Laurence Dangers

Jonathan Giovannelli

MD Gilles Mangiapan

MD Mikael Alves

MD Naïke Bigé

MD, PhD Jonathan Messika

MD PhD Elise Morawiec

MD Mathilde Neuville

MD Christophe Cracco

MD Gaëtan Béduneau

MD Nicolas Terzi

MD Isabelle Huet

MD Xavier Dhalluin

MD Nathalie Bautin

MD Jean-Jacques Quiot

MD Corinne Appere-De Vecchi

MD Thomas Similowski

MD Cécile Chenivesse
email: cecile.chenivesse@chru-lille.fr

Antiplatelet Drugs and Risk of Bleeding After Bedside Pleural Procedures

Keywords: antiplatelet drug, bleeding risk, pleural procedure, thoracentesis, chest tube insertion, closed pleural biopsy

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Introduction

Pleural disorders affect over 3000 people per million population each year in developed countries [START_REF] Rand | Introduction and methods: British Thoracic Society Pleural Disease Guideline[END_REF], caused by a wide range of pathologies, in particular congestive heart failure, infection, and cancer. Pleural procedures (thoracentesis, closed pleural biopsy, or chest tube insertion) are key to diagnosis [START_REF] Maskell | British Thoracic Society Pleural Disease Guidelines--2010 update[END_REF] and may also be the main therapeutic approach in conditions such as pneumothorax [START_REF] Macduff | Management of spontaneous pneumothorax: British Thoracic Society Pleural Disease Guideline 2010[END_REF]. All of these procedures entail a risk of bleeding, which is infrequent but may be life-threatening [START_REF] Hooper | Pleural procedures and patient safety: a national BTS audit of practice[END_REF]. Patients taking concomitant antiplatelet drugs would usually be considered at higher risk for this complication, raising the question antiplatelet therapy discontinuation before pleural procedures. However, withdrawing antiplatelet drugs may have adverse consequences in patients with coronary [START_REF] Charlot | Clopidogrel discontinuation after myocardial infarction and risk of thrombosis: a nationwide cohort study[END_REF] or cerebral [START_REF] Sibon | Antiplatelet drug discontinuation is a risk factor for ischemic stroke[END_REF] vascular diseases at high risk of thrombosis. Long-term antiplatelet therapy is now commonly prescribed and the risk of thrombosis after their withdrawal well known. In contrast, data on the risk of post-pleural procedure bleeding associated with antiplatelet therapy are scant. Previous studies have reported low rates of hemorrhagic complications after pleural procedures in patients receiving antiplatelet therapy. However, they were single-center studies and included few patients [START_REF] Zalt | Effect of routine clopidogrel use on bleeding complications after ultrasound-guided thoracentesis[END_REF] [START_REF] Dammert | Safety of ultrasound-guided small-bore chest tube insertion in patients on clopidogrel[END_REF] [START_REF] Mahmood | Hemorrhagic complications of thoracentesis and small-bore chest tube placement in patients taking clopidogrel[END_REF], in particular the size of study populations was below the number of procedures necessary to observe even one bleeding event after pleural procedures. In other areas, the increased risk of bleeding in patients receiving antiplatelet drugs after chest surgery, bronchoscopy, or interventional pulmonary procedures is well established and has led to guidelines on the management of antiplatelet drugs before procedures [START_REF] Ferraris | update to the Society of Thoracic Surgeons guideline on use of antiplatelet drugs in patients having cardiac and noncardiac operations[END_REF] [START_REF] Trosini-Désert | Fibreoptic bronchoscopy and anti-platelet agents: a riskbenefit analysis[END_REF] [START_REF] Ernst | Interventional pulmonary procedures: Guidelines from the American College of Chest Physicians[END_REF]. In contrast, the current international guidelines for pleural procedures do not address the question of antiplatelet drug management (2) [START_REF] Havelock | Pleural procedures and thoracic ultrasound: British Thoracic Society Pleural Disease Guideline 2010[END_REF]. The general guidance on all percutaneous procedures in patients taking antiplatelet drugs noted that its recommendations for pleural procedures were limited due to the weakness of available data [START_REF] Baron | Management of antithrombotic therapy in patients undergoing invasive procedures[END_REF]. In consequence, clinical decision making is heterogeneous [START_REF] Dangers | Pleural procedures in patients treated by platelet aggregation inhibitors: An opinion survey[END_REF] and patient safety potentially compromised.

The current study was conceived to assess the risk of bleeding and serious bleeding associated with antiplatelet drugs in patients undergoing pleural procedures.

Methods

Setting and patients

We conducted a multicenter cohort study involving 19 French centers (eight respiratory care departments and 11 intensive care units in 14 university teaching hospitals and five general hospitals). All patients undergoing bedside thoracentesis, closed pleural biopsy or chest tube insertion from November 2011 to January 2014 were considered for inclusion. We excluded patients aged less than 18, those with hemothorax, recent chest surgery, receiving full anticoagulation or under extracorporeal membrane oxygenation. Participants were considered to be in the exposed (or antiplatelet) group if they were receiving antiplatelet drugs at the time of the procedure and at least five days before the procedure. They were considered to be in the unexposed (or control) group if they had never been under antiplatelet therapy or were free from antiplatelet drugs during at least five days before the pleural procedure [START_REF] Patrono | Antiplatelet drugs*: American college of chest physicians evidencebased clinical practice guidelines (8th edition)[END_REF] [START_REF] Gogarten | Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology[END_REF] (18) [START_REF] Godier | Management of antiplatelet therapy in patients undergoing elective invasive procedures[END_REF]. To avoid confusion regarding the evaluation of bleeding risk, patients in whom antiplatelet drugs had been interrupted for any reason during the five days preceding the pleural procedure were not included in the study.

The study was approved by the Institutional Review Board of the French Language Respiratory Society (Société de Pneumologie de Langue Française, CEPRO 2011-051) and was declared to the National Commission on Informatics and Liberty (CNIL 911367). Study informations were included in an information booklet routinely given to all patients prior to thoracentesis, closed pleural biopsy or chest tube insertion during the study period. French legislation on noninterventional studies requires collecting non-opposition of patients but does not require written consent. As such, non-opposition was obtained from each patient included in the study for the use of their deidentified medical records data. Participants did not receive financial compensation.

Outcomes

The main outcome was the occurrence of "bleeding", defined as the occurrence of hematoma, hemoptysis or hemothorax, during the 24 hours following the pleural procedure. The secondary outcome was the occurrence of "serious bleeding" during the 24 hours post pleural procedure, defined as bleeding requiring blood transfusion, respiratory support, endotracheal intubation, embolization or surgery, or when death occurred. In the event of bleeding, the interventions required (follow-up, blood transfusion, respiratory support, endotracheal intubation, embolization or surgery) were recorded, as was the occurrence of death.

Other measurements and risk factor for bleeding

We documented demographic (age, gender, body mass index) and biological data (platelets count, prothrombin time (PT), activated partial thromboplastin time (APTT) ratio, creatinine clearance, measured the day or the day before the procedure), as well as procedure characteristics (operator experience, diameter of pleural device, and radiographic guidance). Radiographic guidance included both ultrasonographic and Computed Tomography (CT) scan guidance, the latter one consisting in marking the puncture site using a felt tip pen during a chest CT scan; then, pleural procedure was performed at bedside without real-time guidance. We determined risk factors for bleeding for each patient. Intrinsic risk factors for bleeding were defined as age > 65 years, platelet count < 100 10 9 /L, PT < 50%, APTT > 1.4, and moderate and severe renal failure (creatinine clearance < 60 and 30 L.min -1 as assessed with Cockcroft-Gault formula (2)(12)( 13)). Extrinsic risk factors for bleeding were defined as junior operator (resident or medical student), experience of operator < 50 procedures, no image-guidance for pleural procedure, and pleural device diameter > 14F.

Statistical analysis

Study group characteristics were described using mean ± standard deviation, or median ± interquartile range in case of non-normality, for quantitative variables and number (percentage) for qualitative variables.

Comparison between groups was performed using Student's t-test, or Wilcoxon tests in case of nonnormality, for quantitative variables and Fisher exact tests for qualitative variables. The 24-hour incidence of bleeding (and serious bleeding) was calculated in the whole population, in the exposed to antiplatelet therapies group and in the control group. Because the number of events was low, the 95% confidence intervals (CI) were computed using a bias-corrected accelerated bootstrap method with 10,000 replications [START_REF] Efron | Estimation and Accuracy after Model Selection[END_REF].

To assess the association between bleeding events, as the dependent variable, and antiplatelet drugs as the explanatory variable, we first conducted univariate analyses using univariate logistic regression. The main logistic multivariate model was constructed considering baseline characteristics for adjustment: (i) excluding the collinear covariates (highly associated each other, e.g. pleural procedure and pleural device diameter); (ii) choosing the covariates most associated with the dependent variable in univariate analysis when the quantitative or qualitative covariate was available (e.g. PT); and (iii) assessing the linearity between the dependent variable and quantitative covariates using cubic splines in adjusted generalized additive models. The main model was then adjusted for gender, age, platelet count, PT, APTT ratio, moderate renal failure, department, pleural procedure, operator experience and radiographic guidance.

Because the number of events was small relative to the number of covariates, we have taken care to verify the convergence of the model (control of the number of iterations, stability of the coefficients and standard errors during the successive addition of the covariates). Interaction terms between antiplatelet drugs and the covariates were tested one at a time in multivariate logistic models. In addition, we conducted sensitivity analyses: (i) using a backward stepwise selection; and (ii) using the Firth's bias-Reduced penalized-likelihood logistic regression adapted to rare events [START_REF] Firth | Bias Reduction of Maximum Likelihood Estimates[END_REF], adjusted for the same covariates that within the main model. Finally, to assess the center effect, we added the center as a random-effect in a univariate generalized linear mixed-effects model; adjustments were not possible because of problems of convergence of the model. Results were expressed as odds ratios (OR) with 95% confidence interval (CI).

Given the rarity of the events, the association between serious bleeding events and antiplatelet drugs was study using a univariate logistic regression, and a multivariate analysis only adjusted for the number of total (intrinsic and extrinsic) bleeding risk factors per patient.

All statistical analyses were performed using R software, version 3.5.2 [START_REF]R: A language and environment for statistical computing[END_REF]. The threshold for statistical 1 significance was 0.05.

2

Results

Patients and procedures

The study population consisted of 1124 patients, 737 (66%) men and 387 (34%) women, whose median age was 62.6 ± 27.7 years. Among them, 182 were taking antiplatelet drugs (142 treated by aspirin, 17 by clopidogrel, 22 by aspirin and clopidogrel, and one by aspirin and prasugrel), and 942 were not. Pleural procedures consisted of 377 thoracenteses, 130 closed pleural biopsies and 617 chest tube insertions (including 343 surgical and 270 percutaneous chest tube insertions; four missing values). The procedure was indicated for pleural effusion in 80% and pneumothorax in 20% of the whole population (Table 1).

Patients taking antiplatelet drugs were more likely to be men (73% vs 64%, p=0.028) and older (76% vs 39% over 65 years, p<0.001), and to have a higher body mass index (24.4 ± 6.5 vs 22.7 ± 5.7 kg.m -2 , p<0.001) and a poorer renal function (50% vs 27% for moderate renal failure, p<0.001). They were less likely to have thrombopenia (2% vs 8%, p=0.004). Differences in PT and APTT ratio between groups did not reach significance. The indication for pleural effusion was higher in the antiplatelet group (89% vs 78%, p<0.001).

In the antiplatelet group, the rate of image-guidance was higher (77% vs 68%, p=0.01). The rate of image guidance was significantly higher when pleural procedure was performed for pleural effusion than for pneumothorax (82% vs 21%, p<0.001). Among the 781 patients having radiologic guidance, 689 were ultrasonographic guidance and 92 were CT scan guidance. We did not observe significant difference between groups for operator experience and pleural device diameter (Table 1). The kind of pleural procedure was highly associated with the indication (p<10 -9 ) and the pleural device diameter (p<10 -9 ).

Likewise, the experience of the operator was highly associated with the senior or junior doctor status (p<10 -9 ).

Description of bleeding events

Fifteen bleeding events occurred, six in the antiplatelet group and nine in the control group, including nine hemothorax, two hemoptysis, and three hematomas. In one case, the nature of the bleeding event was not documented in the electronic form. Nine events occurred after chest tube insertion (two after surgical and six after percutaneous chest tube insertions (p=0.15); one missing value), five after thoracentesis and one after closed pleural biopsy. It means that 1.5% of chest tube insertions, 1.3% of thoracenteses and 0.8% of closed pleural biopsies led to bleeding (p>0.99). The 24-hour incidence of bleeding was 1.33% (95% CI, 0.71 to 2.05) in the whole population, 3.23% (95% CI, 1.08 to 5.91) in the antiplatelet group and 0.96% (95% CI, 0.43 to 1.60) in the control group. In the antiplatelet group, all bleeding events occurred in patients taking aspirin monotherapy.

Eight serious bleeding events occurred, five in the antiplatelet group and three in the control group.

Overall, 83.3% of bleeding events occurring in patients on antiplatelet therapy were serious vs 33.3% in controls. No death occurred. Five serious bleeding events occurred after chest tube insertion, two after thoracentesis, and one after closed pleural biopsy. In other terms, 0.8% of chest tube insertions, 0.5% of thoracenteses and 0.8% of closed pleural biopsies led to serious bleeding (p = 0.89). The 24-hour incidence of serious bleeding was 0.71% (95% CI, 0.27 to 1.25) in the overall study group, 2.69% (95% CI, 0.54 to 5.38) in the antiplatelet group and 0.32% (95% CI, 0 to 0.75) in the control group.

Association between bleeding events and antiplatelet therapy

In univariate analysis, the occurrence of bleeding events was significantly associated with antiplatelet therapy (OR, 3.44; 95% CI, 1.14 to 9.66; p=0.021). It was also significantly associated with platelet count (OR, 0.44; 95% CI, 0.25 to 0.73 per 100 G.L-1 increase; p=0.002), PT level (OR, 0.76; 95% CI, 0.61 to 0.97 per 10% increase; p=0.020), APTT ratio (OR, 3.18; 95% CI, 1.26 to 6.81 per one unit increase; p=0.006), increased APTT ratio > 1.4 (OR, 3.28; 95% CI, 1.01 to 9.39; p=0.033), and severe renal failure (OR, 4.68; 95% CI, 1.01 to 16.60; p=0.025) (Table 2). In multivariate analysis, after adjusting for gender, age, platelet count, PT, APTT ratio, moderate renal failure, department, pleural procedure, operator experience and radiographic guidance, the occurrence of bleeding events was significantly associated with antiplatelet therapy (OR, 4.13; 95% CI, 1.01 to 17.03; p=0.044) (Table 2). The analysis showed no significant interaction of any covariable with antiplatelet therapy (data not shown). In sensitivity analyses, we also observed an association between the occurrence of bleeding events and antiplatelet therapy using (i) the stepwise procedure (OR, 5.16; 95% CI, 1.41 to 18.36; p=0.010) (Table 2); and (ii) the Firth's bias-Reduced penalizedlikelihood logistic regression (OR, 4.02; 95% CI, 2.62 to 8.44). Finally, the univariate association between the occurrence of bleeding and antiplatelet therapy was similar and remained significant when adding the center as a random-effect (OR, 3.40; 95% CI, 1.11 to 9.72; p=0.024).

Likewise, antiplatelet therapy was significantly associated with the risk of serious bleeding (OR, 8.61; 95% CI, 2.09 to 42.3; p=0.003) in univariate analysis. This association remained statistically significant after adjustment for the number of bleeding risk factors per patient (OR, 7.27; 95% CI, 1.18 to 56.1; p=0.032).

Discussion

In our study, antiplatelet therapy was identified as an independent risk factor for post-pleural procedure bleeding (OR, 4.13; 95% CI, 1.01 to 17.03; after adjustment for the main risk factors of bleeding) and serious bleeding (OR, 7.27; 95% CI, 1.18 to 56.1; p=0.032; after adjustment for the number of risk factors of bleeding). These findings are the first to firmly demonstrate the relationship between antiplatelet therapy and post-pleural procedures bleeding events and to give an estimation of the rate of bleedings in patients taking antiplatelet therapy at the time of the procedure. They are consistent with a previous study, which reported one case of severe hemothorax after thoracentesis among twenty-five patients treated with clopidogrel while none of the fifty controls experienced bleeding [START_REF] Mahmood | Hemorrhagic complications of thoracentesis and small-bore chest tube placement in patients taking clopidogrel[END_REF]. In contrast, two other studies, limited by small study sample and design, did not find any significant bleeding after pleural procedure in patients taking antiplatelet therapy [START_REF] Zalt | Effect of routine clopidogrel use on bleeding complications after ultrasound-guided thoracentesis[END_REF] [START_REF] Dammert | Safety of ultrasound-guided small-bore chest tube insertion in patients on clopidogrel[END_REF].

Overall, antiplatelet therapy is associated with an increased risk of bleeding and blood product usage after all kinds of surgery [START_REF] Ferraris | update to the Society of Thoracic Surgeons guideline on use of antiplatelet drugs in patients having cardiac and noncardiac operations[END_REF]. In the pulmonary interventional field, Ernst and al. reported in a prospective cohort study of 604 patients undergoing transbronchial lung biopsy, including 30 patients on clopidogrel, that the rate of bleeding was dramatically increased in patients taking clopidogrel (88% vs 3.4% in controls, including 34% of moderate and 27% of major bleeding) [START_REF] Ernst | Effect of routine clopidogrel use on bleeding complications after transbronchial biopsy in humans[END_REF]. In contrast, in a large retrospective analysis of 15,181 percutaneous core biopsies, including 1,174 lung biopsies, Atwell and al. reported a similar rate of bleeding in patients taking aspirin (0.6%, n=3,195) and controls (0.4%, n=11,986; p=0.34) [START_REF] Atwell | Incidence of bleeding after 15,181 percutaneous biopsies and the role of aspirin[END_REF]. However, this later study was highly limited by the definition of aspirin use based on the ingestion of aspirin within the 10 days preceding the biopsy but not specifically at the time of the procedure.

