DOI:
10.1039/C6RA24349E
(Review Article)
RSC Adv., 2016,
6, 110775-110788
Graphene quantum dots: recent progress in preparation and fluorescence sensing applications
Received
30th September 2016
, Accepted 17th November 2016
First published on 17th November 2016
Abstract
Fluorescent graphene quantum dots (GQDs) have attracted tremendous attention because of their unique 2D layered structure, large surface area, good water solubility, tunable fluorescence, high photostability, excellent biocompatibility and low toxicity, which make them promising candidates for applications in various fields. In this review, we summarize the latest progress in research on GQDs, focusing on their preparation via both top-down and bottom-up routes and application in fluorescence sensing of inorganic ions, organic molecules and biomaterials. This review provides insight into GQDs to inspire their further development, including their controllable preparation and use in a wider range of sensing applications, by the large community of researchers focusing on graphene.
 Shenghai Zhou | Shenghai Zhou received his Ph.D. in analytical chemistry (2013) from Jilin University of China. After working at the Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, he is now working at College of Chemistry and Chemical Engineering, Hebei Normal University for Nationalities. He is mainly engaged in the research of carbon and copper-based chemical sensor. |
 Qunhui Yuan | Qunhui Yuan works in the School of Materials Science and Engineering in Harbin Institute of Technology (Shenzhen) as a professor since 2016, after her working in the Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences (CAS). She received her Ph.D. in the Institute of Chemistry (CAS) and fulfilled her postdoctoral research in Clarkson University and Temple University in U.S. Her research interests is to reveal the environmental related problems, including investigation on the nanoscaled processes/reactions at surfaces/interfaces and development of sensors for environmental hazards, by using techniques such as scanning probe microscopy, electrochemistry and fluorescence spectroscopy. |
1. Introduction
Graphene quantum dots (GQDs) consisting of two dimensional graphene sheets with lateral dimensions less than 100 nm in single, double or a few (3–10) layers have attracted tremendous attention.1,2 They are different from the spherical photoluminescent carbon nanodots within 10 nm in diameter, which are generally divided into carbon quantum dots (CQDs) with crystal lattices and carbon nanoparticles without crystalline structures.3 Compared with the above mentioned carbon nanodots, their cousin GQDs possess excellent physical and chemical properties, such as higher surface area, larger length-to-diameter ratio and better surface grafting via the π–π conjugated network because of their structural graphene layers. GQDs possess not only intriguing properties of the graphene,4–7 but also improved solubility and extended fluorescence compared with those of larger graphene sheets.2,8 Interestingly, as a new family member of the fluorescent materials, GQDs display many merits, such as lower toxicity, better resistance to photo bleaching and better biocompatibility, compared with commercial organic dyes and traditional semiconductor quantum dots (for example, CdS and CdTe).9 Therefore, fluorescent GQDs with unique structure and properties provide an unprecedented opportunity to improve the performance of organic light-emitting diodes, fuel cells, bioimaging and so on.8–11 Of particular interest is the recent finding that GQDs can be used as fluorescent sensing probes to detect inorganic ions, small organic molecules and large biomaterials.2,12 This is because (a) the high photostability of GQDs guarantees the stability of the fluorescence signal, which can ensure the accuracy of the detection results; (b) qualitative detection of an analyte can be easily achieved by simply monitoring the variation of the fluorescence intensity of GQDs without the need for expensive instruments, time-consuming operations and complicated sample pretreatment; and (c) their low toxicity and good biocompatibility make GQDs safe for humans and the environment. Therefore, GQD-based fluorescent probes are promising candidates for analyte detection, and many studies on this topic are emerging at present.
Some noteworthy review articles focusing on the basic properties,1,8 fluorescence mechanism3 and applications of GQDs in energy, environmental and biological fields have already been published.1,2,8–10,12 In addition, reviews that mainly consider the preparation of GQDs emerged in 2012,8 2013,1,13 2014
9 and 2015.2 However, the very rapid development of the GQD research field means that various new strategies for their preparation are continuously being published. Therefore, an updated review on the latest advances, especially those regarding the preparation of GQDs, is needed. Furthermore, with the development of various novel methods to prepare GQDs, they have also been used as fluorescent probes to detect numerous new targets. Based on these considerations, we mainly focus on recent progress in the field of GQDs in this review with an emphasis on the preparation of GQDs and their fluorescent sensing applications including simple detection of inorganic ions, small organic molecules and large biomaterials are briefly summarised. We hope this article will offer valuable insight to facilitate the investigation of GQDs and stimulate new ideas for further research.
2. Synthesis of GQDs
Various novel methods to prepare fluorescent GQDs have been developed with the purpose of realising simple, effective, size-controllable or high-yield synthetic methods to obtain high-quality GQDs. Generally, the syntheses of GQDs can be divided into two main categories, top-down and bottom-up synthetic approaches, based on the relationship between the source and product.1,8 Top-down strategies involve directly cleaving bulk carbon materials into nanoscale GQDs via physical, chemical or electrochemical techniques.9,13 Conversely, bottom-up methods are growth strategies; namely, appropriate molecular precursors gradually grow into nanosized GQDs by applying external energy.
2.1 Top-down routes
A variety of bulk carbon materials including graphite,14 graphene,15 carbon nanotubes (CNTs),16 coal,17 carbon nanofibers,18 carbon black,19 neem leaf derived carbon,20 carbon nano-onions,21 C60,22 activated carbon powder23 and, recently, rice husk-derived carbon,24 have been used as raw materials to prepare GQDs by top-down methods. Heteroatom-doped bulk carbon materials such as adenosine triphosphate-derived carbon containing N and P,25 metal–organic framework-derived carbon with N,26 porous polythiophene-derived carbon with S27 and fluorinated graphene oxide (FGO)28 have also been used to produce corresponding heteroatom-doped GQDs with excellent performance. These precursors are usually subjected to chemical/electrochemical oxidation, hydrothermal/solvothermal treatment, laser ablation method, microwave or ultrasound assisted treatment to obtain GQDs.1,8,29,30 Top-down strategies can achieve large-scale production of GQDs with numerous surface functional groups via relatively simple operations.8,9
2.1.1 Chemical oxidation. Chemical oxidation, namely, treating bulk carbon materials with an oxidative reagent, is a simple and effective approach for large-scale production of GQDs. Commonly used oxidative reagents include strong acids,18,31 powerful oxidants16 and mild oxidants.32,33 Among the oxidative reagents, strong acids are widely applied to prepare GQDs. As shown in Fig. 1a, Dong and co-workers first oxidized single-walled carbon nanotubes (SWCNTs) with 8 M HNO3. Then, they hydrothermally heated the oxidized the SWCNTs in water at 200 °C, which led to complete destruction of the tubular structure of the SWCNTs and the formation of aggregated graphene nanosheets. They obtained two types of water-soluble single-layered GQDs with different degrees of oxidation by immersing the graphene nanosheets in 8 and 12 M HNO3. The two types of prepared GQDs displayed different optical properties, which was mainly attributed to their different degrees of oxidation.31
 |
| Fig. 1 (a) Diagram outlining the preparation of two types of GQDs from SWCNTs. (Reprinted with permission from ref. 31. Copyright 2013 Elsevier.) (b) Schematic diagram of the preparation of N-GQDs. (Reprinted with permission from ref. 26. Copyright 2015 Royal Society of Chemistry.) | |
Besides acidic oxidative reagents, powerful oxidants such as KMnO4 have been used to prepare GQDs. Kundu et al. chemically oxidized multi-walled carbon nanotubes (MWCNTs) in an acidic solution containing KMnO4 to prepare GQDs.16 The resultant GQDs were enriched with –COOH and –OH functional groups and possessed an average particle size of 12 nm within a size range of 10–15 nm. Although direct synthesis from bulk carbon materials using strong acids and powerful oxidants has advantages, a common problem is that it is difficult to thoroughly remove excess strong oxidant. In such a case, a complex purification process is needed, which can be inefficient. Thus, research on the preparation of GQDs using mild oxidants has recently appeared. For instance, Shin et al. heated several natural carbon resources (graphite, MWCNTs, carbon fiber (CF) and charcoal) at 200 °C in DMF using oxone as the oxidant, resulting in blue fluorescent GQDs.32 This novel acid-free approach does not require the neutralisation of strong acids, making it simple and eco-friendly.
Apparently, the current chemical oxidation methods used to prepare GQDs are chiefly based on chemical oxidation in the solution phase; namely, the oxidative reagent and bulk carbon material are usually in the same solution. Thus, these methods always need a large amount of oxidant and generally involve a tedious purification process. In this regard, we developed an efficient acid vapour cutting strategy to synthesize GQDs in which just 2 mL of concentrated HNO3 was used as “scissors” to cut metal–organic framework-derived carbon placed on a porous SiO2 grid without contact with HNO3 (see Fig. 1b).26 After the reaction, GQDs were easily and directly obtained by in situ filtration, while the unreacted residue was retained on the porous SiO2 grid. This method avoids complicated separation and purification processes and is low-cost, rapid and eco-friendly. Another group used the clean, mild oxidising agent H2O2 with the assistance of a tungsten oxide nanowire (W18O49) catalyst to oxidize and cleave graphene oxide (GO), leading to the formation of GQDs.33 The lateral size of the GQDs was controlled between 4 and 21 nm simply by changing the concentrations of W18O49 and H2O2. Furthermore, the reaction products were only H2O and GQDs, so the prepared GQD aqueous solution could be directly used for biological imaging without the need for further purification.
2.1.2 Electrochemical exfoliation. Electrochemical exfoliation has been widely used to prepare GQDs from CNTs,34 graphite rods,35,36 and graphene films15,37 with the help of high driving potential between electrodes. The varied fluorescence of GQDs can also be obtained, ranging from blue to red via electrochemical methods.34–36,38 Generally, electrochemical exfoliation can be classified based on the electrolyte used: water-phase electrooxidation and organic-phase electrooxidation. In water-phase electrooxidation, a high redox potential can oxidize water to generate OH˙ and O˙ radicals that act as electrochemical “scissors” to release GQDs from the carbon-based reagent.35 In organic-phase electrooxidation, the exfoliation process has been attributed to (a) the electrical stress and (b) the ability of the electrolyte anions (such as PF6−) to intercalate between graphene layers.37 As an example of water-phase electrooxidation synthesis of GQDs, Qu's group gave the first demonstration.15 In their study, a hydrophilic graphene film was initially obtained by filtration, which was then treated with O2 plasma. The graphene film, as the working electrode, was then oxidized by cyclic voltammetry (CV) in the potential range of −3.0–+3.0 V in 0.1 M phosphate-buffered aqueous solution to prepare GQDs. The obtained GQDs possessed a uniform size of 3–5 nm and exhibited green luminescence. By selecting a proper electrolyte, heteroatom-doped GQDs with promising properties can be obtained easily by electrochemical methods, usually requiring only one step. For instance, Li et al. reported an electrochemical synthesis of S-GQDs at a constant electrolysis voltage of 5 V using a graphite rod as the working electrode and 0.1 M sodium p-toluenesulfonate aqueous solution as the electrolyte.36 These S-GQDs had a relatively narrow size distribution ranging from 2 to 4 nm with an average diameter of 3 nm and a typical topographic height of 0.3–1.2 nm with an average height of 0.7 nm (single or bilayer).Regarding organic-phase synthesis of GQDs, Li and co-workers electrochemically cleaved a graphene film into N-doped GQDs using CV at a scan rate of 0.5 V s−1 in an organic electrolyte consisting of acetonitrile and nitrogen-rich tetrabutylammonium perchlorate.39 The as-prepared N-doped GQDs with a N/C atomic ratio of approximately 4.3% possessed diameters of around 2–5 nm and a typical topographic height of 1–2.5 nm (ca. 1–5 graphene layers). These GQDs remained homogeneous for a long period and exhibited electrocatalytic activity in the oxygen reduction reaction. Ananthanarayanan et al. prepared GQDs by electrooxidation of 3D porous graphene immersed in an organic electrolyte of 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6) and acetonitrile.37 The prepared GQDs possessed high crystallinity and uniform lateral size (∼3 nm) and thickness (mostly single-layered).
2.1.3 Hydrothermal/solvothermal treatment. Hydrothermal cutting to prepare GQDs involves heating bulk water-soluble carbon materials (such as graphene with high oxygen content) in water at high temperature and pressure in a closed autoclave, while solvothermal treatment usually uses organic solvents instead of water.40–42 Pan and co-workers reported the first hydrothermal synthesis of fluorescent GQDs.40 In their method, disordered GSs were first synthesized by thermally reducing monolayer GO. Then, the as-prepared GSs were oxidized in concentrated H2SO4 and HNO3 solution under ultrasonication to introduce oxygen-containing functional groups onto the carbon lattice as cleavage sites. Finally, the hydrothermal deoxidization of the oxidised GSs into GQDs was performed at 200 °C for 10 h under weakly alkaline conditions (pH = 8). The obtained GQDs displayed diameters of 5–13 nm with an average diameter of 9.6 nm and topographic heights of 1–2 nm (1–3 graphene layers).Interestingly, when adding chemicals with heteroatoms into the aqueous solutions, doped GQDs can be obtained by simple one-step hydrothermal treatment. Recently, Zhang and colleagues prepared a homogeneous solution containing GO, ammonia solution and powdered S.41 They transferred the mixture into an autoclave where it was heated at 180 °C for 12 h. After filtration and dialysis, N,S co-doped GQDs were obtained. By changing the amount of S added, the fluorescence intensity of the N,S-GQDs could be adjusted.
As an example of GQDs produced using a solvothermal route, Zhu et al. prepared GQDs with strong green fluorescence and high quantum yields of 11.4% by solvothermal treatment of GO (270 mg) in DMF (10 mL) at 200 °C for 5 h.42 The average diameter and height of the as-prepared GQDs were 5.3 and 1.2 nm, respectively, indicating that most of the GQDs were single- or bilayered.
2.1.4 Microwave/ultrasound assisted methods. Unlike electrochemical oxidation, acidic oxidation and hydrothermal GQD formation methods usually require a heating source for the reaction. However, traditional heating sources like electric ovens and oil baths result in time-consuming procedures. Thus, some high-energy technologies, including microwave and ultrasound assisted routes, have recently been used to develop fast synthetic routes to GQDs.43,44 Microwave irradiation can offer rapid and uniform heat energy to a reaction medium, allowing the reaction time to be dramatically shortened. On this ground, bulk carbon materials, including GO,43 graphite,45 carbon black46 and MWCNTs,47 have been used for the microwave-assisted synthesis of GQDs. In 2012, Li et al. reported the first microwave-assisted synthesis of GQDs with green and blue fluorescence in an acidic environment.43 They used GO as the graphene source and microwave radiation as the source of heat. Fig. 2a depicts the formation of green and blue GQDs. The GO precursor was prone to fracture because of the presence of epoxy lines on the carbon lattice formed via acid oxidation, which were considered to be the oxidation active sites for the formation of GQDs. The as-prepared GQDs were uniform and monodisperse, exhibiting an average diameter of 3 nm and topographic height of <0.7 nm (single layer).
 |
| Fig. 2 (a) Schematic representation of the preparation of blue and green GQDs. (Reprinted with permission from ref. 43. Copyright 2012 Wiley.) (b) Schematic illustration of a preparation strategy of GQDs. (Reprinted with permission from ref. 53. Copyright 2014 Wiley.) | |
Recently, the microwave assisted method has also been used to prepare GQDs doped with elements such as F,28 B48 and N,F and S.47 For example, Sun et al. used FGO as a raw material to prepare fluorinated GQDs.28 In their approach, FGO was added to a solution of concentrated HNO3/H2SO4 (4
:
1) and then exposed to microwave irradiation for 6 h in a microwave oven operating at a power of 650 W. Kundu et al. reported a facile, rapid synthesis of GQDs co-doped with N,F and S by microwave-irradiation treatment of MWCNTs in the commercial ionic liquid (IL) (1-methyl-1-propylpiperidinium bis(trifluoromethylsulfonyl)imide).47 The researchers first dispersed MWCNTs in the IL by ultrasonic treatment for 1 h. The resulting mixture was heated in a 1100 W microwave for 15 min. After filtration and dialysis, N,F,S-GQDs with an average size of 2 nm and high quantum yield of 70% were obtained. The ultrafast preparation and heteroatom doping of GQDs were attributed to the use of a microwave assisted technique and an IL that contained heteroatoms.
Recently, ultrasound assisted techniques have been used for the simple and mild synthesis of GQDs at room temperature. When a liquid is exposed to ultrasound, small vacuum bubbles constantly form and abruptly collapse, which results in high-speed liquid jets, deagglomeration and strong hydrodynamic shear forces that break down carbon materials.49 Zhuo and co-workers developed a direct, facile ultrasonic assisted method to prepare GQDs from graphene in aqueous solution in 2012.44 Since then, bulk carbon materials such as GO,50 carbon nanofibers,51 MWCNTs,52 and cheap graphite53 have been investigated as starting materials for the synthesis of GQDs using ultrasound in aqueous solution44,50,53 or organic solvents.51,54 Routh et al. reported a new method to synthesise GQDs from GO via a sono-Fenton reaction strategy; that is, the Fenton reaction under sonication conditions.50 In their strategy, GO was dissolved in deionised water, followed by the addition of H2O2 and FeCl3. After stirring, the mixture was sonicated for 4 h to form GQDs. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) of the resulting GQDs revealed their good dispersion, diameter of ∼5.6 ± 1.4 nm size and height of 0.2–5 nm. Song and colleagues prepared GQDs using graphite as a raw material with the aid of ultrasound (Fig. 2b).53 In their experiment, graphite and potassium sodium tartrate with a mass fraction ratio of 1
:
10 were mixed and ground. The ground homogeneous mixture was heated in an autoclave at 250 °C for 24 h to prepare graphite intercalation compounds (GICs). After the formation of GICs, they were dispersed in water and sonicated for 1 h to prepare GQDs. The diameters of the GQDs were mainly distributed in the range of 1–5 nm and their heights were 0.5–1.5 nm. Interestingly, heteroatom-doped GQDs can also be fabricated by ultrasound-assisted methods. Zhao et al. prepared chlorine-doped GQDs (Cl-GQDs) by using chlorinated carbon fiber as a starting material in the organic solvent N-methylpyrrolidone with the help of ultrasound.51 CFs derived from degreasing cotton were chlorinated with HCl, resulting in the introduction of halogen and oxygen functional groups into the layered structure of the CFs. In this chlorination process, HCl acts not only as a Cl doping source but also exfoliates the CFs into small pieces. The chlorinated CFs were then added into N-methylpyrrolidone and sonicated for 10 h to prepare GQDs. The group found that the presence of Cl-GQDs substantially enhanced the performance of photovoltaic photodetectors.
2.1.5 Other trials to fabricate GQDs. The promising properties of GQDs have prompted researchers to develop new methods for their simple and effective synthesis. Li et al.1 and Zhang et al.8 have reviewed the photo-Fenton reaction strategy, nanolithography and nanotomy assisted exfoliation. In this section, we describe a recently reported strategy to fabricate GQDs.As shown in Fig. 3, Zhu and co-workers have developed a novel, facile and eco-friendly magnetron sputtering method to prepare monodisperse GQDs directly from graphite.55 In their method, graphite and ZnO powder were first mixed uniformly and pressed into a composite target using a pressure of 30 MPa. The composite target was calcined at 1100 °C for 4 h in nitrogen to prepare a carbon source. Second, silicon plates were washed with acetone, methanol and water and then dried with a nitrogen stream to receive the GQDs. Third, magnetron sputtering was performed using a target-to-substrate distance of 100 mm, base pressure of 1 × 10−4 mTorr, working pressure of 0.55 mTorr, sputtering power of 40 W and deposition time of 30 min. Finally, the silicon plates with GQDs and ZnO were sonicated for 15 min in HCl to remove ZnO and obtain GQDs. The as-prepared GQDs possessed good dispersion and size uniformity with a diameter of 4–12 nm and thickness of 1–2 nm.
 |
| Fig. 3 Schematic diagram of one-step fabrication of a GQD/ZnO composite film via magnetron sputtering and subsequent isolation of GQDs through acid treatment and dialysis. (Reprinted with permission from ref. 55. Copyright 2015 Elsevier.) | |
Xu et al. developed another approach to synthesise GQDs involving non-selective top-down cleavage of a bulk carbon precursor.56 Their approach of nanoreactor-confined synthesis and in situ filtration using a recyclable ordered mesoporous SiO2 (SBA-15) template produced GQDs that displayed yellow luminescence. An ordered mesoporous carbon replica of SiO2, namely C–SiO2, was first prepared by a nanocasting strategy in which SBA-15 was used as a template. Then, C–SiO2 powder was placed on a porous SiO2 grid and heated in an autoclave containing 2 mL of concentrated HNO3. After heating at 160 °C for 5 h, GQDs formed because the acid vapour cleaved the C–SiO2 composite in its confined mesopores. The large surface area and confined pores of the C–SiO2 nanocomposite resulted in the formation of GQDs with a narrow size distribution. Finally, the GQDs were obtained by in situ filtration. The as-prepared GQDs exhibited a relatively narrow size distribution ranging from 2.5 to 5.2 nm with an average diameter of ca. 3.6 nm and thickness of less than 2 nm.
2.2 Bottom-up routes
Recently, the number of bottom-up methods to prepare GQDs has been growing because these methods with good controllability can produce GQDs with well-defined sizes, shapes and properties. The main bottom-up methods include carbonisation of organic precursors,57–68 stepwise organic synthesis,69,70 chemical vapour deposition (CVD),71,72 and high-pressure and -temperature strategies.73–75
2.2.1 Carbonization of organic precursors. Among the above-mentioned bottom-up methods, the carbonization of organic precursors has been widely used to synthesize GQDs because of its simplicity. The main GQD precursors used in this approach include citric acid,63 carbohydrate (glucose or sucrose),62 amino acids,64 acetylacetone,65 ethanolamine57 and humic acid.66 By proper selection of the precursors, the heteroatoms doped GQDs such as N-GQDs,57,67,68,76 Cl-GQDs,59 S-GQDs,58 N,S-GQDs60,61 and N,O-GQDs77 can be fabricated. For instances, Wang's group prepared a highly fluorescent N-GQD by using ammonium citrate as both nitrogen and carbon precursor via a direct carbonization of ammonium citrate under atmospheric pressure.67 In their study, a homogeneous ammonium citrate solution was first prepared and then heated at 200 °C to let the N-GQDs form. Li et al. developed a kind of Cl-GQDs with a size of 5.4 nm containing 2 at% Cl via a facile hydrothermal method by using fructose and HCl as carbon and chlorine sources, respectively.59 Under hydrothermal condition, H and O from fructose may dehydrate, leaving behind carbon to form the nucleus of GQD. HCl catalyses the reaction and provides S-dopant. Following similar design conception, heteroatoms co-doped GQDs were synthesized via the carbonization of organic precursors. For example, Qu and colleagues reported a preparation of N,S-GQDs in 2014 with citric acid as the carbon source and thiourea as the N and S source, respectively.61 In their study, the citric acid and thiourea were dissolved into DMF and heated to 180 °C in a heating mantle. After centrifugation, GQDs with a lateral dimension of about 4.5 nm and thickness of 1 nm were obtained. Interestingly, the as-obtained N,S-GQDs emit three primary colors independently at three excitation wavelengths, under excitations of 340–420 nm, 460–540 nm, and 560–620 nm, respectively. This may be because the doping with S and N change the chemical environment of the GQDs. With the growing emergence of B-CQDs, Si-CQDs, P-CQDs, and so on, based on the carbonization of organic precursors,78–82 some interesting heteroatom doped GQDs such as B-GQDs, Si-GQDs, P-GQDs etc. may be expected via this strategy.
2.2.2 Stepwise organic synthesis of GQDs. Stepwise organic synthesis provides an opportunity to prepare well-defined, uniform GQDs. Yan and co-workers synthesised three sizes of large colloidal GQDs using 4-bromo-3-iodoaniline as a starting material by a solution chemistry route.69 The three GQDs were all stabilized by multiple 2′,4′,6′-trialkyl phenyl groups and made up of 168, 132 and 170 conjugated carbon atoms, achieving regulation of GQD size. Later, the same group used a solution chemistry approach to prepare N-GQDs with well-defined structures.70 In this work, they first prepared a nitrogen-containing intermediate using small substituted benzene derivatives such as 2-bromo-5-iodo-3′-(phenylethynyl)-1,1′-biphenyl and phenylboronic acid as starting materials. The nitrogen-containing intermediate underwent double Suzuki cross-coupling reactions to result in the precursor of GQDs. Finally, N-GQDs were obtained by treating the precursor with a large excess of iron(III) chloride under a constant stream of argon in a dichloromethane/nitromethane mixture. The as-prepared N-GQDs showed excellent electrocatalytic activity in the oxygen reduction reaction.
2.2.3 Chemical vapour deposition. It is well known that 2D graphene can be prepared by CVD. When the nucleation rate of graphene exceeds its growth rate (by tuning the substrate surface morphology, temperature and growth time as well as the flow rates of the carbon source and hydrogen), the size of the graphene materials formed can be decreased.71,72 Fan et al. first prepared GQDs by CVD using metal copper foil as the substrate and methane as the carbon source.71 In their preparation process, polycrystalline copper foil was cleaned with HCl and alcohol to remove the oxidized surface layer. The copper foil was then placed into a furnace and heated to 1000 °C in a mixture of argon and hydrogen at flow rates of 200 and 10 mL min−1, respectively. After 40 min, the flow of hydrogen gas was stopped while the argon flow was continued for another 10 min to remove residual hydrogen in the reaction tube. Methane gas was turned on at a flow rate of 2 mL min−1 for 3 s and then the copper was quickly taken out from the heating zone and cooled down in the argon environment. The as-prepared GQDs possessed a diameter of 5–15 nm and height of 1–3 nm. Later, Xuli Ding demonstrated the preparation of GQDs on hexagonal boron nitride substrates without any metal catalyst.72 By adjusting the gas ratio (CH4
:
H2
:
Ar) and keeping the same reaction time, they synthesised GQDs with different numbers of graphene and thickness-dependent visible photoluminescence.
2.2.4 High-pressure and high-temperature method to prepare GQDs. Zhu et al. successfully prepared N-GQDs by a solid-to-solid process at high temperature (800–1200 °C) and pressure (4.0 GPa).73 They used a piston-cylinder apparatus with solid confining media as the solid reaction instrument. Melamine powder was placed into the instrument and then exposed to high pressure (4.0 GPa) increasing at a rate of 0.2 GPa h−1 and high temperature (800–1200 °C) with a heating rate of 100 °C h−1. After lowering the reaction pressure and temperature back to room pressure and temperature, N-GQDs were obtained in a high yield of ∼63 wt%. TEM images showed fairly uniform N-GQDs with a diameter of ca. 2–6 nm, while AFM data revealed a typical topographic height of 1–1.5 nm. The N content of the GQDs could be tuned by changing the heating temperature.
2.2.5 Other bottom-up methods to prepare GQDs. Some interesting methods have recently been developed to obtain single-layered GQDs. For example, Li and co-workers reported a single-layered intermolecular carbonisation method to synthesize single-layered N-GQDs using 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) as a N-containing organic precursor that is inherently arranged in a 2D plane.74 TATB powder was heated to 750 °C for 20 min in a N2 atmosphere at a heating rate of 2 °C min−1. In this process, TATB planar sheets were converted into N-GQD agglomerates, which consist of abundant GSs with weak interactions between them. N-GQDs were obtained by ultrasonic treating the resulted N-GQD agglomerates for 2 h and stirring in a mixture of concentrated H2SO4 (60 mL) and HNO3 (20 mL). TEM and AFM measurements showed that the N-GQDs possessed a small size of 2–5 nm and 80% of the exfoliated N-GQDs were single layered sheet.Another group successfully prepared single-layered GQDs by hydrothermal treatment of citrate confined in 2D layered double hydroxides (LDHs).75 Citrate–intercalated Mg–Al-LDHs (Mg–Al–citrate-LDHs) were prepared by co-precipitation using Mg(NO3)2·6H2O, Al(NO3)3·9H2O, citrate and NaOH as raw materials. The solution of Mg–Al–citrate-LDHs and ammonia was reacted at 180 °C for 8 h in an autoclave, resulting in the formation of Mg–Al-GQD-LDHs. Finally, the GQDs were isolated by dissolving the Mg–Al-LDHs with HCl. The GQDs obtained by this strategy showed a small lateral size of 2.2 ± 0.2 nm and the average height of most GQDs (>90%) was 0.7 nm. Fig. 4 depicts the overall procedure to prepare GQDs using LDHs.
 |
| Fig. 4 Schematic illustration of the formation of S-GQDs in the confined space of layered double hydroxides. (Reprinted with permission from ref. 75. Copyright 2015 Royal Society of Chemistry.) | |
2.3 Quantum yield
Quantum yield (QY), an important factor for fluorescence sensing application, may vary with the synthesis method and the surface chemical environment of the GQDs, ranging from 2% to 86%.25,35,41,47,73,83,84 As shown in Table 1, the lowest QY of 2% is observed in GQDs prepared via stepwise organic synthesis while the highest QY of 86% for GQDs is obtained with a bottom-up process involving high pressure and temperature. Considering the rich structural oxygen-containing groups on the GQDs, the treatment containing reduction or surface passivation is generally to be applied to GQDs to deactivate those oxygen-containing groups in order to get higher QYs since the structural oxygen-containing groups are acting as the non-radiative electron–hole recombination centers.43,85 For example, Li et al.43 obtained greenish-yellow GQDs with QY of 11.7% by using microwave-assisted acidic oxidation strategy. Then the QY was further improved to 22.9% by a gentle reduction of GQDs with NaBH4. Tetsuka et al.85 synthesized amino-functionalized GQDs (af-GQDs) with high QY of 29% via hydrothermally cutting graphene sheets in ammonia solution. Subsequently, the af-GQDs were passivated by polyethylene glycol, which significantly enhanced the QY to 46%.
Table 1 A brief summary of the quantum yield of GQDs synthesized via typical synthetic methods
Methods |
Sub classification |
Quantum yield (QY) |
Ref. |
Top-down |
Chemical oxidation |
27.5% |
25 |
Top-down |
Electrochemical exfoliation |
14% |
35 |
Top-down |
Hydrothermal/solvothermal treatment |
18.6% |
41 |
Top-down |
Microwave assisted method |
70% |
47 |
Bottom-up |
Carbonization of organic precursors |
78% |
83 |
Bottom-up |
Step organic synthesis of GQDs |
2% |
84 |
Bottom-up |
High pressure and high temperature |
86% |
73 |
3. Fluorescence sensing based on GQDs
The most important feature of GQDs is their extended optical performance compared with that of bulk graphene. Considerable effort has been devoted to developing the optical applications of GQDs, especially fluorescence-based applications. As novel fluorescent probes, GQDs are highly sensitive to minute perturbations, providing great potential for sensing applications. Meanwhile, the ultrasmall size, high photostability, low toxicity, good biocompatibility and excellent dispersion of GQDs result in improved detection sensitivity, stability, selectivity and security compared with traditional organic dyes and semiconductor quantum dots. To date, the detected analytes include inorganic ions,20,26,36,37,56,60,77,86–93 small organic molecules86,94–100 and large biomaterials101–106 based on either fluorescence turn-on or turn-off mechanisms. In this review, we focus on recent fluorescence sensing applications of GQDs.
3.1 Detection of inorganic ions
GQDs have been widely used as fluorescence sensing probes to detect inorganic ions including metal cations20,26,36,37,56,60,77,86–92,95,107–111 and non-metallic anions.93,112,113
3.1.1 Detection of metal cations using GQDs. Although metal cations play important roles in environmental, biological and chemical systems, they can accumulate in the human body through the food chain, leading to serious damage of the kidneys, liver and brain. Therefore, highly sensitive and selective sensors for metal cations are urgently required. GQDs display strong fluorescence and possess rich organic groups on their surfaces, making them suitable for fluorescence sensing probes for metal ion detection. To date, various metal cations including Fe3+,26,36,37,56,86,87 Hg2+,77,88–91 Cu2+,92,107 Cr6+,95 Cd2+,108 Pb2+,109,110 Ag+,20 Au3+,60 and Ni2+,111 have been detected using different GQD-based fluorescent sensors. Most studies chiefly centre on the detection of Fe3+, Hg2+ and Cu2+, probably because of their prominent role or high toxicity in biological systems.Zhou et al. used pure GQDs exhibiting green fluorescence as a fluorescent probe for sensitive detection of Fe3+, achieving a lower detection limit of 5 × 10−9 M compared with those of reported Fe3+ probes, which include fluorescent nanographene, rhodamine 6G derivatives and 8-quinolinol (oxine) and quinazolinone derivatives.86 The GQDs also exhibited relatively high selectivity for Fe3+ with little interference from Cu2+, Fe2+ and Hg2+, which is caused by the specific coordination interaction between Fe3+ and the phenolic hydroxyl groups of GQDs. Our group developed a controllable top-down method to prepare novel GQDs displaying yellow fluorescence using mesoporous silica as a nanoreactor.56 The resulting GQDs with abundant oxygen-containing groups such as phenolic hydroxyl and carboxyl groups were used for highly selective determination of Fe3+ in tap water with satisfying recovery based on the fluorescence turn-off mechanism. The surface states of GQDs were modified with NaOH to investigate the quenching mechanism and high selectivity for Fe3+ of the GQDs. The NaOH-treated GQDs exhibited more noticeable quenching signals towards Cu2+, Co2+, Mn2+ and Ni2+ than other metal ions in neutral solution; in particular, a depressed response towards Fe3+ was observed. These results demonstrated that the high selectivity of the original GQDs for Fe3+ predominantly relied on the coordination between the phenolic hydroxyl groups of the GQDs and Fe3+.
Heteroatom doping can drastically alter the electronic characteristics of GQDs, thus leading to unusual fluorescent properties and novel applications. Li et al. electrochemically synthesised a S-GQD fluorescent probe with blue-green fluorescence that showed a more sensitive fluorescence response to Fe3+ than pure GQDs.36 This is because S doping tuned the electronic local density of GQDs, and thus promoted the coordination interaction between Fe3+ and phenolic hydroxyl groups on the surfaces of S-GQDs. This specific coordination interaction caused fluorescence quenching of the S-GQDs. The S-GQDs exhibited high selectivity towards Fe3+ with a low detection limit of 4.2 nM and linear range of 0–0.70 μM. Importantly, this novel fluorescent probe was successfully used for direct analysis of Fe3+ in human serum, indicating potential applications in clinical diagnosis. Fig. 5 illustrates the quenching mechanism of the S-GQDs and sensing performance of this Fe3+ sensor.
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| Fig. 5 (a) Fluorescence quenching mechanism of S-GQDs in the presence of Fe3+. (b) Electron transfer process from S-GQDs to Fe3+. (c) Fluorescence spectra of S-GQDs (5 μg mL−1) in the presence of different concentrations of Fe3+. The inset in (c) shows photographs of S-GQD aqueous solutions containing different concentrations of Fe3+ under UV irradiation (365 nm). (d) Fluorescence quenching values ΔF plotted against Fe3+ concentration. The inset in (d) is the linear calibration plot for Fe3+ detection. (Reprinted with permission from ref. 36. Copyright 2014 American Chemical Society.) | |
Surface-functionalised GQDs have recently been used for the fluorescent determination of Fe3+. Ananthanarayanan et al. prepared GQDs functionalised with the IL BMIMPF6 that displayed blue fluorescence using an electrochemical cleavage method with the aid of BMIMPF6. The IL-functionalised GQDs were used for the optical detection of Fe3+ based on the quenching mechanism.37 The imidazole ring of BMIM+ both improved the dispersion of GQDs and endowed them with strong binding affinity for Fe3+. The constructed sensor exhibited good selectivity towards Fe3+ compared with Mg2+, Fe2+, Zn2+, Co2+, Ni2+, Cd2+ and K+, with a theoretical lower detection limit of ∼7.22 μM. More recently, Guo and co-workers used rhodamine B derivative (RBD)-functionalised GQDs (denoted RBD-GQDs) as an effective fluorescent probe for the sensitive detection of Fe3+ based on a rare fluorescent turn-on mechanism.87 The RBD-GQD probe displayed a detection limit as low as 0.02 μM in cancer stem cells. They found that the water solubility, sensitivity, photostability and biocompatibility of RBD were drastically improved when RBD was covalently linked to GQDs. The RBD-GQD-based fluorescent sensor also exhibited high selectivity for Fe3+ in comparison with Ca2+, Cd2+, Co2+, Cu2+, Hg2+, K+, Mg2+, Mn2+, Na+, NH4+, Ni2+, Pb2+, Zn2+ and Fe2+, with slight interference of Al3+.
Similar to the detection of Fe3+, pure GQDs,88,89 heteroatom-doped GQDs77 and surface-functionalized GQDs90,91 have been used to detect hazardous Hg2+. For example, Chakraborti et al. directly used pure GQDs as a fluorescent probe to develop a novel sensing platform for Hg2+ in aqueous solution based on the turn-off mechanism.88 High selectivity for Hg2+ was demonstrated by comparing the quenched fluorescence intensity of the GQD solution in the presence of only Hg2+ with that in the presence of other metal ions (Li+, Na+, K+, Ca2+, Mg2+, Mn2+, Fe3+, Cu2+, Zn2+, Al3+, Co2+, Ag+, Cr3+, Ni2+, Cd2+ and Pb2+) at the same concentration. The quenching mechanism was investigated using steady-state and time-resolved spectroscopy. The authors reported that the adsorption of Hg2+ onto the surface of the GQDs caused the electronic structure of the probe to change, which ultimately resulted in fluorescence quenching. The calculated detection limit for Hg2+ of this sensor was about 3.36 μM. Shi and colleagues used oxygen-rich nitrogen-doped GQDs (N-OGQDs) to develop an efficient fluorescent probe for the sensitive detection of Hg2+ in river water.77 The fluorescence quenching mechanism of the N-OGQDs was attributed to non-radiative electron transfer from the excited states of the N-OGQDs to the d orbital of Hg2+. This fluorescent sensor showed high sensitivity for Hg2+ with a low detection limit of 8.6 nM. It is worth noting that Pb2+, Cd2+, Cu2+, Ni2+ and Fe3+ all interfered with the detection of Hg2+ to a certain extent, so triethanolamine and sodium hexametaphosphate were added as chelating agents for Pb2+, Cd2+, Cu2+, Ni2+ and Fe3+. Recently, Tan's group achieved highly selective fluorescence detection of Hg2+ in HeLa cells based on the fluorescence quenching mechanism using a thymine-rich DNA-modified GQD (DNA-GQD) fluorescent probe.90 The developed Hg2+ sensor not only had an ultralow detection limit of 0.25 nM and relatively wide linear range of 1 nM to 10 μM, but also showed higher selectivity for Hg2+ than other metal ions, including Na+, K+, Li+, Ag+, Pb2+, Mg2+, Ni2+, Zn2+, Co2+, Cd2+, Cu2+, Mn2+, Ca2+ and Fe3+, at the same concentration. The excellent selectivity of the DNA-GQDs for Hg2+ was ascribed to the strong coordination of the spatially separated thymine bases with Hg2+. More importantly, they found that the unmodified GQDs displayed only a small fluorescence response towards Hg2+ compared with the DNA-GQD probe. This suggested that the fluorescent quenching mechanism involved the nonradiative electron transfer quenching of DNA-GQDs by Hg2+ binding to the thymine bases of DNA to form a T–T mismatch hairpin structure.
To detect Cu2+, Wang et al. utilised GQDs displaying blue fluorescence as a fluorescent probe.92 They achieved the successful detection of Cu2+ in water based on the quenching of GQD fluorescence by Cu2+. The sensor was very sensitive to Cu2+ compared with its sensitivity to other metal ions, including Fe3+, Al3+, Mn2+, Zn2+, Ca2+, Mg2+, Ag+, Ni2+, Co2+, Pb2+, Cd2+, Hg2+, Li+, Na+ and K+, and showed high selectivity. Furthermore, it also exhibited a linear range of 0–15 μM with a low detection limit of 0.226 μM. The authors also investigated the fluorescence quenching mechanism of this probe. They deemed that the quenching largely resulted from the formation of non-fluorescent complexes between Cu2+ and the oxygen-containing groups of the GQDs as electron donors. Qu's group reported an amino-functionalised GQD (afGQD) probe to sense Cu2+ based on the fluorescence turn-off mechanism.107 They found that the afGQDs displayed a larger fluorescence response towards Cu2+ than towards Al3+, Ag+, Co2+, Cd2+, Ni2+, Mg2+, Mn2+, Pb2+, Zn2+, Fe2+, Fe3+ and Hg2+. In contrast, pure GQDs had no selectivity for Cu2+ with non-negligible interference of Al3+, Co2+, Cd2+, Mn2+, Pb2+, Fe2+ and Fe3+. A possible reason for this may be that the introduction of amino groups increased the binding affinity of the afGQDS with N and O coexisting on their surface for Cu2+, increasing the chelation kinetics of Cu2+ compared with that of other metal ions. The constructed sensor showed a linear range of 0–100 nM with a detection limit of 6.9 nM and demonstrated fluorescence sensing of Cu2+ in living cells.
For the detection of Pb2+, Qian et al. developed a highly selective and sensitive fluorescent Pb2+ sensor based on aptamer-functionalized GQDs.109 In their study, the aptamer-functionalized GQDs fluorescent probe were firstly fabricated and then assembled on the surface of graphene oxide (GO) through electrostatic attraction and π–π stacking, resulting in a sequent fluorescence quenching due to a photoinduced electron transfer between GQDs and GO. The quantification of Pb2+ was achieved in the above aptamer/GQD/GO system through the liberation of aptamer–GQDs from GO triggered by the addition of Pb2+, leading to a recovery of fluorescence.
3.1.2 Detection of non-metallic anions based on GQDs. Recently, GQDs have also been used as fluorescent probes to detect non-metallic ions including sulphite,113 sulphide,93 and pyrophosphate (PPi) ions112 via “on–off–on” fluorescence responses.Similar to carbon quantum dots for highly selective detection of PPi,114 Lin et al. prepared N-GQDs with greenish-yellow fluorescence by hydrothermal treatment of lysine and GO (Fig. 6).112 An Eu3+-modulated N-GQD off–on fluorescent probe for PPi detection was constructed based on the following considerations: (a) Eu3+ can quench the fluorescence of N-GQDs by coordination of Eu3+ to the carboxyl and amido groups on the N-GQD surface; (b) PPi can recover the quenched fluorescence signal of N-GQDs by removing the Eu3+ because PPi possesses a higher affinity for Eu3+ than the carboxy groups of the N-GQDs. Other anions like F−, Cl−, Br−, I−, HCO3−, CO32−, Ac−, NO2−, S2− and PO43− did not recover the fluorescent signal, showing the good potential of this system for selective detection of PPi. The developed PPi sensor exhibited a linear range over 0.3–5 μM with a detection limit of 0.074 μM and successfully detected PPi in urine samples.
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| Fig. 6 Schematic illustrations of (a) the preparation of N-GQDs and (b) the detection of PPi with Eu3+-modified N-GQDs. (Reprinted with permission from ref. 112. Copyright 2015 Royal Society of Chemistry.) | |
3.2 Detection of small organic molecules using GQDs
Similar to carbon quantum dots for sensitive detection of organic molecules,78,80 monitoring small organic molecules with fluorescent GQDs has also become an interesting objective in recent years. Organic materials such as H2O2,86 ascorbic acid,94 bisphenol A,96 dihydroxybenzene,97 hydroquinone,98 2,4,6-trinitrotoluene,99 urea,100 melamine,115 glucose116 and 2,4,6-trinitrophenol (TNP)76 have been optically detected using fluorescent GQD probes based on a turn-on or turn-off fluorescence response.
Inspired by their successful detection of metal ions, researchers have recently used GQDs as direct or indirect sensing probes to detect small organic molecules. As a direct sensing probe, the fluorescence of GQDs can be directly quenched or enhanced by specific organic molecules.76,116 For example, Lin et al. prepared N-GQDs displaying strong blue fluorescence that was directly quenched by TNP.76 Based on this discovery, the authors directly used N-GQDs as a probe to construct a TNP sensor that showed a linear range of 1–60 μM with a detection limit of 0.30 μM. The selectivity of the constructed TNP sensor was also investigated using structurally related aromatic materials (methylbenzene, phenol and nitrobenzene, 4-nitrotoluene, 2,4-dinitrotoluene, 2,4-dinitrophenol and 2,4,6-trinitrotoluene) and metal ions (Ca2+, Co2+, Ag+, Pb2+, Mn2+, Cd2+, Ba2+, K+, Na+, Al3+, Zn2+, Cu2+, Cr3+, Ni2+, Fe3+ and Hg2+) as interfering substances. The sensor displayed high selectivity towards TNP, with only small fluorescence responses towards Fe2+, Fe3+ and Hg2+, which were effectively eliminated by adding ethylenediaminetetraacetic acid. The researchers speculated that the fluorescence quenching of N-GQDs by TNP was caused by electron transfer and the formation of a non-fluorescent complex via the strong electrostatic interactions between N-GQDs and TNP.
Zhang and co-workers prepared B-GQDs with boronic acid groups on their surfaces.116 Interestingly, the fluorescence intensity of the B-GQDs increased linearly with glucose concentration in the range of 0.1–10 mM with a detection limit of 0.03 mM. As illustrated in Fig. 7, they postulated that the two cis-diol units in glucose can react with two boronic acid groups on the B-GQD surface to form structurally rigid B-GQD-glucose aggregates, restricting intramolecular rotation and thus resulting in enhanced fluorescence. The B-GQD sensor showed good selectivity for glucose compared with fructose, galactose and mannose. This is because fructose, galactose and mannose do not contain cis-diol units to enhance the fluorescence of B-GQDs by cross-linking-induced aggregation.
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| Fig. 7 (a) Schematic representation of boron-doped graphene quantum dots (BGQDs). (b) Proposed aggregation-induced photoluminescence (PL) mechanism of glucose sensing by BGQDs. (Reprinted with permission from ref. 116. Copyright 2014 American Chemical Society.) | |
The fluorescence of GQDs can be quenched directly by the detected organic molecules with the aid of metal ions or oxidation agents.115 For instance, Zhu's group developed a rapid fluorescence sensing platform for melamine by direct fluorescence quenching of GQDs with predominantly aromatic sp2 domains in the presence of Hg2+.115 They speculated that after adding melamine into the GQD solution containing Hg2+, melamine first coordinated with Hg2+ through its nitrogen atoms (amine and triazine groups) and then Hg2+ interacted with the surface of GQDs through π–π stacking between the GQDs and melamine, thus leading to fluorescence quenching of the GQDs. The constructed melamine sensor exhibited a linear range of 0.15–20 μM with a detection limit of 0.12 μM and was successfully used for melamine detection in raw milk with satisfactory recovery. He and co-workers found that hydroquinone was oxidised to p-benzoquinone in the presence of dissolved oxygen with effective fluorescence quenching of GQDs.98 In their experiment, the GQDs served as a peroxidase-mimicking catalyst to oxidise hydroquinone to p-benzoquinone. The newly produced p-benzoquinone quenched the fluorescence of the GQD probe. The developed hydroquinone sensor had a good linear relationship in the range of 0.01–30 μM with a low detection of 5 nM. This novel sensor was successfully applied to hydroquinone detection in tap water, lake water and rain water samples. It should be pointed out catechol, dopamine and rutinum significantly interfered with hydroquinone detection.
As an indirect sensing probe, the fluorescence of GQDs can first be quenched by metal ions and then recovered by specific organic molecules.94,95 For example, Liu et al. developed a simple GQD-based fluorescence sensing system for rapid detection of ascorbic acid in the presence of Cu2+.94 Their system was based on the fluorescence quenching of GQDs by Cu2+ via efficient electron transfer between the GQDs and Cu2+. The addition of ascorbic acid allowed the fluorescence of the GQDs to be recovered by destroying the interaction between Cu2+ and the GQDs because ascorbic acid, as a strong reducing agent, could reduce Cu2+ to Cu+. The constructed sensor showed high selectivity for ascorbic acid compared with urine acid, citric acid, oxalic acid, dopamine, mannose, fructose, glucose, Na+, K+, Ca2+, Mg2+, Fe3+, Cl− and NO3−. Its linear range and detection limit were 0.3–10 μM and 94 nM, respectively. The sensor detected ascorbic acid in vitamin C samples with satisfactory results.
3.3 Detection of biomaterials using GQDs
The versatility of GQD-based fluorescent sensors is also evidenced by their ability to detect a range of biotargets including alkaline phosphatase,101 DNA,102–104 thrombin,105 protein kinase106 the mecA gene sequence,117 microRNAs,118 trypsin,119 phosphate-containing metabolites,120 heparin and chondroitin sulfate,121 acetylcholinesterase,122 cardiac marker antigen Troponin I (cTnI)123 and human immunoglobulin G.124 The most commonly used methods to detect biomaterials are based on specific fluorescence resonance energy transfer (FRET) between functional GQDs and a quencher. For example, Qian et al. developed an efficient fluorescence sensing platform for the selective and sensitive detection of DNA using GO as a quencher.103 As shown in Fig. 8a, they prepared fluorescent single-stranded DNA-functionalised GQDs (ssDNA-rGQDs) through a condensation reaction between connecting DNA (cDNA) and GQDs reduced by NaBH4. Fluorescence quenching of the ssDNA-rGQD probe occurred after the addition of GO quencher because of the adsorption of the ssDNA-rGQD probe on the GO surface through electrostatic attraction and π–π stacking interactions. The fluorescence of the probe was recovered by introducing target DNA (tDNA) into the testing solution containing ssDNA-rGQD and GO because the detachment of the dsDNA-rGQDs from GO, which were resulted from the hybridization between the ssDNA-rGQDs and tDNA. When tDNA was replaced with DNA with a single base mismatch, the recovered fluorescence intensity was much lower than that achieved using tDNA, indicating the high selectivity of the sensor for tDNA. The developed DNA sensor exhibited a wide linear range of 6.7–46.0 nM with a low detection limit of 75.0 pM.
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| Fig. 8 (a) Schematic illustration of a universal fluorescence sensing platform for the detection of DNA based on fluorescence resonance energy transfer (FRET) between graphene quantum dots (GQDs) and graphene oxide. (Reprinted with permission from ref. 103. Copyright 2014 Royal Society of Chemistry.) (b) Schematic illustration of a fluorescent biosensor for trypsin based on self-assembled GQDs. (Reprinted with permission from ref. 119. Copyright 2013 Royal Society of Chemistry.) | |
More recently, Bhatnagar and co-workers used graphene as a quenching agent to construct a novel GQD-based fluorescent sensor to detect cardiac marker antigen cTnI in blood based on FRET.123 The detection of cTnl was accomplished by the following three steps: afGQDs were covalently conjugated with the antibody anti-cardiac Troponin I (anti-cTnI) to form a fluorescent anti-cTnl/afGQD nanoprobe. The anti-cTnl/afGQD probe was absorbed onto the surface of a graphene quencher through π–π stacking interactions, resulting in fluorescence quenching because of FRET between them. Finally, quantification of the target antigen cTnI was achieved by adding cTnI to the anti-cTnI/afGQD/graphene system to liberate anti-cTnI/afGQDs from graphene, leading to fluorescence recovery. Because of the strong interaction of cTnI with anti-cTnI, the constructed sensor showed high selectivity for cTnI compared with non-specific antigens. Detection of cTnI was realised over a wide range from 0.001 to 1000 ng mL−1 with a limit detection of 0.192 pg mL−1.
Besides graphene and GO, gold nanoparticles117 and CNTs102 have also been used as quenchers to detect biomaterials based on FRET. However, it should be noted that these GQDs required functionalization to prepare the sensors. Therefore, some novel label-free GQD-based fluorescent sensors for the detection of biomaterials have been developed. For example, Li et al. prepared a novel trypsin sensor based on the cytochrome c (Cyt c)-induced self-assembly of GQDs.119 Fig. 8b outlines the detection mechanism of the sensor. The fluorescence of the GQDs was first quenched by introducing an electron transfer protein (Cyt c) into the GQDs. The GQDs aggregated in the presence of Cyt c because of the electrostatic interaction between Cyt c and GQDs as well as the specific coordination interaction between Fe3+ in Cyt c and the phenolic hydroxyl groups of GQDs. The fluorescence of GQDs was then recovered by adding the target trypsin to the Cyt c/GQD system because the Cyt c quencher is cleaved by trypsin into smaller fragments (arginine and lysine residues) along with the reduction of Fe3+ and GQDs, leading to the restoration of fluorescence. The change of fluorescent intensity reflected the amount of trypsin added, providing a trypsin sensor with a low detection limit of 33 ng mL−1 and high selectivity for trypsin compared with bovine serum albumin, lysozyme, papain and pepsin. A similar GQD-based fluorescent sensor for heparin and chondroitin sulfate detection was also achieved by replacing Cyt c with dendrimer nanoparticles with multiple positive charges.121 Furthermore, with promising applications of CQDs in the detection of various enzymes such as acid phosphatase,125 alkaline phosphatase,126,127 tyrosinase,128 acetycholinesterase,129 hyaluronidase,130 human fetoprotein etc.,131 the detection of enzyme based on cousin GQDs may be expected in the future.
3.4 Fluorescence sensing mechanism
As previously mentioned, GQDs have been well applied as fluorescent probes for selective and sensitive detections of inorganic ions, small organic molecules and large biomaterials. Although there are various targets, the constructed fluorescence sensing platform was chiefly based on turn-off (fluorescence quenching) and turn-on (fluorescence recovering) fluorescence responses.92,94,103,107,120 As for the turn-off response, the fluorescence quenching of GQDs or functionalized GQDs by targets appears to be static quenching (complexation),92 dynamic quenching (collisional deactivation)120 or sometimes involving both static and dynamic quenching mechanisms,107 which usually can be analyzed based on the evaluation of fluorescence lifetime. For a turn-on fluorescence response, the mechanism for GQDs-based sensor is usually considered to contain two steps.94,103 Firstly, the fluorescence quenching of GQDs or functionalized GQD occurs because of the strong interaction between GQDs (or functionalized GQD) and quencher. Secondly, the pre-formed composite structure of GQDs and quencher is destroyed with the addition of targets, leading to the liberation of fluorescent GQDs into solution and the corresponding fluorescence recovery. However, the understanding on the fluorescence recovering process is still vague when GQD, quencher and target are in coexistence.
4. Conclusion and outlook
In this review, we have summarised recent progress in fluorescent GQD research, focusing on their synthesis and fluorescence sensing applications for the detection of inorganic ions, small organic molecules and large biomaterials. Various approaches to prepare GQDs and construct fluorescent sensing platforms have been discussed in detail. Regarding the preparation of GQDs, both top-down and bottom-up methods have been developed that use hydrothermal/solvothermal, microwave, ultrasound, CVD and electrochemistry. Although numerous top-down and bottom-up methods have been developed, the exploration of the synthesis of high-quality GQDs with uniform lateral size and controllable layer number and surface composition is still ongoing. Nanoreactor-confined synthesis of GQDs based on either a top-down or bottom-up strategy provides GQDs with uniform lateral size and controllable layer number. Inspired by this, we expect that by using an appropriate nanoreactor and precursor, GQDs with a uniform structure may be obtained in the future. In particular, bottom-up methods rather than top-down approaches that involve nonselective cutting processes are anticipated to provide GQDs with desired structures. The unique planar structure, high surface area, tunable surface composition, high photostability, good biocompatibility and low toxicity of GQDs make them suitable for constructing a wide range of fluorescence sensing platforms for the sensitive detection of various targets based on turn-on and turn-off fluorescence responses. GQD-based fluorescent sensors show promise in detection of inorganic ions, small organic molecules and large biomaterials. The main issues facing GQD-based sensors are selectivity improvement and clear understanding of their fluorescence response mechanisms. Furthermore, GQDs with red-emitting fluorescence and high light efficiencies are hoped to be developed to produce GQDs for target detection, especially in biological system in future work. We hope this review stimulates continued interest and endeavour in the area of photoluminescent GQDs.
Acknowledgements
The authors acknowledge financial support from the ‘1000 Talent Program’ (The Recruitment Program of Global Experts), the National Natural Science Foundation of China (21473247), the ‘Young Creative Sci-Tech Talents Cultivation Project’ (2013711012, 2013711016) and the ‘International Science and Technology Cooperation Project’ (20146003) of the Xinjiang Uyghur Autonomous Region.
Notes and references
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