Plasma Processing and Treatment of 2D Transition Metal Dichalcogenides: Tuning Properties and Defect Engineering.

Two-dimensional transition metal dichalcogenides (TMDs) offer fascinating opportunities for fundamental nanoscale science and various technological applications. They are a promising platform for next generation optoelectronics and energy harvesting devices due to their exceptional characteristics at the nanoscale, such as tunable bandgap and strong light-matter interactions. The performance of TMD-based devices is mainly governed by the structure, composition, size, defects, and the state of their interfaces. Many properties of TMDs are influenced by the method of synthesis so numerous studies have focused on processing high-quality TMDs with controlled physicochemical properties. Plasma-based methods are cost-effective, well controllable, and scalable techniques that have recently attracted researchers' interest in the synthesis and modification of 2D TMDs. TMDs' reactivity toward plasma offers numerous opportunities to modify the surface of TMDs, including functionalization, defect engineering, doping, oxidation, phase engineering, etching, healing, morphological changes, and altering the surface energy. Here we comprehensively review all roles of plasma in the realm of TMDs. The fundamental science behind plasma processing and modification of TMDs and their applications in different fields are presented and discussed. Future perspectives and challenges are highlighted to demonstrate the prominence of TMDs and the importance of surface engineering in next-generation optoelectronic applications.

A highly sensitive ion-selective chemiresistive sensor for online monitoring of lead ions in water.

Dissolved lead is a serious but common health hazard in drinking water, yet there is still no practical way to monitor its levels continuously in the distribution system or at the point of use. Here we propose using a lead-selective membrane on top of a chemiresistive device to continuously measure Pb2+ ion concentrations in real time. The detection limit was lowered by stabilizing the surface of the resistive film with sodium hydroxide and 15-crown-5 ether and optimizing the sensor geometry to maximize the effective surface area. The detection mechanism is based on the complexation of the Pb2+ ions by the lead ionophores within the membrane, thus modulating the interactions between the ionophores and the chemiresistive film. The limit of detection of the fabricated devices was reliably below 2 µg L-1, with concentrations up to 3 mg L-1 routinely quantifiable over several measurement cycles. The chemiresistive sensors can thus achieve lower detection limits than potentiometric devices while being more robust and simpler to fabricate by omitting the reference electrode. Ion-selective membrane-covered chemiresistors can therefore be deployed to continuously monitor drinking water sources and detect harmful levels of lead in real time.

An ion-selective chemiresistive platform as demonstrated for the detection of nitrogen species in water.

The use of ion-selective electrodes (ISE) is a well-established technique for the detection of ions in aqueous solutions but requires the use of a reference electrode. Here, we introduce a platform of ion-selective chemiresistors for the detection of nitrogen species in water as an alternative method without the need for reference electrodes. Chemiresistors have a sensitive surface that is prone to damage during operation in aqueous solutions. By applying a layer of ion-selective membrane to the surface of the chemiresistive device, the surface becomes protected and highly selective. We demonstrate both anion-selective (NO3-, NO2-) and cation-selective (NH4+) membranes. The nitrate sensors are able to measure nitrate ions in a range of 2.2-220 ppm with a detection limit of 0.3 ppm. The nitrite sensors respond between 67 ppb and 67 ppm of nitrite ions (64 ppb detection limit). The ammonium sensors can measure ammonium concentrations in a wide range from 10 ppb to 100 ppm (0.5 ppb detection limit). The fast responses to nitrate and nitrite are due to a mechanism involving electrostatic gating repulsion between negative charge carriers of the film and anions while ammonium detection arises from two mechanisms based on electrostatic gating repulsion and adsorption of ammonium ions at the surface of the p-doped chemiresistive film. The adsorption phenomenon slows down the recovery time of the ammonium sensor. This sensor design is a new platform to continuously monitor ions in industrial, domestic, and environmental water resources by robust chemiresistive devices.

A reagent-free phosphate chemiresistive sensor using carbon nanotubes functionalized with crystal violet.