The risk of bleeding following a percutaneous procedure is arbitrarily classified as high when the rate of bleeding is over 1.5% in the general population or when they are performed in vital organs [START_REF] Baron | Management of antithrombotic therapy in patients undergoing invasive procedures[END_REF]. In our study, we found a low rate of bleeding after pleural procedure in the overall study population, evaluated at 1.33% (95% CI, 0.71 to 2.05). Previous studies have reported variable rates of post-pleural procedures bleeding ranging from 0 to 3.8% for thoracentesis [START_REF] Spanuchart | Hemothorax after thoracentesis[END_REF] [START_REF] Jones | Ultrasound-Guided Thoracentesis: Is It a Safer Method[END_REF] [START_REF] Colt | Evaluation of patient-related and procedure-related factors contributing to pneumothorax following thoracentesis[END_REF] [START_REF] Grogan | Complications associated with thoracentesis. A prospective, randomized study comparing three different methods[END_REF], 0 to 12.5% for closed pleural biopsy (2)(29)(30) [START_REF] Morrone | Pleural biopsy with Cope and Abrams needles[END_REF], and 0 and 4.2% for chest tube insertion [START_REF] Cho | Management of primary and secondary pneumothorax using a small-bore thoracic catheter[END_REF] [START_REF] Horsley | Efficacy and complications of small-bore, wire-guided chest drains[END_REF] [START_REF] Marquette | Simplified stepwise management of primary spontaneous pneumothorax: a pilot study[END_REF]. These studies were not designed to specifically address the question of hemorrhagic complications related to pleural procedures and they predate the publication of guidelines for pleural procedures (2) [START_REF] Havelock | Pleural procedures and thoracic ultrasound: British Thoracic Society Pleural Disease Guideline 2010[END_REF]. A more recent audit conducted in the United Kingdom found results similar to ours with 1.1% of hemothorax and 1% of chest wall hematomas among 1162 thoracenteses, and 1.3% iatrogenic hemothorax among 1394 chest tube insertions [START_REF] Hooper | Pleural procedures and patient safety: a national BTS audit of practice[END_REF]. In this study, the impact of antiplatelet therapy on bleeding events was not analyzed. Although hemorrhagic complications of pleural procedures were infrequent in the UK study and ours, they can be life-threatening.

In our study, we found a rate of severe bleeding at 0.71% (95% CI, 0.27 to 1.25) in the overall population.

Fortunately, there were no deaths among our patients, however post-pleural hemorrhagic complications are known to be possibly fatal [START_REF] Hooper | Pleural procedures and patient safety: a national BTS audit of practice[END_REF]. The rate of bleeding might have been lower if all the patients had received radiological guidance, as recommended (4). Indeed, we observed that only 69% of the procedures were realized under radiologic guidance. However, at the beginning of the study, the BTS guidelines were relatively recent and we hypothesize that practices in the centers involved in this study had not been modified yet. One patient with severe bleeding in the antiplatelet group had no radiologic guidance.

Altogether, these data suggest that antiplatelet therapy should be systematically stepped down to the minimum acceptable relative to the patient's thrombotic risk before any pleural procedure is undertaken.

These results are of particular importance since they represent a change to current practice in pulmonology [START_REF] Dangers | Pleural procedures in patients treated by platelet aggregation inhibitors: An opinion survey[END_REF].

Our study was not designed to evaluate the risk of thrombosis in patients who had stopped antiplatelet therapy for the procedure. However, we know from previous studies that, in patients at high risk of thrombosis, discontinuation of antiplatelet therapy is an independent predictor of death, transient ischemic attack, and acute coronary syndromes (35)(36)(37)(38) [START_REF] Rodríguez | Discontinuation of low dose aspirin and risk of myocardial infarction: case-control study in UK primary care[END_REF]. In our study, we found a frequency of bleeding at 3.23% (95% CI, 1.08 to 5.91) and of severe bleeding at 2.69% (95% CI, 0.54 to 5.38) in patients undergoing pleural procedures while receiving antiplatelet therapy; and none led to death. This risk may be considered as acceptable when balanced with the risk of a serious cardiovascular event associated with antiplatelet drug withdrawal in patients at high risk of thrombosis. If pleural procedures must be performed under antiplatelet therapy, a personalized approach should be performed including a comprehensive bleeding risk assessment, correction of all additional risk factors for bleeding and a particular attention to all aspects of the technique.

The main limit of the study is the presence of missing data, especially concerning renal function. In addition, the low number of events limited the multivariate analysis. However, we could construct a converging multiple linear model adjusted for the main risk factors of bleeding. Furthermore, this low number of events resulted in low statistical power that possibly explained that usual risk factors for bleeding were not associated with bleeding in the multivariate model. In addition, our study was not design to evaluate the risk of bleeding according to the antiplatelet agent. All bleedings occurred in patients treated by aspirin in monotherapy. No extra precautions were taken in patients receiving dual antiplatelet therapy, the absence of bleeding was probably due to the small number of patients in this group. Doses of aspirin were not recorded but supposed to be low (between 75 mg to 160mg per day) according to the French guidelines that recommend low doses of aspirin in cardiovascular diseases. Finally, our study pertains to bedside procedures only; the corresponding observations and interpretation cannot be extrapolated to CT-guided or surgical procedures.

Conclusion

Antiplatelet therapy was associated with an increased risk of post-pleural procedure bleeding and serious bleeding that should be taken into account in the benefice/risk balance when considering a pleural 13 procedure in a patient taking antiplatelet drugs. However, the rates of bleeding and severe bleeding were low, advocating that pleural procedures may be performed with an acceptable risk when antiplatelet therapy cannot be interrupted.

Acknowledgements

interest. Gaëtan Béduneau declares intervention fees from Dräger, and congress support from Hill-Rom and MSD. Nicolas Terzi declares congress support from Air Liquide and intervention fees from Pfizer and Boëhringer Ingelheim. Isabelle Huet reports personal fees from Menarini, AVAD, Boehringer Ingelheim congress support from SOS Oxygène, ISIS and Homeair. Xavier Dhalluin declares no conflict of interest. Nathalie Bautin declares intervention fees from AstraZeneca and congress support from Chiesi, AstraZeneca, Teva, Boeringer, SOS oxygène, Santelys, Elia Medical. , grants from Air Liquide Medical Systems, outside the submitted work. Cécile Chenivesse reports interventions, expertise, grants or congress support from ALK-Abello, AstraZeneca,

Authors' role

Laurence Dangers contributed to the conception and design of the work and to the acquisition, analysis and interpretation of data, drafted the work, and approved the final version of the manuscript.

Jonathan Giovannelli performed the statistical analysis, contributed to the analysis and interpretation of data, drafted the work, and approved the final version of the manuscript.

Gilles Mangiapan contributed to the acquisition and interpretation of data, revised the work critically for important intellectual content, and approved the final version of the manuscript.

Mikael


Yannick Bleu

Florent Bourquard

Jean-Yves Michalon

Y Lefkir

S Reynaud

Anne-Sophie Loir

Vincent Barnier

Florence Garrelie

Christophe Donnet

Transfer-Free Graphene Synthesis by Nickel Catalyst Dewetting Using Rapid Thermal Annealing

We report the transformation of amorphous carbon deposited by pulsed laser deposition (PLD) into free transfer graphene, associated with dewetting of the nickel catalyst film during rapid thermal annealing. Prior to graphene synthesis, dewetting of the pure nickel film is investigated versus thickness and temperature. Then a parametric study of graphene synthesis from an amorphous carbon film 2 nm thick is carried out by varying the starting thickness of the nickel catalyst (25, 50, 150 nm) at a temperature of 900°C. The graphene layers form on the top surface of the nickel film and at the interface between the nickel film and the SiO2 substrate, due to rapid diffusion of C through the Ni film. The concomitant nickel dewetting process enables exposure of the interfacial graphene while some graphene layers agglomerate on nickel particles. By removing the nickel particles with an acid treatment, interfacial graphene (also called free transfer graphene) was formed directly on the SiO2 substrate, avoiding a time consuming and relatively complicated transfer process. This work paves the way for the control of the number of layers of free transfer graphene using a solid carbon source and a nickel film catalyst.

Introduction

Research on graphene has received a lot of interest in recent years due to its outstanding physical and chemical properties, and its potential use in various applications [START_REF] Geim | The rise of graphene[END_REF][START_REF] Novoselov | Electric Field Effect in Atomically Thin Carbon Films[END_REF][START_REF] Nair | Fine Structure Constant Defines Visual Transparency of Graphene[END_REF][START_REF] Kim | Focused-Laser-Enabled p-n Junctions in Graphene Field-Effect Transistors[END_REF][START_REF] Bonaccorso | Graphene photonics and optoelectronics[END_REF]. For this reason, a variety of graphene synthesis techniques have been developed including mechanical exfoliation, annealing of SiC under ultrahigh vacuum, chemical vapor deposition (CVD), reduction of graphene oxide, and physical vapor deposition (PVD) [START_REF] Emtsev | Towards wafer-size graphene layers by atmospheric pressure graphitization of silicon carbide[END_REF][START_REF] Li | Graphene Films with Large Domain Size by a Two-Step Chemical Vapor Deposition Process[END_REF][START_REF] Hawaldar | Large-area high-throughput synthesis of monolayer graphene sheet by Hot Filament Thermal Chemical Vapor Deposition[END_REF][START_REF] Pei | The reduction of graphene oxide[END_REF]. Among PVD, pulsed laser deposition (PLD) is one of the alternative routes to CVD, the latter being the most commonly used process. As highlighted in our recent review paper related to the synthesis of graphene by PLD [START_REF] Bleu | Review of Graphene Growth From a Solid Carbon Source by Pulsed Laser Deposition (PLD)[END_REF], one of the main advantages of this process is that it allows precise 2 control of the thickness and composition of the carbon-based film (including the incorporated dopants) which acts as the solid-state precursor of the graphene layers. Several catalysts including nickel, copper, cobalt, copper-nickel alloy catalyst [START_REF] Reina | Growth of large-area single-and Bi-layer graphene by controlled carbon precipitation on polycrystalline Ni surfaces[END_REF][START_REF] Delamoreanu | Wafer scale catalytic growth of graphene on nickel by solid carbon source[END_REF][START_REF] Abd Elhamid | Study of graphene growth on copper foil by pulsed laser deposition at reduced temperature[END_REF][START_REF] Narula | Copper induced synthesis of graphene using amorphous carbon[END_REF][START_REF] Tyagi | Characterization of graphene films grown on CuNi foil substrates[END_REF][START_REF] Orofeo | Synthesis of large area, homogeneous, single layer graphene films by annealing amorphous carbon on Co and Ni[END_REF] have been suggested to convert the amorphous carbon film into graphene layers. Several studies have been published on the growth of graphene by PLD using a nickel catalyst [10, [START_REF] Tite | Graphene-based textured surface by pulsed laser deposition as a robust platform for surface enhanced Raman scattering applications[END_REF][START_REF] Fortgang | Robust Electrografting on Self-Organized 3D Graphene Electrodes[END_REF][START_REF] Maddi | Nano-Architecture of nitrogen-doped graphene films synthesized from a solid CN source[END_REF][START_REF] Koh | Comparison of the mechanism of low defect few-layer graphene fabricated on different metals by pulsed laser deposition[END_REF][START_REF] Bleu | Raman study of the substrate influence on graphene synthesis using a solid carbon source via rapid thermal annealing[END_REF][START_REF] Zhang | Fabrication and characterization of few-layer graphene[END_REF][START_REF] Bleu | Boron-doped graphene synthesis by pulsed laser co-deposition of carbon and boron[END_REF][START_REF] Bourquard | Electroanalytical Performance of Nitrogen-Doped Graphene Films Processed in One Step by Pulsed Laser Deposition Directly Coupled with Thermal Annealing[END_REF][START_REF] Bleu | Dynamics of carbon diffusion and segregation through nickel catalyst, investigated by in-situ XPS, during the growth of nitrogen-doped graphene[END_REF]. Schematically, thermal heating induces a dissolution of carbon atoms which diffuse into the metallic catalyst. During the thermal treatment and cooling process, the carbon solubility decreases and carbon segregates as graphene layers onto the surface of the nickel catalyst. Note that such a mechanism is observed whatever the carbon film is initially localized at the interface of the substrate with the catalyst, or on the top surface of the catalyst. The control of both the homogeneity and the number of graphene layers depends strongly on the solubility and diffusion of carbon and is consequently influenced by heating parameters (heating ramp, temperature and time of heating, cooling ramp) and material parameters (mainly the thicknesses of the carbon film and nickel film). However, the influence of the thickness of the nickel catalyst film on the synthesized graphene has rarely been investigated.

By combining PLD and rapid thermal annealing, transfer-free graphene can be obtained by dewetting the nickel film. By increasing the temperature in a vacuum, dewetting is a spontaneous phenomenon in which a thin film is treated under conditions that allow the system to minimize its interfacial energy by breaking the film up into separate particles or islands.

Dewetting of nickel thin films during graphene synthesis has been observed under different conditions [START_REF] Marchena | Low temperature direct growth of graphene patterns on flexible glass substrates catalysed by a sacrificial ultrathin Ni film[END_REF][START_REF] Nakagawa | A light emitter based on practicable and mass-producible polycrystalline graphene patterned directly on silicon substrates from a solid-state carbon source[END_REF][START_REF] Banno | Transfer-free graphene synthesis on insulating substrates via agglomeration phenomena of catalytic nickel films[END_REF]. Moreover, when an acidic treatment FeCl3 or HCl solution is used, the nickel particles resulting from the dewetting process can be eliminated. This process avoids the need for relatively complicated transfer protocols in which cracks, wrinkles, and contamination of the resulting graphene can occur [START_REF] Srivastava | Novel Liquid Precursor-Based Facile Synthesis of Large-Area Continuous, Single, and Few-Layer Graphene Films[END_REF][START_REF] Xu | Scanning Tunneling Microscopy Characterization of the Electrical Properties of Wrinkles in Exfoliated Graphene Monolayers[END_REF].

In the present work, in the first step, we conducted a detailed parametric study of the influence of the thickness of the nickel and of the annealing temperature on the dewetting of nickel thin film. The morphological analysis was carried out with SEM to observe the effect of these two parameters. In the second step, we investigated the impact of the starting thickness of the nickel catalyst on the synthesized graphene by rapid thermal annealing of the a-C/Ni stacking. The samples were analyzed using SEM-EDS, Raman, UV-Vis, and HRTEM. This study advances our understanding of the influence of the starting thickness of the nickel catalyst on its dewetting process and on the resulting synthesized graphene. Indeed, the effect of the metal catalyst thickness and annealing temperature on the nanoarchitecture of the graphene film are rarely systematically investigated in the literature. From a parametric study based on various nickel film thicknesses (25-150 nm) annealed in the temperature range 500-900°C, we demonstrate the optimized experimental conditions to obtain a dominant graphene bilayer by annealing at 900°C an amorphous carbon films 2 nm thick deposited onto a Ni film catalyst 50 nm thick. In such conditions, the results show that an easy acidic treatment is able to remove the residual nickel catalyst compatible with the existence of the graphene film onto the silica substrate.

Experimental details

Figure 1 shows the different steps used to prepare the sample. SiO2 substrates were ultrasonically cleaned, first in acetone, and then in ethanol, and finally in deionized water baths.

Nickel film (25, 50, 150 nm thick) was deposited by thermal evaporation on top of the cleaned SiO2 substrates in a vacuum chamber pumped to a base pressure of 10 -6 mbar. High purity Ni (99.99%) was molten thermally in a tungsten nacelle and evaporated towards the substrate. Thermal annealing of nickel thin film (labeled A in Fig. 1): After deposition of the nickel thin film (25, 50, 150 nm thick) by thermal evaporation, the Ni/SiO2 samples were annealed using rapid thermal annealing (RTA) to study nickel dewetting. Annealing was performed in a RTA oven at 500, 700, 800, and 900 °C for 420 s in a vacuum pressure of 10 -2 mbar, with a heating rate of +15 °C/s and a cooling rate of about -0.5 °C/s. An annealing time of 420 s was chosen for all temperatures based on our previous investigation of the graphene growth mechanism studied using in situ XPS [START_REF] Bleu | Dynamics of carbon diffusion and segregation through nickel catalyst, investigated by in-situ XPS, during the growth of nitrogen-doped graphene[END_REF], which showed that phase equilibrium was reached at 500 °C with 150 nm of Ni when heated for similar periods of time. In the present study, we thus assumed that phase equilibrium is also reached after heating for 420 s at temperatures ranging from 500-900 °C, with Ni film thicknesses ranging from the 25-150 nm.

Free transfer graphene synthesis process (labeled B in Fig. 1): Ni/SiO2 substrates were introduced in a vacuum PLD chamber pumped to a base pressure of 10 -7 mbar for 2 nm of amorphous carbon (a-C) deposition. Carbon was ablated from a high purity graphite (99.9995%) target using an excimer KrF laser (248 nm wavelength, 20 ns pulse duration, 10 Hz repetition rate) at room temperature. The fluence of the laser beam was kept constant at 5 J.cm -2 . The distance between the sample holder and the graphite target was 40 mm. The final step consisted of annealing the a-C/Ni/SiO2 samples at 900 °C for the transformation of amorphous carbon into graphene. The choice of a-C film thickness (2 nm) and annealing conditions (temperature of 900°C, heating and cooling ramps) is based on our previous graphene synthesis optimization from a wide set of synthesis conditions [START_REF] Bleu | Graphene synthesis on SiO2 using pulsed laser deposition with bilayer predominance[END_REF]. The sample was heated for 420 s at a vacuum pressure of 10 -2 mbar in an RTA oven, with a heating rate of +15 °C/s and a cooling rate of about -0.5°C/s. After graphene growth, the samples were immersed in 4M FeCl3 for 24 h to remove nickel particles. This thermally induced process leads to the gradual formation of nickel particles on the SiO2 substrate, due to minimization of the total surface energy of the system. the second line corresponds to the 50 nm thick film and the third line to the 150 nm thick nickel thin film. The first column in Fig. 2 shows that the nickel thin films as deposited on SiO2 samples are quite homogeneous with low roughness, regardless of their thickness. The second column corresponds to the SEM images of the annealed samples at 500 °C for the three different nickel film thicknesses. From 500 °C upward, the transition between the three above-mentioned stages can be observed, but at different temperatures depending on the starting thickness of the Ni film, as depicted in Fig. 2 and described below. On the one hand, when the Ni film was thin (25 nm), stage 3 occurred when the temperature was as low as 700 °C (Fig. 2c), and higher temperatures only led to a slight increase in the size of the individual Ni particles. On the other hand, when the Ni film was thicker (150 nm), stage 2 was observed at higher temperatures compared to thinner Ni films, as shown in Fig. 2o related to an annealing temperature of 900°C, with an almost continuous surface network of stringy Ni islands that were significantly bigger than with the 50 nm thick Ni at 800 °C (Fig. 2i). No stage 3 was observed in the 150 nm thick Ni. Higher temperatures are probably required to form individual Ni particles. We clearly observed that the three-stage dewetting process depended on the starting thickness of the nickel film and on the annealing temperature. We also observed that dewetting accelerated with increasing thinness of the film, and that the temperature at which dewetting occurred decreased with increasing film thinness, in agreement with

Results

3.1.Effect of rapid thermal annealing on the morphology of nickel thin film

Thompson [START_REF] Thompson | Solid-State Dewetting of Thin Films[END_REF]. In this fundamental article related to solid-state dewetting of thin film, Thompson detailed the mechanism responsible for the dewetting of metastable as-deposited thin films at temperatures well below the film's melting temperature, by the minimization of the total energy of the free surfaces of the film and substrate, and of the film-substrate interface.

A decrease of the film thickness generally induces a decrease of the temperature at which dewetting occurs, due to an increase of the driving force for dewetting and thus an acceleration of the dewetting rate. Preexisting holes, film edges or formation of new holes are mandatory for the dewetting process. As observed in our stage 1, the temperature of hole formation and growth decreases as the Ni film thickness is lower. Then the holes grow to form dewetted areas and often overlap (in agreement with our stage 2), to form a complete dewetted film (in agreement with our stage 3). Thompson noticed that the dewetting temperature decreases with the initial film thickness, and the dewetting-induced islands size and spacing also decrease by the same way. This is also confirmed by Geissler et al. [START_REF] Geissler | Effect of Hydrogen Pressure on the Size of Nickel Nanoparticles Formed during Dewetting and Reduction of Thin Nickel Films[END_REF] in an experimental configuration close to ours. This could explain why the 25 nm thick Ni film started to coalesce at a lower temperature than the thicker Ni films, and why the thickest film (150 nm) started to coalesce into nickel islands at the highest temperatures. In other words, the transition between the three above-mentioned stages occurred at higher temperatures with increasing thickness of the Ni film.

Using ImageJ software, the SEM images in Fig. 2 were used to extract information concerning surface coverage by the Ni islands or particles, the perimeter of the particles, and interparticle spacing (i.e. the distance to the nearest neighbor particles), as seen in Table 2. Whatever the thickness of the film, the surface coverage by the stringy Ni islands (stage 2) or particles (stage 3) decreased, from 21% to 16% in the 25 nm thick film, from 24% to 16% in the 50 nm thick film, and from 58% to 35% in the 150 nm thick film, all with an increase in temperature. This is consistent with the dewetting and coalescence mechanism described above.

Moreover, at the highest temperature of 900 °C, the thicker the original Ni film (150 nm), the higher the surface coverage. The particle perimeter and interparticle distance could only be extracted and compared in stage 3, i.e. with the 25 nm thick film annealed at 700, 800, and 900 °C, and with the 50 nm thick film annealed at 900 °C. Fig. 3 shows the size distribution of the perimeter of the Ni particles associated with the dewetting process of 25 nm thick nickel film.

The average particle perimeters were 1.47 ± 0.5, 1.88 ± 0.5 and 1.70 ± 0.8 µm, and the interparticle spacing was 0.62, 0.80, 0.84 µm, at annealing temperatures of 700, 800, 900 °C, respectively. At the highest temperature of 900 °C, the perimeter of the particles related to the thicker 50 nm film was slightly more than double compared to the 25 nm thick film (3.9 µm vs 1.7 µm) at the same temperature, and the interparticle spacing was a little less than double (1.50

µm compared to 0.84 µm), with a similar surface coverage of 16%. Thus, at a given temperature, we observed a significant dependence of particle size and distribution with the initial nickel film thickness. similar thermo-kinetic experimental heating conditions. Finally, we cannot exclude the possibility that residual Ni was still present in the Ni particles, implying that Ni dewetting was not complete, even at 900 °C. This hypothesis is examined in the following section related to the behavior of the Ni film at the highest temperature (900 °C) using a carbon film to achieve graphene synthesis.

Influence of nickel thickness on the transformation of amorphous carbon into graphene after thermal annealing at 900 °C

At the highest RTA temperature of 900°C and 10 -2 mbar pressure used in our study, the nickel was still well below its melting point (1455 °C). It therefore remained in solid-state, but was progressively dewetted, as evidenced in the previous section, via the three-stage mechanism with varying temperature thresholds depending on the starting thickness (25, 50, a. Graphene growth using a 25 nm thick nickel thin film catalyst Fig. 4 shows the results of Raman analysis of the synthesized graphene using the 25 nm thick nickel catalyst film, after thermal annealing at 900 °C. The most significant peaks for graphene films revealed by Raman spectroscopy are D, G, and 2D, located around 1,350, 1,580, and 2,700 cm -1 respectively. In addition, their intensity ratio can be used to estimate the presence of defects (ID/IG) and the number of graphene layers (I2D/IG). To distinguish between monolayer, bilayer and few-layer graphene, we considered that an I2D/IG ratio >1.4 is associated with the formation of monolayer graphene, an I2D/IG ratio located between 0.75 and 1.4 is associated with a bilayer graphene, and an I2D /IG ratio < 0.75 is associated with few-layer graphene (3 or more layers). These considerations are reported in [START_REF] Ferrari | Raman Spectrum of Graphene and Graphene Layers[END_REF][START_REF] Graf | Raman mapping of a single-layer to double-layer graphene transition[END_REF][START_REF] Malard | Raman spectroscopy in graphene[END_REF][START_REF] Gong | Layer-Controlled and Wafer-Scale Synthesis of Uniform and High-Quality Graphene Films on a Polycrystalline Nickel Catalyst[END_REF][START_REF] Xiong | Single-Step Formation of Graphene on Dielectric Surfaces[END_REF][START_REF] Peng | Direct Growth of Bilayer Graphene on SiO2 Substrates by Carbon Diffusion through Nickel[END_REF]. Due to the penetration depth of the Raman probe, it is worth noting that all these maps include the graphene on the surface of the nickel particles as well as the graphene at the interface between the nickel nodules and the SiO2 substrate.

Fig. 4a shows the Raman mapping of the ID/IG ratio, where the average value is 0.25 with a very low standard deviation of 0.05, suggesting the good uniformity of the synthesized graphene with low defect density. Fig. 4b shows the Raman mapping of the I2D/IG ratio with a mean value of 0.62 and a low standard deviation of 0.05. This result demonstrates the formation of a uniform few-layer (3-6 layers) graphene using a 25 nm thick nickel film catalyst. Fig. 4c shows a representative spectrum extracted from Raman mapping. In this spectrum, the D, G, and 2D peaks are located at 1,372, 1,587, 2,746 cm -1 , respectively. The intensity ratios are 0.21 for ID/IG and 0.67 for I2D/IG. The average crystallite size La is 44 nm. This value is derived from the ID/IG ratio by the mean of the Tuinstra-Koenig equation [START_REF] Cançado | General equation for the determination of the crystallite size La of nanographite by Raman spectroscopy[END_REF]. Fig. 4d illustrates the predominance of few-layer (3-6 layers) graphene with the statistical histogram of the Raman mapping of the I2D/IG ratio showing the distribution of the number of graphene layers. Indeed, with the 25 nm thick Ni film, only 5% of the mapped area is a bilayer, whereas three or more graphene layers cover 95% of the area. This suggests that the synthesized graphene is uniform even with the presence of the nickel particles derived from the dewetting of the nickel catalyst film. Fig. 5a shows the SEM image of the as-grown graphene using the 25 nm thick nickel film catalyst after thermal annealing at 900 °C. A similar nickel island distribution as that obtained with the 25 nm thick Ni film annealed at the same temperature (Fig. 2e) is observed. By comparing the statistical values of the pure Ni film (Fig. 3a) with the same film covered by graphene, the perimeter of the nickel particles is reduced from 1.70 µm without graphene to 1.04 µm with graphene. The surface coverage decreased from 16 to 11% and the average distance between the particles decreased slightly from 0.80 to 0.70 µm. This difference may be due to the presence of dissolved carbon in the nickel, which modifies the surface energy of the nickel during the dewetting process, as discussed in the Discussion section. 3, for the as-grown graphene and the FeCl3 treated graphene.

For the as-grown graphene (Fig. 5b), the spectra were captured by focusing the electron-beam spot either on the nickel particle (lower spectrum), or on the graphene layer (upper spectrum).

The results revealed that these two areas contain nickel and other expected elements such as C, O, and Si. However, the area corresponding to the Ni particles contains a bit more nickel than the other region. This means that the dewetting of Ni on the original surface was not complete, even at 900 °C. However, after FeCl3 treatment, the EDS spectra recorded both inside and outside the footprints left by the removed nickel particles (Fig. 5d and Table 3) showed no Ni signals. This result is consistent with previously reported studies [START_REF] Nakagawa | A light emitter based on practicable and mass-producible polycrystalline graphene patterned directly on silicon substrates from a solid-state carbon source[END_REF][START_REF] Banno | Transfer-free graphene synthesis on insulating substrates via agglomeration phenomena of catalytic nickel films[END_REF] on acidic etching to obtain transfer-free graphene.

Table 3: Quantitative EDS analysis, before and after FeCl3 treatment, of the graphene surface synthetized using the 25, 50 and 100 nm thick nickel catalyst films, after thermal annealing at 900 °C.

Fig. 5e shows the Raman mapping of the I2D/IG ratio in a 20 ×20 μm² region associated with interfacial graphene after treatment with FeCl3, with an average value of 0.58. The inset shows a representative spectrum extracted from the Raman mapping. Both exhibit the same characteristics as the spectrum for as-synthesized graphene shown in Fig. 4b-c. The surface graphene distribution is uniform, like the as-grown graphene. However, we observed a decrease of the I D /I G ratio, from 0.25 ± 0.05 before the acidic treatment to 0.19 ± 0.12 after the acidic treatment, consistent with a decrease of the defective level and/or increase of size of the graphitic clusters in the graphene layers. This suggests that the FeCl3 treatment is a transferfree process that allows the removal of the Ni catalyst with no significant alteration of the dominant few-layer architecture, but with some modifications on the defective level of the graphene films. From our best of knowledge, this last observation has never been reported nor discussed previously in the literature. Its interpretation requires more specific attention in the future. Fig. 5f shows the HRTEM images of the graphene after FeCl3 treatment. The images, typical of graphene edges, is an accurate way to measure the number of graphene layers at different locations. Here, the synthetized graphene from 25 nm thick Ni displays five lines representing the five layers graphene (Fig. 5f) revealed by Raman analysis.

b. Graphene growth using 50 nm thick nickel thin film catalyst

Like for the synthesized graphene using 25 nm thick nickel film, Raman analysis and SEM-EDS were performed for the as-grown graphene on the 50 nm thick nickel after thermal annealing at 900 °C. Again, all the maps include the graphene on the surface of the nickel particles as well as the graphene at the interface between the nickel nodules and the SiO2 substrate.

Fig. 6a shows the Raman mapping of the ID/IG ratio, where the average value is 0.26 with a low standard deviation of 0.13, suggesting the density of defects in the synthesized graphene is reasonably uniform. Fig. 6b shows the Raman mapping of the I2D/IG ratio with a mean value of 1.08 and a high standard deviation of 0.38. This result demonstrates the formation of continuous, but non-uniform graphene using 50 nm thick nickel catalyst. The graphene derived from the 50 nm thick nickel is indeed heterogeneous, containing monolayer, bilayer, and fewlayer graphene. This observation was confirmed by the statistical histogram of the Raman mapping of the I2D/IG ratio showing the distribution of the number of graphene layers in Fig. 6c. From these statistical data, 7% of the mapped area were few-layer (3 and more layers), 70%

were bilayer and 23% were monolayer, suggesting the bilayer predominance in the mapped area. Fig. 6d shows the different types of Raman spectra representative of monolayer, bilayer, and few-layer graphene with their characteristic values. This is the same finding as that reported in our previous study [31] confirming our method is reproducible. Representative spectra from the mapping of the as-grown graphene, their positions are highlighted with the corresponding number of the layer in the Raman mappings.

Fig. 7a shows the SEM image of the as-grown graphene using 50 nm thick nickel catalyst. Like the annealed 50 nm thick nickel, this sample displays many island-shaped nickel particles.

Comparison of the statistical values showed that the perimeter of nickel particle decreased from 3.9 µm with no graphene to 2.34 µm with graphene. The surface coverage decreased slightly from 16 to 15% and the average distance between the particles from 1.50 to 1.10 µm. This is the same trend as that observed using 25 nm thick nickel film. The SEM image (Fig. 7c) of the graphene treated with FeCl3 shows that the round-shaped nickel particles are no longer present.

Elemental analysis with EDS was performed of the as-grown graphene and of the treated graphene. The results showed the presence of nickel in the as-synthesized graphene sample (Fig. 7b and Table 3), while the removal of nickel was confirmed in the treated graphene spectrum (Fig. 7d and Table 3). Fig. 7e shows the Raman mapping of the I2D/IG ratio in a 20 ×20 μm² region with an average value of 0.91, associated with the graphene treated with FeCl3 leading to the interfacial graphene. The inset spectrum shows the one of bilayer graphene. As for the 25 nm thick film, we also observed a decrease of the I D /I G ratio, from 0.26 ± 0.13 before the acidic treatment to 0.15 ± 0.10 after the acidic treatment, consistent with an effect of the acidic treatment on the defective level and/or size of the graphitic clusters in the graphene layers, which remains not explained at the present stage of investigation. This mapping shows that the interfacial graphene has the same characteristics as the as-grown graphene, except the defective level, meaning the interfacial graphene is also continuous but non-uniform, as it contains monolayer, (mainly) bilayer, and some few-layer graphene. Fig. 7f shows the HRTEM images of the edges in the bilayer graphene region displaying a double line. The interplanar spacing estimated from the intensity profile images was 0.345 nm, as shown in the insets of Figs. 5f and7f. Such a value is in agreement with previously reported works [START_REF] Kalita | Monolayer graphene from a green solid precursor[END_REF][START_REF] Sharma | Influence of gas composition on the formation of graphene domain synthesized from camphor[END_REF]. Fig. 7g shows a typical graphene monolayer region indicated by the red circle, and Fig. 7h shows the hexagonal structure of this typical monolayer illustrated with the purple dots. The HRTEM examination again confirms that the starting thickness of the nickel strongly affects the final synthesized graphene layers, thereby confirming our Raman results.

c. Graphene growth using 150 nm thick nickel thin film catalyst

Graphene was formed using a 150 nm thick nickel film as catalyst after thermal annealing at 900 °C. Like the annealing response with 150 nm, where thick nickel differed from the response when 25 and 50 nm thick nickel was used, the resulting graphene also differed. The first striking point is that the synthesized graphene was not continuous as can be seen in Fig. 8. Fig. 8a shows the SEM image of the as-grown graphene using 150 nm thick nickel. This image has the same features as with the 150 nm thick nickel film annealed at 900 °C, with the agglomeration of stringy nickel islands, which are less connected than in the case with no carbon. In addition, graphene formed on the surface of nickel islands and in the interface between the nickel and the SiO2 substrate, like with 25 and 50 nm thick nickel. The difference here is the presence of graphene with a different contrast: dark contrast with more layers and bright contrast with a few layers, as reported in previous works [49 -51]. The locations of the thin and thick graphene layers are identified by the layer numbers in the SEM image. Fig. 8b and Table 3 presents the EDS analysis. Clearly the synthesized graphene is not continuous. Fig. 8c shows the representative Raman spectra of the synthesized graphene using 150 nm thick nickel. The resulting graphene is not continuous; it contains monolayer, bilayer, and few-layer graphene like that derived from 50 nm thick nickel film. It is heterogeneous, with a very low defect density and larger crystallites than the graphene derived from 25 and 50 nm thick nickel film. The Raman spectrum of the area without graphene is presented at the bottom of Fig. 8c, showing no signal. This result is consistent with the synthesis graphene using nickel catalyst film with a starting thickness < 170 nm [START_REF] Peng | Direct Growth of Bilayer Graphene on SiO2 Substrates by Carbon Diffusion through Nickel[END_REF]. Raman mapping was performed to provide more arguments for the discontinuity and the non-uniformity of the synthesized graphene. Fig. 8 d-e show Raman mapping of the G and 2D peak intensities, respectively, where the low-intensity areas are regions with no graphene. From all these analyses, we concluded that 150 nm thick nickel catalyst will not produce continuous graphene when 2 nm of amorphous carbon is used as a carbon source and 900 °C is used as processing temperature.

Discussion

4.1.Nickel thin film dewetting during rapid thermal annealing

In the results section, we demonstrated that the dewetting of nickel thin film during rapid thermal annealing leads to the formation of nickel particles. These results are crucial for the interpretation of results obtained in the presence of carbon for graphene synthesis and are discussed in the following sub-section.

The shape, size, surface coverage, and interspacing of these particles depend on the starting thickness of the film and on the annealing temperature. Table 2 summarizes the statistical values extracted from the SEM images in Fig. 2, 5a, 7a, and 8a.

We observed a huge effect of temperature on the shape, size, surface coverage, and interspacing of the Ni particles. Indeed, whatever the starting thickness of the nickel, the statistical parameters concerned evolved when the annealing temperature was changed. This effect shows that the formation process of the nickel particles is thermally activated, in agreement with Ostwald's ripening and atomic diffusion, these being the mechanisms generally put forward to explain the growth of particles from a thin metal film [START_REF] Chhowalla | Growth process conditions of vertically aligned carbon nanotubes using plasma enhanced chemical vapor deposition[END_REF][START_REF] Carey | Formation of low-temperature self-organized nanoscale nickel metal islands[END_REF][START_REF] Mougin | Thermal stability and reconstruction of nanoparticulate Au film on model molecular surfaces[END_REF]. In fact, in Ostwald's ripening, the mass transport of individual metal atoms or clusters occurs at temperatures below the melting point of the metal. Moreover, the temperature at which dewetting occurs is lower for thinner films, and the island size scales with the film thickness [START_REF] Nuryadi | Thermal agglomeration of single-crystalline Si layer on buried SiO2 in ultrahigh vacuum[END_REF]. We believe that our nickel dewetting process is due to Ostwald's ripening, as reported in previous studies on the nickel dewetting process [START_REF] Geissler | Effect of Hydrogen Pressure on the Size of Nickel Nanoparticles Formed during Dewetting and Reduction of Thin Nickel Films[END_REF][START_REF] Carey | Formation of low-temperature self-organized nanoscale nickel metal islands[END_REF]. It has been also reported [START_REF] Sudheer | A study of growth and thermal dewetting behavior of ultra-thin gold films using transmission electron microscopy[END_REF] that the surface coverage decreases with an increase in the annealing temperature. Such a behavior is also observed in our study:

whatever the starting thickness of the nickel film, the surface coverage decreased with an increase in temperature.

In the presence of carbon, the size, spacing, and surface coverage of the Ni islands decreased in comparison to in the absence of carbon. This suggests that carbon favors the dewetting of nickel particles, in agreement with the work of Diarra et al. [START_REF] Diarra | Importance of Carbon Solubility and Wetting Properties of Nickel Nanoparticles for Single Wall Nanotube Growth[END_REF]. Furthermore, the dewetting of nickel is much more pronounced with a decrease in the thickness of the original nickel film.

From all these results, we conclude that the most important aspects that affect the nickel islands derived from the dewetting of nickel thin film are the annealing temperature, the starting thickness of the nickel film, and the presence of carbon deposited prior to rapid thermal annealing.

4.2.Influence of the initial thickness of nickel thin film catalyst on graphene synthesis

In the results section, we demonstrated that the synthesized graphene resulting from the transformation of amorphous carbon using nickel catalyst is highly impacted by the starting thickness of the nickel catalyst film. However, a further increase in nickel thickness up to 150 nm markedly affected the resulting graphene, which was non-continuous, even though monolayer, bilayer, and few-layer graphene with very low defect densities were observed. On one hand, this surface discontinuity may be due to the large attached nickel islands derived from the dewetting process of the 150 nm thick nickel film, or, on the other hand, to the low concentration of dissolved carbon that diffused deep into the thick nickel film. Because of the marked surface heterogeneity, it was not possible to perform the Raman statistical analysis to get an overview of the graphene layer distribution.

From these results, we conclude that the larger amount of graphene is precipitated from the thinner nickel films whereas a smaller amount of graphene is precipitated from the thicker nickel films. Furthermore, as for the quality of graphene films, we can speculate that the increase in the number of layers is caused by the structural disorder of graphene films. This shows that the number of layers and the quality of the film (in terms of defects) can be controlled by choosing the appropriate thickness of the nickel for a given temperature.

In addition, let us recall that using 25, 50, and 150 nm thick Ni, the graphene not only forms on the surface of the nickel but also at the interface between the nickel and the SiO2 substrate. This occurs because carbon diffuses through the nickel film during thermal annealing and segregates out of both sides of the Ni film, as illustrated in Figure 9b, which summarizes the mechanisms deduced from our experiments. In our recent study [START_REF] Bleu | Dynamics of carbon diffusion and segregation through nickel catalyst, investigated by in-situ XPS, during the growth of nitrogen-doped graphene[END_REF], using in situ XPS analysis, we demonstrated that graphene already forms at 500 °C through carbon diffusion and segregation in the nickel catalyst during the annealing process. A similar mechanism also occurs with thermal annealing up to 900 °C, but the highest temperatures also induce nickel dewetting, as we observed here. More precisely, as described in Fig. 9, three main phenomena occur when the temperature is increased to 900 °C:

• At the lowest temperatures, typically 500 °C, carbon diffusion inside the Ni film (forming a Ni(C) film) and carbon segregation on both sides of the nickel film occur, forming defective graphene both on the surface of the Ni(C) film and at the interface between the Ni(C) film and the substrate, as shown in Fig. 9b. This explanation is based on the results of our previous work [START_REF] Bleu | Dynamics of carbon diffusion and segregation through nickel catalyst, investigated by in-situ XPS, during the growth of nitrogen-doped graphene[END_REF], which showed graphene formation after annealing at 500 °C without Ni dewetting at this temperature.

• At higher temperatures (the exact values depend on the thickness of the Ni film), the dewetting of the Ni(C) film starts with the appearance of holes that grow in size, progressively leading to the formation of nickel islands, as depicted in Fig. 9c. This phenomenon does not prevent the graphene growth process producing less defective graphene present both around the nickel islands and on the surface of the substrate, despite retraction of the nickel film.

• At the highest temperatures, the final stage of the nickel dewetting transforms the nickel islands into individual particles (Fig. 9d) that are easily removed from the surface by chemical etching if the initial Ni film was sufficiently thin (25-50 nm). At this final stage, the surface of the SiO2 substrate remains covered by large extents of graphene (Fig. 9e).

Deduced from our observations, this mechanism shows that the graphene synthesis is compatible with the nickel dewetting during thermal annealing. However, it depends to a great extent on the initial thickness of the nickel film and on the annealing temperature. Indeed, using 25 and 50 nm thick nickel film, we observed the continuous surface and interfacial graphene growth with the formation of spherical nickel particles. When using 150 nm thick nickel, we observed non-continuous surface and growth of interfacial graphene with stringy nickel particles. In previous papers, Prekodravac et al. [59,[START_REF] Prekodravac | The effect of annealing temperature and time on synthesis of graphene thin films by rapid thermal annealing[END_REF] also observed the formation of graphene films with attention to the catalyst dewetting during annealing. In one study

[59], a 200 nm thick carbon-doped nickel film was transformed into monolayer graphene islands among nickel grains, by RTA within 900-1000°C. In another study [START_REF] Prekodravac | The effect of annealing temperature and time on synthesis of graphene thin films by rapid thermal annealing[END_REF], the authors used a bilayer Ni(50nm)/Cu(700 nm) deposited on polished polycrystalline graphite, annealed within 600-900°C for 30 mn, and at 900°C during longer periods. The lowest annealing temperatures led to discontinuous, high defective monolayer of graphene, whereas the highest temperatures led to homogeneous multilayer graphene with a lower defective content. In spite of a different configuration of metal catalyst, our investigations at 900°C confirm those previous works and widens the possibility to control the graphene growth concomitant with the catalyst dewetting in a similar way. Finally, after removal of the nickel islands with FeCl3 treatment, we performed UV-Vis analysis on the continuous interfacial graphene obtained with the 25 and 50 nm thick nickel film, to quantify transmittance. Fig. 10 shows measurement of transmittance of graphene derived from both 25 and 50 nm nickel after etching of nickel particles. The transmittance of the derived graphene from 25 nm nickel at 550 nm was ~84 %, which is consistent with values reported [61-63] for few-layer graphene (~3-6 layers). The transmittance value of the graphene resulting from 50 nm nickel was much higher, ~88%, which is consistent with the previously reported values [31,64,65] for bilayer graphene. Indeed, the transmittance of the synthetized graphene from 25 nm nickel was lower than the transmittance of graphene resulting from 50 nm thick nickel because it has more layers, as indicated by Raman data. These results are consistent with the principle that the optical transmittance is strongly correlated with the number of graphene layers. Graphene transmittance thus decreases with an increase in the number of layers [66-68].

Conclusions

Here, we investigated the transformation of a thin amorphous carbon (a-C) film into transferfree graphene using nickel catalyst dewetting phenomena. We conducted a systematic study of nickel dewetting, as well as of the effect of nickel thickness on graphene growth. The a-C layer was deposited on a Ni/SiO2 substrate, followed by rapid thermal annealing. The annealing step caused the catalyst layer to fragment into stringy islands and particles, and graphene films formed on the surface of the nickel particles and at the interface between the nickel particles and the SiO2 substrate. The most crucial parameters responsible for changes in the Ni film are annealing temperature, the thickness of the initial nickel film, and the thin carbon layer deposited on Ni prior to rapid thermal annealing that partially dissolved into Ni at high temperatures. Microscopic Raman mapping, SEM and HRTEM indicated that graphene films were preferentially continuous when 25 and 50 nm thick nickel was used, whereas the graphene synthetized from 150 nm thick nickel was discontinuous. We also confirmed that both the thickness of the graphene layer and the size of the nickel particles depend on the starting thickness of the nickel. The synthesized graphene films had better structural qualities and fewer layers when the thickness of the nickel catalyst was increased from 25 to 50 nm. With acidic etching of the residual nickel, the substrate with graphene regained high transparency of about 88% corresponding to the bilayer interfacial graphene for the derived graphene from 50 nm of nickel. Our method thus extends the range of substrate materials on which graphene can be directly synthesized, thereby avoiding relatively complicated, costly and not always defect-free transfer techniques. We believe the present results provide useful information for a future graphene synthesis process using a catalytic reaction.

Figure 1 :

 1 Figure 1: Synthesis route for (A) rapid thermal annealing of Ni thin films and (B) free-transfer graphene films obtained by pulsed laser deposition of carbon on Ni thin films followed by rapid thermal annealing and Ni etching. In both cases, the substrate was SiO2. Inspired from [31], with permission.

Fig. 2a ,

 2a Fig. 2a, f, and k show that the nickel thin film completely and uniformly covered the SiO2 substrate before the thermal annealing process started. With annealing at increasing temperatures, a reduction in the extent of the surface covered by nickel was observed. This was due to a dewetting process of the nickel film on the SiO2 surface, as already observed with various metallic thin films annealed in vacuum conditions [32-36]. The dewetting process of continuous metal films generally takes place in three successive stages: 1) holes form inside the Ni film due to the beginning of surface Ni diffusion (stage 1), 2) the density of holes increases with the transition from the continuous Ni film to an almost continuous surface network of stringy Ni (stage 2), 3) the final transition occurs from the stringy Ni network to a surface distribution of individual Ni (sub-) micrometer-sized particles (stage 3).

Fig. 2

 2 Fig.2shows SEM images of the surface of the annealed nickel thin film of varying thickness (25, 50 and 150 nm) on top of the fused silica SiO2 substrates after annealing at 500 °C ((b) (g) and (l)), 700 °C ((c), (h) and (m)), 800 °C ((d), (i) and (n)), 900 °C ((e), (j) and (o)). The first line corresponds to the images of changes in the 25 nm thick nickel thin film during dewetting;

Figure 2 :

 2 Figure 2: Summary of the solid-state dewetting behavior of nickel thin films deposited on a fused silica SiO2 substrate: SEM images of the dewetting of 25 nm thick nickel thin film (a-e), 50 nm thick (f-j) and 150 nm thick (k-o), as a function of annealing temperature (range 500-900 °C). The three stages related to the Ni dewetting mechanism, described in the text, are superimposed on the SEM images.

Stage 1 ,

 1 corresponding to the formation of spherical holes was observed at 500 °C, with different hole sizes and densities depending on the thickness of the Ni film. Stages 2 and 3 were clearly observed in 50 nm thick Ni within the 700-900 °C range. At 800 °C (Fig. 2i), the end of stage 2 was visible with an almost-continuous surface network of stringy Ni being transformed into individual Ni particles corresponding to the beginning of stage 3. At 800 °C, the stringy Ni particles were less separated than at 900 °C (Fig. 2j) clearly corresponding to stage 3 with a surface distribution of individual Ni (sub-) micrometer-sized particles.

Figure 3 :

 3 Figure 3: Particle size distribution corresponding to the 3 rd stage of the Ni dewetting process, obtained using ImageJ software on the SEM images in Fig.2, and related to the 25 nm thick Ni film after thermal annealing at 700 °C (a), 800 °C (b) and 900 °C (c), and the 50 nm thick Ni film after thermal annealing at 900 °C (d).

Figure 4 :

 4 Figure 4: Raman analysis of the synthesized graphene using a 25 nm thick nickel catalyst: (a) Raman mapping of the ID/IG ratio in a 20 ×20 μm² region with the average value of 0.25; (b) Raman mapping of the I2D/IG ratio in a 20 ×20 μm² region with the average value of 0.62; (c) A representative spectrum extracted from the mapping of the synthesized graphene: its position is shown by the white diamonds on the Raman maps; (d) Statistical histogram of the Raman mapping of I2D/IG ratio showing the predominance of few-layer graphene.

Figure 5 :

 5 Figure 5: (a) SEM image of the as-synthesized graphene using 25 nm thick nickel catalyst, after annealing at 900 °C; (b) EDS spectra of two different regions of the samples, the grey-black zone (at the top) and the white zone (below); (c) SEM image of the graphene treated with FeCl3 to remove the nickel particles leading to the appearance of the interfacial graphene; (d) EDS spectra of two different regions of the samples, the zone with traces of islands (at the top) and the grey-black zone (below), both showing the absence of nickel; (e) Raman mapping of the I2D/IG ratio in a 20 ×20 μm² region with an average value of 0.58 of the interfacial graphene after FeCl3 treatment. The inset shows a representative spectrum extracted from Raman mapping; (f) HRTEM image of the graphene edges after FeCl3 treatment showing five layers. The inset is the intensity profile image.

Fig. 5c shows

  Fig. 5c shows SEM image of the graphene treated with FeCl3 acidic solution; this graphene can be called interfacial graphene because the other graphene on the surface of the nickel nodules probably disappeared with the removal of residual nickel. Spherical white traces left by the disappearance of the nickel nodules are visible. Fig.5 b, d show EDS spectra, with atomic concentrations depicted in Table3, for the as-grown graphene and the FeCl3 treated graphene.

Before FeCl 3 FeCl 3 C

 33 After (at.%) O (at.%) Ni (at.%) Si (at.%) C (at.%) O (at.%) Ni (at.%) Si (at.%)

Figure 6 :

 6 Figure 6: Raman analysis of the as-synthesized graphene using 50 nm thick nickel catalyst film: (a) Raman mapping of the ID/IG ratio in a 20 ×20 μm² region with the average value of 0.26; (b) Raman

Figure 7 :

 7 Figure 7: (a) SEM image of the as-synthesized graphene using the 50 nm thick nickel catalyst film. (b) EDS spectra of two different regions of the samples, the zone with the white islands (at the top) and the grey-black zone (below). (c) SEM image of the graphene treated with FeCl3 to remove the nickel particles leading to the appearance of interfacial graphene (d) EDS spectra of two different regions of the samples, the zone with traces of islands (at the top) and the grey-black zone (below), both showing the absence of nickel. (e) Raman mapping of I2D/IG ratio in a 20 ×20 μm² region with the average value of 0.91 of the graphene treated with FeCl3. The inset shows a bilayer graphene spectrum from the Raman mapping of the Fecl3 treated graphene. (f) HRTEM of graphene edges resulting from the use of 50 nm thick nickel, showing two layers after FeCl3 treatment. The inset is the intensity profile image. (g -h)HRTEM of resulting graphene from the use of 50 nm thick nickel, showing a "one monolayer" area (red circle) and the hexagonal atomic resolution of the monolayer graphene. The purple dots in the inset in Fig.7hhighlight the hexagonal structure of graphene.

Figure 8 :

 8 Figure 8: (a) SEM image of the as-synthesized graphene using the 150 nm thick nickel catalyst film, showing a dark and bright contrast for thicker and thinner graphene, respectively. (b) EDS spectra of two different regions of the samples, the grey-black zone (on the left) and the white islands zone (on the right). (c) Representative spectra from the sample of the as-grown graphene, their positions are identified by the number of the corresponding layer in the Raman mapping. (d) Raman mapping results of G peak intensity with a sample area of 20 ×20 μm². (e) Raman mapping results of 2D peak intensity with a sample area of 20 ×20 μm².

Figure 9 :

 9 Figure 9: Schematic illustration of graphene growth on the surface of nickel film and in the interface between the Ni and SiO2 substrate during the nickel dewetting process. (a) The initial stage of the a-C/Ni/SiO2 before the rapid thermal annealing process. (b) The stage of carbon diffusion and segregation through the nickel leading to the initial formation of graphene before nickel dewetting begins. (c) The stage related to the beginning of the nickel dewetting. (d) The stage with the end of the nickel dewetting process. During stages (c) and (d), the initially formed graphene certainly undergoes further changes in nanostructure. (e) Interfacial graphene obtained with the thinnest Ni thicknesses (25-50 nm) after the removal of nickel particles with FeCl3 treatment.

Figure 10 :

 10 Figure 10: Transmittance curves as a function of wavelength for graphene derived from 25 nm thick nickel (bottom) and synthesized graphene derived from 50 nm thick nickel (middle) after thermal annealing and FeCl3 etching and the blank fused silica (top). The inset at the bottom of the figure shows the appearance of both samples after graphene growth and Ni etching.

Table 1

 1

	summarizes the processing conditions

Table 1 :

 1 Summary of growth conditions.

  Graphene was characterized by Raman spectroscopy using an Aramis Jobin Yvon spectrometer (Horiba Jobin Yvon, Gières, France), with 442 nm (2.81 eV) excitation laser-focused through an ×100 objective with a high aperture, guaranteeing the micrometric resolution of the analysis, and providing precise Raman mapping of the samples. To analyze the uniformity of the synthesized graphene, mapping of the samples over probed surfaces 20 × 20 micrometers in size, was performed with graphene at 442 nm, totaling 400 Raman spectra per map with a 1 µm

	spot size collected for each sample. Scanning electron microscopy (SEM) coupled with EDS
	was performed using a FEI Novanano SEM 200 operated at 15kV. The statistical values were
	extracted from the SEM images using ImageJ software. UV-Visible spectroscopy in
	transmission mode was performed by a spectrophotometer Cary50 Probe (Varian) within the
	spectral range 200-800 nm. High-resolution transmission microscopy (HRTEM) was
	performed using a JEOL NEOARM microscope, equipped with a spherical aberration corrector,
	operating at an acceleration voltage of 60 kV and an emission current of 10 μA. Free transfer
	graphene sheets were collected on a holey carbon copper grid. The spatial resolution was < 0.1
	nm.

Table 2 :

 2 Summary

of the statistical values of the average perimeter, surface coverage, and interspacing of nickel particles extracted from the SEM images in Fig.

2

, 5a, 7a et 8a.

  150 nm) of the Ni film. However, data in the literature on graphene synthesis using a solid carbon film in the presence of a Ni catalyst, indicate that carbon dissolves into Ni in a temperature range corresponding to the dewetting process of the Ni film, before its surface segregation into graphene layers[START_REF] Bleu | Dynamics of carbon diffusion and segregation through nickel catalyst, investigated by in-situ XPS, during the growth of nitrogen-doped graphene[END_REF][START_REF] Elnobi | Room-temperature graphitization in a solid-phase reaction[END_REF]. The objective of this section is thus to elucidate how nickel dewetting remains compatible with the synthesis of graphene and to assess the quality of graphene obtained in such conditions. Ideally, such a process would avoid having to transfer the graphene onto another substrate, if the residual Ni particles could be removed from the surface, for example with an acidic treatment. This section is thus focused on the formation of graphene from a very thin carbon film (2 nm), deposited on the 25, 50, and 150 nm thick Ni film, after RTA at 900 °C. We selected the highest temperature studied in the previous section to investigate graphene formation coupled with the most advanced stage of Ni dewetting, considering the annealing temperature range available in our set of experiments.

Table 4

 4 summarizes the different characteristics of the graphene resulting from the synthesis process using 25, 50, and 150 nm thick nickel film. The results reported in Table4show that increasing the nickel thickness from 25 to 50 nm reduces the number of layers in the resulting graphene. This is consistent with previously reported works [28,57,58], in which the graphene films derived from thicker metal films have better structural qualities with fewer layers. Indeed, by increasing the nickel thickness from 25 to 50 nm, the graphene layer number switched from few-layer (3-6 layers) to bilayer predominance. In both cases, the derived graphene was continuous with low defect density. In fact, on metals with significant carbon solubility such as nickel, the formation of heterogeneous graphene with

	monolayer, bilayer, and few-layer is very common because of the additional graphene growth
	from the carbon reservoir in the catalyst bulk. Nevertheless, this segregation effect seems to be
	limited when 50 nm thick nickel is used compared with 25 nm thick nickel thin film, probably
	because a thicker Ni film (50 nm) presents a "deeper" reservoir of carbon than a thinner Ni film
	(25 nm) even when similar heating treatment is used for the two films. This may explain why
	the synthesized graphene was thicker with the 25 nm nickel film and thinner with the 50 nm
	nickel film.
	Nickel thickness (nm)	Processing conditions	a-C thickness (nm)	Derived Graphene
	25			Continuous uniform few-layer graphene
		900 °C with a heating rate of		Continuous heterogeneous
	50	15 °C/s, for 420 s and a	2	graphene with predominance
		cooling rate of 0.5 °C/s		of bilayer
	150			Non-continuous heterogeneous graphene

Table 4 :

 4 Summary of the different characteristics of the graphene resulting from the synthesis process using 25, 50, and 150 nm thick nickel film.

Acknowledgements

This work was supported by the LABEX MANUTECH-SISE (ANR-10-LABX-0075) of Université de Lyon, as part of the program "Investissements d'Avenir" (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR).