by hypersensitivity pneumonitis (HP) is limited, and most describe cases complicated by chronic bird-related HP. Here, we present for the first time a case with P. acnes lipoteichoic acid. Poorly formed non-caseating granulomas without positively stained substances were also detected.A 62-year-old man with a past medical history of sarcoidosis was admitted to our department, and chest computed tomography showed diffuse ground-glass opacities, which appeared as he rapidly increased the number of pigeons he kept for a competition. Random transbronchial lung biopsy revealed well-formed non-caseating epithelioid granulomas, which contained positively stained substances on immunohistochemistry using the PAB antibody, a specific monoclonal antibody against We describe the successful identification of this exceptionally rare case of sarcoidosis complicated by acute bird-related HP in which two morphologically and immunohistologically different types of granulomas were present in the same lung. Propionibacterium acnes, although infection with these organisms is only one of the possible suggested pathogenetic mechanism [P. acnes was recently renamed as Cutibacterium acnes, but we continue to use the earlier nomenclature to avoid confusion [P. acnes-associated sarcoidosis that have involved the detection of P. acnes in sarcoid granulomas [Granulomatous lung diseases are a heterogenous group of disorders that include both infectious and noninfectious conditions with a wide spectrum of pathologies and various clinical manifestations and outcomes. This makes differential diagnosis based on histopathological assessment challenging . Sarcoidechanism . Note thonfusion . Reporteanulomas –6. Sarcoanulomas .However, the number of reports on sarcoidosis complicated by HP is limited, and most describe cases of sarcoidosis complicated by chronic bird-related HP Table . SpecifiP. Acnes mAb (PAB antibody), a specific monoclonal antibody against P. acnes lipoteichoic acid [Here we report a case of sarcoidosis complicated by acute bird-related HP in which two distinct types of granuloma were successfully distinguished by immunohistochemistry (IHC) using anti-oic acid .A 62-year-old man who had cough and dyspnea on exertion for 3 months and weight loss of 3 kg in 6 months was admitted to our respiratory department in March 2017. He had a 28 pack-year smoking history and used a duvet for warmth in winter. Thirty years earlier, he had started breeding more than 300 pigeons for competition, and although the number had gradually decreased to about 30–40 birds in April 2016, he had then rapidly increased the number up to 130 in the year before admission  on chest X-ray Fig. a and comTrichosporon asahii were not detected. Using the ImmunoCAP assay , serum levels of IgG specific to pigeons, parrots, and budgerigars were determined to be ≥200 mgA/L , ≥ 200 mgA/L , and ≥ 200 mgA/L , respectively [CO) 15.33 mL/min/mmHg (%DLCO 75.8%).Chest X-ray Fig. c and CT ectively . The lymectively . Pulmona5/mL, lymphocytes 17%, and CD4/CD8 ratio 1.5. Random transbronchial lung biopsy revealed well-formed non-caseating epithelioid granulomas with clear margin, characteristic of sarcoidosis, in the right B4a bronchus. Additional IHC using PAB antibody [P. acnes-specific epitope of lipoteichoic acids, which contain a glycolipid moiety and are anchored in the cell membrane and penetrate through the cell wall. Immunostaining using this antibody can identify cell wall-deficient L-forms of P. acnes causing latent infection in granulomas [P. acnes was detected in granulomas in ≥80% of patients diagnosed with sarcoidosis, irrespective of the organs involved: both the sensitivity and specificity of PAB staining are high [In April 2017, BALF results were total cell count 17.0 × 10antibody  detectedanulomas . P. acneare high . At the Taken together with the fact that dyspnea, ground-glass opacities on chest CT, and elevated serum KL-6 level improved without medication during 2 weeks of hospitalization, he was diagnosed as having sarcoidosis complicated by acute bird-related HP. Pulmonary function test results improved to VC 4.93 L %VC 125.4%) and FEV1 3.22 L (%FEV1 101.3%). On discharge from the hospital, no medication was prescribed, but he immediately stopped keeping pigeons  gene, currently named PSMB, codes for subunits of the proteasome. This is a multimeric enzymatic complex that degrades proteins into peptides in order to be presented in the MHC class I pathway, and genetic polymorphism in LMP7 was reported to be associated with both sarcoidosis [Sarcoidosis and HP have, at least in part, common immunopathogenesis including T-helper type 1 (Th1)-type immune responses in which phagocytosed antigens by macrophages present with major histocompatibility complex (MHC) class II to induce the immune response . In the coidosis  and birdcoidosis . Howevercoidosis , the reaConcerning the first observation in this case that sarcoidosis was complicated by acute bird-related HP, the patient had an approximately 40-year history of keeping pigeons, and sarcoidosis with BHL was diagnosed 4 years before admission to our department. One year before admission, as the number of pigeons kept increased, he developed dyspnea on exertion with ground-glass opacities observed on chest CT, but these improved by avoiding exposure to culprit antigens during a hospital stay. Given that the patient tested positive for both serum IgG against bird-related antigens and LST using pigeon dropping extract, a diagnosis of acute bird-related HP complicated with sarcoidosis was made. Long-term bird-keepers become sensitized to bird-related antigens after long-term exposure, resulting in elevated levels of serum antibodies against these antigens. Such conditions pose risk of developing chronic bird-related HP, although not all individuals develop it. Similar to our case, there have also been cases reported of acute bird-related HP triggered by sudden increases in the number of birds kept . Also, bConcerning the second observation that two morphologically and immunohistologically different types of granulomas were present in the same lung, the limited number of reports on sarcoidosis complicated by HP may be attributed, at least in part, to difficulties in distinguishing their distinct granulomas. Sarcoid granulomas can be differentiated from HP granulomas by histopathology . Sarcoid granulomas are well-formed non-caseating epithelioid granulomas distributed along the lymphatic tracts  , 25, andIn conclusion, we have presented the first case of sarcoidosis complicated by acute bird-related HP in which two distinct types of granuloma were successfully distinguished by IHC using PAB antibody. Cases of sarcoidosis complicated by HP need to be accumulated with precise clinical evaluations reported to improve our understanding of this condition.


Chitosan nanofibrous membranes are prepared via an electrospinning technique and explored as potential wound healing patches. In particular, the effect of a physical or chemical crosslinking treatment on the mat morphological, mechanical, water-related, and biological properties is deeply evaluated. The use of phosphate ions  allows us to obtain smooth and highly homogenous nanofibers with an average size of 190 nm, whereas the use of ethylene glycol diglycidyl ether  leads to rougher, partially coalesced, and bigger nanofibers with an average dimension of 270 nm. Additionally, the physically crosslinked mats show enhanced mechanical performances, as well as greater water vapour permeability and hydrophilicity, with respect to the chemically crosslinked ones. Above all, cell adhesion and cytotoxicity experiments demonstrate that the use of phosphate ions as crosslinkers significantly improves the capability of chitosan mats to promote cell viability owing to their higher biocompatibility. Moreover, tuneable drug delivery properties are achieved for the physically crosslinked mats by a simple post-processing impregnation methodology, thereby indicating the possibility to enrich the prepared membranes with unique features. The results prove that the proposed approach may lead to the preparation of cheap, biocompatible, and efficient chitosan-based nanofibers for biomedical and pharmaceutical applications. Tissue reparation, which is a natural process, is often diminished by a broad number of factors with the employment of wound healing patches currently assuming a highly important role . Nowadayellulose . The exiellulose ,29,30. Hellulose ,32. Addiellulose . In thisellulose ,35.With these premises, in a previous work, the electrospinning of chitosan solutions was optimized by using poly(ethylene oxide) as a co-spinning agent, which was subsequently completely removed, and a physical or a chemical crosslinking treatment was specifically applied to enhance the fiber stability . Here, tv = 900 kDa, TritonTM X-100 laboratory-grade, glacial acetic acid, absolute ethanol (EtOH), ammonium hydroxide (NH4OH), sodium phosphate dibasic (Na2HPO4), and ethylene glycol diglycidyl ether (EGDE) ), thiazolyl blue tetrazolium bromide (MTT), and dimethyl-sulfoxide (DMSO) were purchased from Sigma Aldrich . Saos-2 human osteoblast cell line and mouse fibroblast L929 cell line were obtained from the American Type Culture Collection . Human keratinocyte HaCaT cell line  was obtained by the Cell Lines Service . DMEM cell medium, glutamine, Fetal Bovine Serum (FBS), penicillin/streptomycin antibiotic solution and ready-to-use trypsin solution were purchased from Microstech Srl . Tissue culture flasks and 96-well plates were purchased from VWR International .Low molecular weight chitosan was obtained from Sigma-Aldrich and used without further purification. A degree of deacetylation (DD) of 78% was estimated via a conductometric titration method . Poly, respectively. Then, the system was added with 1 wt% of Triton and maintained under gentle stirring for 24 h at room temperature and finally conserved at T = 4 °C.CS-PEO batch solution to be electrospun was prepared as previously reported . Firstly®  Professional Electrospinning Machine equipped with an aluminium flat collector was employed to electrospin the prepared chitosan-based solution. A detailed description of the fabrication procedure optimization is reported in a previously published work [4OH/H2O 7/2/1 at pH = 7.5, to neutralize the acetic acid and prevent the dissolution of chitosan in aqueous environments. The samples were then dried in an oven at T = 50 °C under vacuum overnight and subsequently immersed for 3 h in a crosslinking solution. Physically and chemically crosslinked membranes were prepared by using a 10 w/v% Na2HPO4 aqueous solution or a 2.5 v/v% EGDE aqueous solution heated up at T = 60 °C, respectively. Finally, chitosan-based mats were washed several times with deionized water and dried in an oven at T = 50 °C under vacuum overnight before being stored in a desiccator and characterized. It is noteworthy that chitosan chemical crosslinking was carried out at a temperature of 60 °C in order to accelerate the reaction hence reducing the loss of the nanofibrous structure.Doxa Microfluidicshed work . In a tyMembrane morphology was evaluated via field-emission scanning electron microscopy (FESEM) through ZEISS  SUPRA 40 VP operating at 10 kV in direct detector configuration (InLens). Good conductivity of the samples was assessed with a thin layer of sputter-coated carbon using a Polaron  E5100. ImageJ  open-source software was employed to analyse the nanofiber dimension. At least 200 diameter measurements were taken for each of the high-magnification micrographs.b), and the elongation at break (εb) were calculated from the obtained stress-deformation curves.Uniaxial tensile test was performed on the crosslinked mats by using a displacement-controlled dynamometer Instron 5565 . At least five rectangular specimens (40 × 10 mm) were tested for each sample. The thickness of the membranes was evaluated via a precision digital micrometer. A pre-load of 0.1 N and an elongation rate of 25 mm/min were employed for all the experiments. The Young modulus E, the tensile strength (σWater contact angle (WCA) of the crosslinked membranes was measured via an Attention Theta Lite optical tensiometer . A small drop of water  was placed on the sample surface and both right and left WCA were calculated via the instrument software.2) is the surface of the sample that permits the vapour diffusion, and ∆p (Pa) is the partial water vapour pressure difference across the two sides of the sample.Water vapour permeability (WVP) of the crosslinked membranes was assessed by means of a gravimetrical method according to ASTM E96-95. Briefly, circular samples were mounted on measuring cups with a diameter of 9.5 mm which were filled with distilled water up to 2 cm underneath the film. The cups were placed in an environmental chamber at 37 °C and 50% RH and weighted every hour for a period of 8 h. WVP was calculated as follows:i and Mf are the weights of the sample before and after the drying, respectively.The moisture content (MC) of the crosslinked membranes was determined by placing a small piece of each sample at T = 110 °C under vacuum for 24 h and evaluating the weight loss after the drying process. MC percentage on a wet-basis was expressed as:2 atmosphere in high glucose Dulbecco’s modified Eagle’s medium (DMEM), with glutamine supplemented wi th 10% FBS using penicillin/streptomycin as antibiotics. Experiments were performed in triplicate on 96-well plates. Crosslinked chitosan membranes were cut to obtain circular discs of 6 mm Ø and autoclaved before being positioned at the bottom of the wells.All cell lines were cultured at T = 37 °C in a humidified, 5% COTo evaluate the eventual cytotoxicity, crosslinked chitosan mats were soaked in complete cell medium and incubated in the 96-well plates with 100 μL of medium per well for 6 h at T = 37 °C. After the incubation with the membranes, the cell medium from each well was collected and added to 96-well plates containing the cell cultures  with a final dilution of the extracts of 1:1. After 24 h, cell viability was measured by the MTT test as already described .To evaluate cell adhesion on chitosan-based nanofibers, the cells were seeded at 10000 cells/well onto the membranes at T = 37 °C and incubated for 16 h. For each cell line, a standard curve was seeded in quadruplicate in the 96-wells in the 1250–10,000 cells/well range to obtain a linear regression curve to fit the experimental results and extrapolate the number of cells attached to the different membranes. At the end of the experiments, cell viability was assayed by MTT test as previously described . BrieflyData are the means ± S.D. of three independent experiments.Adsorption and desorption properties of the physically crosslinked electrospun mats were investigated by using methylene blue (MB) and methyl orange (MO) as model drug molecules of opposite charge. UV-vis absorption spectra were acquired utilizing a UV-1800 spectrophotometer  at room temperature.In a typical kinetic adsorption study, 5 mg of sample were placed within a fused silica cuvette with 1 cm pathlength and soaked with 3.5 mL of dye aqueous solution at a given concentration . The system was gently shaken for 6 h at room temperature and the solution dye concentration was periodically monitored.In a typical isotherm adsorption experiment, 5 mg of the membrane were immersed in 50 mL of dye solutions with increasing concentration  under gentle shaking for a week at room temperature and then the supernatant dye concentration was analysed.In a typical desorption experiment, a dye-loaded membrane was rapidly washed with EtOH and placed in a 1 cm pathlength fused silica cuvette. As the release medium, 3.5 mL of PBS at pH = 7.4 and T = 37 °C were used to simulate physiological conditions. The system was kept under gently stirring and the concentration of the supernatant was periodically monitored for 6 h.t), at equilibrium (qe), and the cumulative release percentage (R%) were determined as:0, Ct, Ce (mg/L) are the dye concentration at the initial time to, at a given time t and equilibrium, respectively, V (L) is the solution volume, M (g) is the weight of the membrane, mi (mg) is the dye load in the membrane at the time t0, and mr (mg) is the dye amount released at time t.The dye absorption capacity at a given time t  and smoother nanofibers that completely maintained their individuality, thereby leading to the formation of a high number of interconnected pores. On the contrary, the chemical crosslinking treatment promoted the partial coalescence of the nanofibers , which in turn led to the establishment of a denser nanostructure presenting an average low porosity. Such findings are, to some extent, unexpected but may be most likely ascribable to the dissimilar reticulation mechanism and kinetic. Indeed, chemical crosslinking occurs via the formation of strong, stable, and not reversible covalent bonds between chitosan chains, whereas HPOch other . In any ch other ,42.Mechanical and water-related properties play a fundamental role in most biomedical devices where the existence of applied stresses and the existence of interfaces with native tissues are not negligible. In particular, wound healing patches should present features similar to those of human tissues, at the same time providing integrity and stability to offer a sufficient protective capability towards the external environment ,44,45. Ib, and tensile strength σb) are summarized in Stress-deformation curves obtained for both physically and chemically crosslinked mats via uniaxial tensile test are reported in Unexpectedly, the physical crosslinking led to more mechanically performing mats despite its weaker crosslinking efficiency. Specifically, the Young modulus and tensile strength were almost twice those of the chemically crosslinked membranes, whereas a slighter difference was observed for the elongation at break. However, rather than directly to the mechanism involved in the chitosan reticulation, the obtained disparities are most likely ascribable to the sample morphology. Indeed, the greater nanofiber homogeneity achieved via physical crosslinking led to the development of a much more ordered three-dimensional macroscopic structure able to provide for the superior mechanical performances. Conversely, the coalescence of the nanofibers occurring during the chemical crosslinking induces the establishment of a defect-rich network characterized by an inferior response ,49.Another key factor concerning wound healing patches is represented by their water-related behaviour ,51. As aThe water contact angle, the water vapour permeability, and the moisture content values of both physically and chemically crosslinked chitosan-based mats are reported in First of all, a marked discrepancy between the hydrophilicity of the samples can be observed with the physically crosslinked mats showing a much lower WCA with respect to the chemically crosslinked ones. Such a result is related to both the crosslinking mechanism and nanofiber morphology. Chitosan, owing to the presence of residual acetyl groups, is characterized by a poor water solubility that is even lowered after the crosslinking approach. Therefore, the stronger the links between the macromolecular chains , the smaller is the capability of chitosan to interact with water . Additionally, the thinner and defect-free nanofibers achieved via physical crosslinking present a higher surface area, thereby endowing the mats with a higher porosity, which, in turn, leads to capillarity effects that can promote the water-material compatibility. Further evidence of this phenomenon can be derived from the water vapour permeability value, which is nearly an order of magnitude smaller for the chemically crosslinked mats. In this regard, the presence of a great number of interconnected pores and the marked hydrophilicity of mats obtained via physical crosslinking seem to provide a much higher water vapour permeability. Finally, both samples presented low moisture content, hence being suitable to be stored over quite long periods without occurring in degradation issues and/or physical-chemical modifications.Considering the above-discussed results, the physically crosslinked chitosan-based mats seem to be much more promising compared to the chemically crosslinked ones for the development of potential wound healing patches. Indeed, the achieved mechanical properties indicate that such systems could be able to endure considerable stresses and deformations before showing mechanical failure, thereby being suitable to provide a highly stable environment to foster cell viability in different types of wounds . In addition, the marked hydrophilicity coupled with the great water vapour permeability may promote the exudate removal and gas exchange, thereby maintaining the tissues dried at the same time providing appropriate breathability, which are both important factors in the regeneration process.Chitosan is a well-known biocompatible material  even if p < 0.05). The L929 fibroblasts (p < 0.05). This latter result might be related to the fact that these cells preferentially adhere to fibrin or collagen substrates of protein origin. Such molecules, indeed, mimic more closely the basal membrane to which keratinocytes naturally adhere at the interface between epidermis and dermis [All cell types showed a clear preference for the physically crosslinked membranes with respect to the chemical ones. More in detail, the osteoblast cell line, Saos-2 f, showedroblasts b showed roblasts d showed d dermis ; therefop < 0.0001 and p < 0.005, respectively). Conversely, only one cell line—namely, HaCaT keratinocytes reported in p < 0.0005). In contrast, no toxicity was observed in the L929 fibroblasts  are summarized in In detail, MB was scarcely adsorbed by the mats with the process being almost arrested after only 2 h for the studied experimental conditions. Conversely, MO was rapidly and much more efficiently entrapped within the electrospun membranes with the phenomenon evolving even after 6 h, especially for the highest dye concentration . To better understand the kinetics of adsorption, pseudo-first-order and pseudo-second-order models were employed to fit the experimental data ,56. Intee values, it can be supposed that strong repulsive interactions arise between chitosan chains and the colorant molecules. Therefore, the adsorption is most likely driven by diffusive phenomena but remains highly hindered due to the electrostatic repulsions. In this sense, since oxygen-containing groups were proved to be frequently involved in the adsorbate-adsorbent mechanisms, the hydroxyl substituents of chitosan are likewise supposed to provide functional sites for the uptake through hydrogen bonding [e values. Nevertheless, since the adsorption process continues over a certain period of time, it is most likely that both electrostatic and diffusive phenomena play here an important role.The results suggest that a different adsorption mechanism occurs for MB and MO dyes, which is in agreement with their different charge. Specifically, MB being positively charged and taking into account the low q bonding . ConversIn this sense, further confirmation was obtained by studying the isotherms of adsorption for both MB and MO dyes with the related results shown in Independently on the phenomena driving the dye upload, a much more interesting aspect is related to the membrane release capabilities that are of topical importance in the development of controlled drug delivery systems. Calculated data are reported in In addition, future studies will be required, the achieved results represent a promising starting point in the development of simple, cheap, and efficient drug delivery systems with modulable release kinetics. Indeed, despite negatively charged molecules presenting a higher affinity for chitosan-based nanofibers and positively charged ones showing a better-controlled release, depending on both the drug nature and loading concentration, it could be possible to obtain DDSs able to provide a burst or a slow-release to satisfy the specific requirements.In the present work, electrospun chitosan-based nanofibers were prepared and subsequently subjected to a physical or chemical crosslinking treatment by using phosphate ions or ethylene glycol diglycidyl ether, respectively. Remarkably, physically crosslinked membranes were proved to show a broad number of advantages with respect to the chemically crosslinked ones. In particular, the use of phosphate ions led to much thinner and homogenous nanofibers , which, in turn, provided a greater global porosity and an enhanced mechanical response, as well as more marked hydrophilicity and water vapour permeability. Above all, significant differences were depicted between the mats in terms of cell adhesion and cytotoxicity. In particular, the nanofibers treated with phosphate ions showed no toxicity towards the different tested cell lines along with the capability to strongly promote their adhesion and proliferation, especially for osteoblasts. Conversely, the chemically crosslinked mats were found to be toxic for keratinocyte and osteoblast cell lines, thereby being able to marginally foster cell viability most likely due to the release of some residual chemicals. Owing to the aforementioned findings, the physically crosslinked mats were then loaded with two dyes, which were used as model drug molecules, and their delivery properties were intensively evaluated. Interestingly, by simply changing the charge of the dyes, the mats were proved able to show a burst or a slow sustained release, hence being suitable for different routes of administration. In conclusion, the proposed physically crosslinked chitosan-based mats represent a potential class of innovative, cheap, and highly efficient materials to be used as advanced wound healing patches with tuneable drug delivery properties. However, it is noteworthy that further in vitro and in vivo experiments are required to open the way to their effective use in biomedical and pharmaceutical products. Among others, some critical points that must be soon addressed include the improvement of the fabrication procedure , a better understanding of the product biological response  and drug delivery properties, as well as the evaluation of the scaffold degradation kinetics in physiological conditions.


First of all, we would like to thank all the authors for their contribution and the editorial staff who enabled the achievement of this “Management of Sarcoidosis: Challenges and Solutions” Special Issue. This issue covers a selection of hot questions on sarcoidosis pathogenesis and on everyday clinical practice in sarcoidosis. This issue is more an impressionist view of sarcoidosis than an exhaustive one, as significant progress was made both in the understanding of the pathogenesis and in diagnostic and therapeutic approaches—particularly in terms of changes in new concepts concerning genetics and auto-immunity, and a more comprehensive approach to the care. Therefore, the issue contains very didactic and practical general reviews, as well as original articles focused on little-known or mutating topics.Sarcoidosis is a disease with a large phenotypic variability due to the complex combination of genetic susceptibility, immune networks and still unknown infectious and/or environmental causal agents. Mycobacterium tuberculosis (PPD)-coated polystyrene beads. This model makes it possible to have access to the initial cellular and molecular events in granuloma formation [One way to penetrate the still opaque world of this systemic disease is in the development of selected models with a high level of confidence, which is Besnard and Jeny’s review’s objective . As theyormation . The secormation . As a coormation ,6. The tormation . Consecuormation . If the ormation . Of the ormation .Thanks to the development and mastery of innovative tools, significant pieces of genetics in the sarcoidosis jigsaw puzzle are added on a regular basis, which is clearly and extensively described by Calender et al. . A recenMycobacteroides abscessus or other bacteria. This noteworthy contribution from Baerlecken et al. reinforces the discussion about the classification of sarcoidosis among the vast spectrum of immune or inflammatory systemic diseases, which has always been a puzzle—immune granulomatous disease , auto-inflammatory disease (inflammasome activation) or auto-immune disease  [Autoimmunity features observed in sarcoidosis have been observed for a long time, but they raise the hypothesis of an underlying autoimmune disease that co-occurs with sarcoidosis , or a rontigens) ? Or, clontigens) ,22? To end with the pathogenic domain of the issue, McClain Caldwell et al. contributed a research paper opening a new field in sarcoidosis treatment, focused on the potential benefits of stem-cell therapy . It shouIn the area of clinical knowledge of sarcoidosis, classical reviews are still not outdated ,28,29. HJain et al. underscored the difficulty of the diagnosis, with often a significant delay, and most encounter comorbidities . Concern18FFDG-PET is a very efficient biomarker for determining treatable inflammatory lesions in symptomatic patients, particularly those with normal serological inflammation, like serum angiotensin-converting enzyme and serum sIL2R [18FFDG-PET has been indicated in three clinical contexts concerning patients with confirmed sarcoidosis, as follows: (i) patients with pulmonary fibrosis, for whom the expected beneficial treatment effect on Forced Vital Capacity can be predicted thanks to lung inflammation assessed by lung FDG uptake; (ii) patients with cardiac sarcoidosis for whom, subject to the patients’ diet before 18FFDG-PET being correct, a left ventricular ejection fraction gain under treatment might be expected thanks to cardiac FDG uptake; and (iii) patients with persistent disabling symptoms. Otherwise, for patients with suspected extrapulmonary sarcoidosis difficult to diagnose, such as isolated uveitis of unknown cause, central nervous system or cardiac manifestations with normal thorax CT, the evidence of 18FFDG uptake in both hilar and mediastinal lymph-nodes can usefully guide the diagnosis. As underscored by Keijsers, um sIL2R . 18FFDG-Advanced pulmonary sarcoidosis is the main cause of dangerous sarcoidosis. In their paper, Sawahata et al. had the original idea of comparing the thorax CT in patients with supplemental oxygen need with a previous one done several years before for a better understanding of the radiological findings’ significance . They prPediatric sarcoidosis is an extremely rare disease with a 0.6–1.02/100,000 estimated incidence, but in the absence of international registers, the disease is probably under-reported ,44. ChauEvidencing non-caseating granulomas on histopathology is very important for diagnosing sarcoidosis. Despite many original articles and reviews focusing on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS), the particularly well-written paper by Pedro et al. offers a means of getting very clear and accurate data concerning the advantages and the pitfalls of every endoscopic technique in sarcoidosis, and the impacts of many technical factors . EBUS haIn conclusion, while all the numerous questions raised by sarcoidosis could not have been included in the register of this Special Issue, such as for example the potential role of the microbiota in sarcoidosis , or a ne