Phosphate is important for plant and animal growth. Therefore, it is commonly added as a fertilizer in agricultural fields. Phosphorus is typically measured using colorimetric or electrochemical sensors. Colorimetric sensors suffer from a limited measuring range and toxic waste generation while electrochemical sensors suffer from long-term drifts due to reference electrodes. Here, we propose a solid-state, reagent-free and reference electrode-free chemiresistive sensor for measuring phosphate using single-walled carbon nanotubes functionalized with crystal violet. The functionalized sensor exhibited a measuring range from 0.1 mM to 10 mM at pH 8. No significant interference was observed for common interfering anions like nitrates, sulphates, and chlorides. This study showed a proof-of-concept chemiresistive sensor, which can potentially be used to measure phosphate levels in hydroponics and aquaponics systems. The dynamic measuring range further needs to be extended for surface water samples.

Tuning the Chemical and Mechanical Properties of Conductive MoS2 Thin Films by Surface Modification with Aryl Diazonium Salts.

Molybdenum disulfide (MoS2) is a promising material for applications in sensors, energy storage, energy conversion devices, solar cells, and fuel cells. Because many of those applications require conductive materials, we recently developed a method for preparing a conductive form of MoS2 (c-MoS2) using dilute aqueous hydrogen peroxide in a simple and safe way. Here, we investigate modulating the chemical and mechanical surface properties of c-MoS2 thin films using diazonium chemistry. In addition to a direct passivation strategy of c-MoS2 with diazonium salts for electron-withdrawing groups, we also propose a novel in situ synthetic pathway for modification with electron-donating groups. The obtained results are examined by Raman spectroscopy and X-ray photoelectron spectroscopy. The degree of surface passivation of pristine and functionalized c-MoS2 films was tested by exposing them to aqueous solutions of different metal cations (Fe2+, Zn2+, Cu2+, and Co2+) and detecting the chemiresistive response. While pristine films were found to interact with several of the cations, modified films did not. We propose that a surface charge transfer mechanism is responsible for the chemiresistive response of the pristine films, while both modification routes succeeded at complete surface passivation. Functionalization was also found to lower the coefficient of friction for semiconducting 2H-MoS2, while all conductive materials (modified or not) also had lower coefficients of friction. This opens up a pathway to a palette of dry lubricant materials with improved chemical stability and tunable conductivity. Thus, both in situ and direct diazonium chemistries are powerful tools for tuning chemical and mechanical properties of conductive MoS2 for new devices and lubricants based on conductive MoS2.

Defect Engineering of Graphene to Modulate pH Response of Graphene Devices.

Graphene-based pH sensors are a robust, durable, sensitive, and scalable approach for the sensitive detection of pH in various environments. However, the mechanisms through which graphene responds to pH variations are not well-understood yet. This study provides a new look into the surface science of graphene-based pH sensors to address the existing gaps and inconsistencies among the literature concerning sensing response, the role of defects, and surface/solution interactions. Herein, we demonstrate the dependence of the sensing response on the defect density level of graphene, measured by Raman spectroscopy. At the crossover point (ID/IG = 0.35), two countervailing mechanisms balance each other out, separating two regions where either a surface defect induced (negative slope) or a double layer induced (positive slope) response dominates. For ratios above 0.35, the pH-dependent induction of charges at surface functional groups (both pH-sensitive and nonsensitive groups) dominates the device response. Below a ratio of 0.35, the response is dominated by the modulation of charge carriers in the graphene due to the electric double layer formed from the interaction between the graphene surface and the electrolyte solution. Selective functionalization of the surface was utilized to uncover the dominant acid-base interactions of carboxyl and amine groups at low pH while hydroxyl groups control the high pH range sensitivity. The overall pH-sensing characteristics of the graphene will be determined by the balance of these two mechanisms.

Metal Cation Detection in Drinking Water.

Maintaining a clean water supply is of utmost importance for human civilization. Human activities are putting an increasing strain on Earth's freshwater reserves and on the quality of available water on Earth. To ensure cleanliness and potability of water, sensors are required to monitor various water quality parameters in surface, ground, drinking, process, and waste water. One set of parameters with high importance is the presence of cations. Some cations can play a beneficial role in human biology, and others have detrimental effects. In this review, various lab-based and field-based methods of cation detection are discussed, and the uses of these methods for the monitoring of water are investigated for their selectivity and sensitivity. The cations chosen were barium, cadmium, chromium, copper, hardness (calcium, magnesium), lead, mercury, nickel, silver, uranium, and zinc. The methods investigated range from optical (absorbance/fluorescence) to electrical (potentiometry, voltammetry, chemiresistivity), mechanical (quartz crystal microbalance), and spectrometric (mass spectrometry). Emphasis is placed on recent developments in mobile sensing technologies, including for integration into microfluidics.

Clostridioides difficile infection is associated with differences in transcriptionally active microbial communities.

Clostridioides difficile infection (CDI) is responsible for around 300,000 hospitalizations yearly in the United States, with the associated monetary cost being billions of dollars. Gut microbiome dysbiosis is known to be important to CDI. To the best of our knowledge, metatranscriptomics (MT) has only been used to characterize gut microbiome composition and function in one prior study involving CDI patients. Therefore, we utilized MT to investigate differences in active community diversity and composition between CDI+ (n = 20) and CDI- (n = 19) samples with respect to microbial taxa and expressed genes. No significant (Kruskal-Wallis, p > 0.05) differences were detected for richness or evenness based on CDI status. However, clustering based on CDI status was significant for both active microbial taxa and expressed genes datasets (PERMANOVA, p ≤ 0.05). Furthermore, differential feature analysis revealed greater expression of the opportunistic pathogens Enterocloster bolteae and Ruminococcus gnavus in CDI+ compared to CDI- samples. When only fungal sequences were considered, the family Saccharomycetaceae expressed more genes in CDI-, while 31 other fungal taxa were identified as significantly (Kruskal-Wallis p ≤ 0.05, log(LDA) ≥ 2) associated with CDI+. We also detected a variety of genes and pathways that differed significantly (Kruskal-Wallis p ≤ 0.05, log(LDA) ≥ 2) based on CDI status. Notably, differential genes associated with biofilm formation were expressed by C. difficile. This provides evidence of another possible contributor to C. difficile's resistance to antibiotics and frequent recurrence in vivo. Furthermore, the greater number of CDI+ associated fungal taxa constitute additional evidence that the mycobiome is important to CDI pathogenesis. Future work will focus on establishing if C. difficile is actively producing biofilms during infection and if any specific fungal taxa are particularly influential in CDI.

Identification and Quantification of Aqueous Disinfectants Using an Array of Carbon Nanotube-Based Chemiresistors.

Disinfection of water is essential to prevent the growth of pathogens, but at high levels, it can cause harm to human health. Therefore, accurate monitoring of disinfectant concentrations in water is essential to ensure safe drinking water. The use of multiple disinfectants at different stages in water treatment plants makes it necessary to also identify the type and concentrations of all of the disinfectant species present. Here, we demonstrate an effective approach to identify and quantify multiple disinfectants (using the example of free chlorine and potassium permanganate) in water using single-walled carbon nanotube (SWCNT)-based reagent-free chemiresistive sensing arrays. Facile fabrication of chemiresistive devices makes them a popular choice for the implementation of sensor arrays. Our sensing array consists of functionalized and unfunctionalized (blank) SWCNT sensors to distinguish the disinfectants. The distinct responses from the different sensors at varying concentrations and pH can be fitted to the mathematical model of a Langmuir adsorption isotherm separately for each sensor. Blank and functionalized sensors respond through different mechanisms that result in varying responses that are concentration- and pH-dependent. Chemometric techniques such as principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA) were used to analyze the sensor data. PCA showed an excellent separation of the analytes over five different pHs (5.5, 6.5, 7.5, 8.5, and 9.5). PLS-DA provided excellent separability as well as good predictability with a Q2 of 94.26% and an R2 of 95.67% for the five pH regions of the two analytes. This proof-of-concept solid-state chemiresistive sensing array can be developed for specific disinfectants that are commonly used in water treatment plants and can be deployed in water distribution and monitoring facilities. We have demonstrated the applicability of chemiresistive devices in a sensor array format for the first time for aqueous disinfectant monitoring.

Detection of free chlorine in water using graphene-like carbon based chemiresistive sensors.

Free chlorine is the most commonly used water disinfectant. Measuring its concentration during and after water treatment is crucial to ensure its effectiveness. However, many of the existing methods do not allow for continuous on-line monitoring. Here we demonstrate a solid state chemiresistive sensor using graphene-like carbon (GLC) that overcomes that issue. GLC films that were either bare or non-covalently functionalized with the redox-active phenyl-capped aniline tetramer (PCAT) were successfully employed to quantify aqueous free chlorine, although functionalized devices showed better performance. The response of the sensors to increasing concentrations of free chlorine followed a Langmuir adsorption isotherm in the two tested ranges: 0.01-0.2 ppm and 0.2-1.4 ppm. The limit of detection was estimated to be 1 ppb, permitting the detection of breaches in chlorine filters. The devices respond to decreasing levels of free chlorine without the need for a reset, allowing for the continuous monitoring of fluctuations in the concentration. The maximum sensor response and saturation concentration were found to depend on the thickness of the GLC film. Hence, the sensitivity and dynamic range of the sensors can be tailored to different applications by adjusting the thickness of the films. Tap water samples from a residential area were tested using these sensors, which showed good agreement with standard colorimetric measurement methods. The devices did not suffer from interferences in the presence of ions commonly found in drinking water. Overall, these sensors are a cost-effective option for the continuous automated monitoring of free chlorine in drinking water.

Defect Density-Dependent pH Response of Graphene Derivatives: Towards the Development of pH-Sensitive Graphene Oxide Devices.

In this study, we demonstrate that a highly pH-sensitive substrate could be fabricated by controlling the type and defect density of graphene derivatives. Nanomaterials from single-layer graphene resembling a defect-free structure to few-layer graphene and graphene oxide with high defect density were used to demonstrate the pH-sensing mechanisms of graphene. We show the presence of three competing mechanisms of pH sensitivity, including the availability of functional groups, the electrochemical double layer, and the ion trapping that determines the overall pH response. The graphene surface was selectively functionalized with hydroxyl, amine, and carboxyl groups to understand the role and density of the graphene pH-sensitive functional groups. Later, we establish the development of highly pH-sensitive graphene oxide by controlling its defect density. This research opens a new avenue for integrating micro-nano-sized pH sensors based on graphene derivatives into next-generation sensing platforms.

Facile fabrication of conductive MoS2 thin films by sonication in hot water and evaluation of their electrocatalytic performance in the hydrogen evolution reaction.

Molybdenum disulfide (MoS2) has long been used in catalysis and is a promising material for energy conversion devices. In order to utilize MoS2 in electrocatalytic applications, it needs to be sufficiently conductive. Even though a metallic 1T phase of MoS2 exists, its exfoliation process is expensive and difficult to scale because it involves hazardous materials and procedures, limiting its practical applications. We have previously reported an efficient and environmentally friendly procedure to exfoliate conductive MoS2 via sonication in very dilute aqueous hydrogen peroxide. Here, we report a new way of exfoliating heavily doped conductive MoS2 by sonication in pure water at 60 °C without additives. Conductivity measurements, Raman spectroscopy and X-ray photoelectron spectroscopy demonstrate that controlling the sonication time and temperature lead to the generation of small quantities of hydrogen peroxide in the water that interact with MoS2 to form a small amount of sub-stoichiometric MoO3-y . This impurity acts as a dopant and is responsible for the increase in conductivity of the MoS2 films without compromising their structural integrity. We also evaluate the performance of the doped MoS2 films as electrocatalysts in the hydrogen evolution reaction. We elucidate the mechanistic origin of the catalytic properties of these materials which may be of future use to develop a family of electrocatalysts based on doped MoS2.

Cause and consequence of carbon nanotube doping in water and aqueous media.

To utilize carbon nanotubes in real-world applications, we have to master their chemistry. At present there is a lack of understanding regarding what happens during basic manipulations, such as doping with acids, forming suspensions by sonication in water with surfactants, or detecting peroxides. We show that sonication of nanotubes in water leads to the in situ formation of molecular oxygen, causing doping, which can be quenched with ethanol. In the presence of the anionic surfactant sodium dodecyl sulfate, oxygen doping is overshadowed by doping due to the sulfate group. Stable suspensions of undoped nanotubes can be created with Triton-X spiked with ethanol. Hydrogen peroxide does not dope, but in high concentrations or in the presence of catalytic iron nanoparticles it decomposes to yield oxygen, which may dope. Hydrochloric acid does not dope, unlike sulfuric acid. Our results clarify the origins of doping while processing carbon nanotubes in water.

Solid State Sensors for Hydrogen Peroxide Detection.

Hydrogen peroxide (H2O2) is a key molecule in numerous physiological, industrial, and environmental processes. H2O2 is monitored using various methods like colorimetry, luminescence, fluorescence, and electrochemical methods. Here, we aim to provide a comprehensive review of solid state sensors to monitor H2O2. The review covers three categories of sensors: chemiresistive, conductometric, and field effect transistors. A brief description of the sensing mechanisms of these sensors has been provided. All three sensor types are evaluated based on the sensing parameters like sensitivity, limit of detection, measuring range and response time. We highlight those sensors which have advanced the field by using innovative materials or sensor fabrication techniques. Finally, we discuss the limitations of current solid state sensors and the future directions for research and development in this exciting area.

To dope or not to dope: the effect of sonicating single-wall carbon nanotubes in common laboratory solvents on their electronic structure.

Single-wall carbon nanotubes (SWCNTs) are commonly dispersed via sonication in a solvent prior to functionalization. We show that solvents such as dichloromethane, chloroform, 1,2-dichloroethane, and o-dichlorobenzene lead to an upward shift in the Raman response of the SWCNTs. We have used o-dichlorobenzene as a model molecule to explain this effect, and an upward shift of 9 cm(-1) is observed in the D* band. This blue shift is associated with p-type doping and is triggered only when the nanotubes are sonicated in the solvent. Sonication decomposes the chlorinated solvents, and new species (Cl2 and HCl(g)) are formed. The catalytic Fe nanoparticles inherently present in the nanotubes are etched by chlorine and hydrogen chloride to form iron chlorides during sonication in the solvent. The dopant was identified by X-ray photoelectron spectroscopy. With such knowledge of doping, the choice of solvent becomes crucial for any chemical reaction and can be intentionally tuned to produce SWCNTs films for electronics applications.

Robust Chemiresistive Sensor for Continuous Monitoring of Free Chlorine Using Graphene-like Carbon.

Free chlorine is widely used in industry as a bleaching and oxidizing agent. Its concentration is tightly monitored to avoid environmental contamination and deleterious human health effects. Here, we demonstrate a solid state chemiresistive sensor using graphene like carbon (GLC) to detect free chlorine in water. A 15-20 nm thick GLC layer on a PET substrate was modified with a redox-active aniline oligomer (phenyl-capped aniline tetramer, PCAT) to increase sensitivity, improve selectivity, and impart fouling resistance. Both the bare GLC sensor and the PCAT-modified GLC sensor can detect free chlorine continuously and, unlike previous chemiresistive sensors, do not require a reset. The PCAT-modified sensor showed a linear response with a slope of 13.89 (mg/L)-1 to free chlorine concentrations between 0.2 and 0.8 mg/L which is relevant for free chlorine monitoring for drinking water and wastewater applications. The PCAT-modified GLC sensors were found to be selective and showed less than 0.5% change in current in response to species such as nitrates, phosphates and sulfates in water. They also were resistant to fouling from organic material and showed only a 2% loss in signal. Tap water samples from residential area were tested using this sensor which showed good agreement with standard colorimetric measurement methods. The GLC and PCAT-GLC sensors show high sensitivity and excellent selectivity to free chlorine and can be used for continuous automated monitoring of free chlorine.

Reagent-Free Quantification of Aqueous Free Chlorine via Electrical Readout of Colorimetrically Functionalized Pencil Lines.

Colorimetric methods are commonly used to quantify free chlorine in drinking water. However, these methods are not suitable for reagent-free, continuous, and autonomous applications. Here, we demonstrate how functionalization of a pencil-drawn film with phenyl-capped aniline tetramer (PCAT) can be used for quantitative electric readout of free chlorine concentrations. The functionalized film can be implemented in a simple fluidic device for continuous sensing of aqueous free chlorine concentrations. The sensor is selective to free chlorine and can undergo a reagent-free reset for further measurements. Our sensor is superior to electrochemical methods in that it does not require a reference electrode. It is capable of quantification of free chlorine in the range of 0.1-12 ppm with higher precision than colorimetric (absorptivity) methods. The interactions of PCAT with the pencil-drawn film upon exposure to hypochlorite were characterized spectroscopically. A previously reported detection mechanism relied on the measurement of a baseline shift to quantify free chlorine concentrations. The new method demonstrated here measures initial spike size upon exposure to free chlorine. It relies on a fast charge built up on the sensor film due to intermittent PCAT salt formation. It has the advantage of being significantly faster than the measurement of baseline shift, but it cannot be used to detect gradual changes in free chlorine concentration without the use of frequent reset pulses. The stability of PCAT was examined in the presence of free chlorine as a function of pH. While most ions commonly present in drinking water do not interfere with the free chlorine detection, other oxidants may contribute to the signal. Our sensor is easy to fabricate and robust, operates reagent-free, and has very low power requirements and is thus suitable for remote deployment.

Correction: Fibrin Sealants in Dura Sealing: A Systematic Literature Review.

[This corrects the article DOI: 10.1371/journal.pone.0151533.].

Resource utilization and costs of blood management services associated with knee and hip surgeries in US hospitals.

This article assesses the use and costs of blood transfusion during knee and hip surgery through a retrospective observational study of 92,223 discharged inpatients who had undergone knee or hip surgery from July 1, 2003, through June 30, 2004; a sample of US hospitals that participated in the Perspective Comparative Database (Premier Inc., Charlotte, NC) was used. Descriptive and multivariate analyses were performed to determine the use and costs of allogeneic blood transfusion (ABT). The average cost of ABT per user ranged from $387 (SD=$952) for red blood cells to $6585 (SD=$11,162) for cryoprecipitate. Utilization rates in the sample were as follows: antifibrinolytics, 0.14%; topical sealants, 3.24%; volume expanders, 3.89%; erythropoietin agents, 5.08%; and hypotensive anesthesia, 22.28%. Patients who were given volume expanders ($133.73, SD=$23.00, P<.01) or erythropoietin ($177.72, SD=$34.61, P<.01) had higher costs associated with ABT than did those who did not use volume expanders or erythropoietin. Patients who received hypotensive anesthesia (odds ratio [OR]=1.96; 95% confidence interval [CI], 1.87-2.06), a volume expander (OR=1.71; 95% CI, 1.57- 1.85), a topical sealant (OR=1.61; 95% CI, 1.45-1.79), or an erythropoietic agent (OR=2.30; 95% CI, 2.06-2.57) had a greater likelihood of ABT. Investigators concluded that most transfusion reduction techniques are underused, or they do not reduce the burden of ABT associated with knee or hip surgery.

Fibrin Sealants in Dura Sealing: A Systematic Literature Review.

BACKGROUND: Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. METHODS: A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. RESULTS: A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. CONCLUSIONS: A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety.