Applications of graphene in quality assurance and safety of food

Trends in Analytical Chemistry 60 (2014) 36–53

Contents lists available at ScienceDirect

Trends in Analytical Chemistry j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / t r a c

Applications of graphene in quality assurance and safety of food Ashok Kumar Sundramoorthy, Sundaram Gunasekaran * Department of Biological Systems Engineering, University of Wisconsin-Madison, 460 Henry Mall, Madison, WI 53706, USA

A R T I C L E

I N F O

Keywords: Adsorbent Biosensor Chemical contaminant Electroanalysis Food composition Graphene Graphene oxide Packaging material Pesticide Toxin

A B S T R A C T

There is tremendous interest in graphene and its derivatives [graphene oxide (GO) and reduced GO (rGO)] due to their superior mechanical, thermal, electrical, optical, and chemical-adsorption properties. In the past few years, graphene-based materials attracted much attention and were used for a myriad of practical applications in various industries. In this review, we present a comprehensive, state-of-the art assessment of graphene applications in the food industry. We critically examine recent developments on graphene synthesis from foodstuffs, use of graphene for food analyses, and graphene-based analytical methods in detection (e.g., composition, contaminants, toxins, and volatile organic compounds), which help to ascertain quality and/or safety of foods. We also discuss antibacterial properties of graphenebased nanomaterials and their applications in food packaging. © 2014 Elsevier B.V. All rights reserved.

Contents 1. 2. 3.

4.

5.

Introduction ........................................................................................................................................................................................................................................................... Graphene synthesis from foodstuffs ............................................................................................................................................................................................................. Graphene in detecting food quality .............................................................................................................................................................................................................. Detection of chemical contaminants .............................................................................................................................................................................................. 3.1. Detection of food composition ......................................................................................................................................................................................................... 3.2. Graphene-based ion-selective electrodes .................................................................................................................................................................... 3.2.1. Detecting volatile organic compounds ........................................................................................................................................................................................... 3.3. Food safety ............................................................................................................................................................................................................................................................. Extraction and detection of toxins ................................................................................................................................................................................................... 4.1. Detection of pesticides ........................................................................................................................................................................................................................ 4.2. Antibacterial properties of graphene .............................................................................................................................................................................................. 4.3. Summary ................................................................................................................................................................................................................................................................ Outlook and challenges ....................................................................................................................................................................................................................... 5.1. References ..............................................................................................................................................................................................................................................................

1. Introduction The food industry is one of the largest, worth several trillions of dollars worldwide. The heart and soul of this complex, global enterprise is ensuring high quality and safety of the foods that we consume. While the food industry typically lags other industries, such as electronics and automobiles, in adopting new technologies, nanomaterial-based applications have found their way into the food industry. There are several examples where nanotechnology

* Corresponding author. Tel.: (608) 262-1019; Fax: (608) 262-1228. E-mail address: [email protected] (S. Gunasekaran). http://dx.doi.org/10.1016/j.trac.2014.04.015 0165-9936/© 2014 Elsevier B.V. All rights reserved.

36 37 37 37 41 44 45 46 46 46 48 48 50 50

has helped to improve taste, texture, shelf life, nutrient delivery, and the overall quality and safety of foods [1,2]. For example, titanium dioxide (TiO2) and silver (Ag) nanoparticles (NPs) have been used as antimicrobial agents in storage containers for foods and beverages. According to the US Food and Drug Administration (FDA), direct addition of Ag salts up to 17 μg/kg is allowed as disinfectant in bottled water [3]. However, increased use of engineered nanomaterials in the food industry has also raised concerns regarding their potential toxicity and impact on human health. For example, TiO2-NPs extracted from chewing gum were investigated for their toxicity [4]. Though they were considered safe, a few studies suggest that TiO2-NPs could pass through the gastrointestinal tract and slowly distribute and

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information. Graphene is as a new sorbent in extraction (e.g., cocaine, adenosine, sulfonamide antibiotics, carbamate pesticides, pyrethroid pesticides, phenols, methyl parathion, squalene, and chlorophenols) from environmental, biological and food samples [24]. Graphene-based sorbents are superior to other sorbents, including C18, silica, graphitic carbon, single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs) in terms of sorption capacity, ease of elution, cost of material, and recovery of extracted analytes. 2. Graphene synthesis from foodstuffs

Fig. 1. Graphene applications span various fields of science, engineering, and technology.

accumulate in other organs [5]. Efforts to investigate further our understanding of the cytotoxicity of engineered NPs used in foodstuffs are ongoing [6]. Biosensors incorporating nanomaterials have the potential to improve the speed, the sensitivity and the analytical accuracy needed to detect the presence of molecular contaminants or adulterants in complex food matrices [7]. Gold NPs (AuNPs) are popularly employed in biosensors, since the aggregation of AuNPs leads to visibly perceptible color change, signaling the presence of the analyte being tested. The use of AuNPs [8,9], Au nanorods [10,11], and carbon nanotubes (CNTs) [12] particularly helped to detect the presence of gases, aromas, chemical contaminants and pathogens, or respond to changes in environmental conditions. Graphene is one atom thick, two-dimensional (2-D) nanosheet of graphite discovered by Novoselov et al [13]. It possesses high electron mobility (250,000 cm2/V s), exceptional thermal conductivity (5000 W m−1 K−1), superior mechanical properties (e.g., Young’s modulus of 1 TPa), large specific surface area (>100 m2 g−1), good electron transfer ability and good biocompatibility [14]. High-quality graphene (i.e., without structural defects) can be synthesized by chemical-vapor deposition (CVD) [15]. Furthermore, graphene oxide (GO) or reduced GO (rGO) can be derived from graphite by chemical oxidation [16] or electrochemical exfoliation [17]. In the past few years, there were numerous exciting applications of graphene in various fields of science, engineering, and technology [18,19]. For example, as illustrated in Fig. 1, graphene is used in transparent conductors, flexible electronics, field-effect transistors, fuel cells, batteries, solar cells, biomaterials, biosensors, and water purifiers [19,20]. Also, graphene-based applications are on the rise, with innovative developments that help ensure food quality and safety [21,22]. To improve agricultural productivity, pesticides, herbicides, insecticides and fungicides are commonly used, and are potentially toxic if allowed to remain in the food chain in high enough concentrations [23], so quality and safety of foods must be evaluated before delivery to the consumer market. In processed foods, preservatives, colorants and other additives are used to enhance consumer appeal and/or shelf life. Some of these agents are deleterious, so their presence needs to be evaluated. Thus, new analytical methods and technologies are needed to generate rapid, reliable, and precise

CVD is used to synthesize thin films of various nanomaterials using thermochemical vapor-phase reactions in a vacuum furnace to achieve deposition of the desired material on a substrate at high temperature (~1000°C) [25]. Graphene can also be synthesized on a metal-film substrate via CVD by flowing hydrogen and methane gases (carbon source) with a metal catalyst; the methane decomposes, leaving carbon atoms deposited on the substrate to form graphene layers. Ruan et al. used food materials (e.g., cookies, and chocolate) as the carbon source to synthesize monolayer graphene [26]. They obtained a high-quality graphene film on a Cu foil at 1050°C under H2/Ar flow (Fig. 2A). These films did not exhibit significant disorder (D) bands in their Raman spectra (Fig. 2B,C), signifying the presence of few defects. Also, the large 2 D/G ratio suggested that the graphene synthesized was a monolayer film. Calcinations of glucose with dicyandiamide produced freestanding monolayers to oligolayered graphene, and layered graphic carbon nitride (g-C3N4) acted as a sacrificial template, which underwent complete thermolysis at 750°C. In the subsequent step, graphene-like sheets were liberated at high temperatures (Fig. 2D). However, graphene obtained from this method contains nitrogen atoms in the graphene lattice, mainly in the form of “pyridinic” nitrogen and a minor amount of “graphitic” nitrogen [27]. Qu et al. synthesized graphene from alfalfa plants by treating alfalfa shoots with nitric acid at 70°C for 300 min and obtained a black graphene precipitate. It is interesting to note that CNTs were produced in the initial stages from plant-cell walls, and were later converted to graphene by unrolling the nanotubes with treatment by nitric acid [28]. Gupta et al. produced a graphene-coated composite to remove organics in contaminated water by heating a mixture of river sand and sugar in a furnace at 750°C under an N2 atmosphere [29]. Kalita et al. used solid camphor as the precursor material in a microwave surface-wave plasma CVD process [30], in which graphene layers were deposited on a Cu foil at a relatively low temperature (<600°C). Moreover, synthesized graphene film could be easily transferred to a transparent plastic substrate by wet etching, and had a sheet resistance of 8.23 kΩ/square. 3. Graphene in detecting food quality 3.1. Detection of chemical contaminants Surface-enhanced Raman spectroscopy (SERS) is an analytical technique used to study and to identify biomolecules or chemicals by their enhanced (of the order of 104–1014) bands in the Raman spectra [31]. The intensity of Raman peaks of the molecules could be enhanced on the substrate (metal NPs) due to electromagnetic or chemical mechanisms [32]. Graphene is a good substrate to investigate the chemical enhancement of SERS [33]. Liu et al [34]. prepared a graphene nanomesh with controlled size and density of holes, by first depositing a Cu film on graphene and then removing the Cu film by annealing to leave plenty of hole rims around the CuNPs. They used this graphene nanomesh to detect rhodamine B (RhB) by SERS. The intensity of the Raman bands on

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A.K. Sundramoorthy, S. Gunasekaran/Trends in Analytical Chemistry 60 (2014) 36–53

Fig. 2. (A) Experimental apparatus for the growth of graphene from food in a tube furnace. (Left) Cu foil with the carbon source contained in a quartz boat is placed in the hot zone of a tube furnace. (Right) Cross-sectional view that represents the formation of pristine graphene on Cu substrate. (B,C) The Raman spectra of graphene derived from Girl Scout cookie and chocolate. {Adapted with permission from [26]}. (D) A protocol for free-standing graphene synthesis. (Bottom) Repetition motifs of an ideal g-C3N4 plane (middle) and graphene (right); C: black or gray, N: blue. {Adapted with permission from [27]}.

single-layer graphene nanomesh (SGNM) (with different Cu films) was significantly greater than those on single-layer graphene (SLG) (Fig. 3A). They attributed this result to the ability of edges in the SGNM to enhance Raman bands by increasing the local charge transfer and to absorb RhB molecules. Xie et al [36]. developed a SERS sensor for detecting prohibited colorants (e.g., amaranth, erythrosine, lemon yellow, and sunset yellow) in foodstuffs using graphene/AgNPs as substrates. The characteristic Raman peaks were significantly more enhanced on the graphene/Ag substrate than on the Ag substrate alone, due to the excellent adsorbent effect of graphene and AgNPs. The limits of detection (LODs) of this graphene-based SERS were 10−5 M for amaranth, lemon yellow, sunset yellow and 10−7 M for erythrosine. The aqueous dispersion prepared of the homogeneous gum arabic (GA)stabilized graphene [1.7–2.1-nm thick (i.e., fewer than four layers)]

was stable for more than a month in a sealed bottle. GA could also reduce Ag+ ions and immobilize them on graphene sheets for fabricating AgNPs/GA-graphene hybrid (Fig. 3B) [35]. Concentrated electromagnetic fields are the reason for SERS, when there are two or more coupled NPs or nanostructured surfaces with closely spaced features [37]. The SERS activity of the AgNP/GAgraphene hybrid was investigated using aminothiophenol (4-ATP) as a Raman-probe molecule. There was no evidence that the Raman peak of 4-ATP was detected on the surface of the GA-graphene hybrid. However, the SERS spectrum of 4-ATP on the Ag/GAgraphene hybrid exhibited four b2 modes at 1145 cm−1, 1392 cm−1, 1445 cm−1 and 1572 cm−1 and one a1 mode at 1072 cm−1. This indicated that the Ag/GA-graphene hybrid film was suitable for SERS detection of 4-ATP [35] (Fig. 3C). Compared with the spectrum of the solid 4-ATP, there are distinct frequency shifts due to the changes

A.K. Sundramoorthy, S. Gunasekaran/Trends in Analytical Chemistry 60 (2014) 36–53

Fig. 3. (A) Raman spectra of 0.5-nm thick RhB deposited on SLG, SGNM-1, SGNM2, and SGNM-4. The spectra have been offset vertically for clarity. {Adapted with permission from [34]}. (B) Photographs of (a) AgNO3 aqueous solution, (b) GA aqueous solution, (c) AgNO3 and GA mixture after reduction of Ag ions, (d) mixture of AgNO3 and GA-G aqueous dispersion after reduction of Ag ions, and (e) Ag/GA-G hybrid redispersed in water. (C) Raman spectra of solid 4-ATP, SERS spectra of 4-ATP (10−6 M) on (a) GA-G, (b) GA-capped Ag NPs, and (c) Ag/GA-G hybrid. {Adapted with permission from [35]}.

in the band intensity. The deformation vibration of the carbon– sulfur (C–S) bond shift (1092–1074 cm−1), and another frequency shift (1591–1574 cm−1) were observed due to the formation of strong Ag–S bonds between the Ag and –SH groups of 4-ATP [38]. Oxalic acid (OA) is naturally present in plants, fruits, vegetables and nuts, and could form a less soluble complex with general cations (Ca2+) [39]. When present in high levels in the diet, OA leads to irritation of the digestive system, especially of the stomach and the kidneys [40]. Chen et al [41]. used a platinum NP (PtNP)loaded graphene nanosheet (GNsh) (PtNP-GNsh)-modified electrode to detect OA in the range 0.1–50 mM. The PtNP-GNsh film

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exhibited high electrochemical activity with well-defined oxidation peaks of OA and decreased over potential compared to bare or graphene-modified electrodes. Hydrogen peroxide (H2O2) is a by-product of a large number of oxidase enzymes, and also an essential mediator in food, pharmaceutical, clinical, industrial and environmental analyses [42]. A palladium NP/graphene nanosheet (PdNP)/GNsh film-coated glassycarbon electrode (GCE) showed enhanced electrochemical reduction of H2O2 from 0.1 μM to 1000 μM with an LOD of 0.05 μM. In addition, a PdNP/GNsh-based sensor allowed selective detection of H2O2 in the presence of ascorbic acid, glucose and dopamine [43]. Synthetic aromatic azo dyes are considered harmful because they could cause allergies, migraines, eczema, anxiety, diarrhea and even cancer, if consumed excessively [44,45]. Sunset yellow (SY) and tartrazine (TT) are azo colorants that may be present in common foodstuffs [46]. Gan et al. prepared graphene layer-wrapped phosphotungstic acid (PTA) hybrid film, which provides good selectivity and high sensitivity for simultaneous determination of SY and TT, by exhibiting well-defined oxidation peaks in differential pulse voltammetry with a peak potential separation of ~260 mV. The LODs were 0.5 μg L−1 for SY and 30.0 μg L−1 for TT. Moreover, the graphene– PTA/GCE allowed simultaneous determination of both dyes without the interference of glucose, sucrose and glycine, citric acid, Fe3+, Fe2+ and Ca2+; or amaranth, ponceau R, allura red and quinoline yellow [47]. Using a mesoporous TiO2-decorated grapheme-based hybrid film, they were able to detect Sudan I and Orange II (toxic dyes, food colorants) in the range 3.3 nM–0.66 μM with LODs of 0.60 nM (Sudan I) and 2.85–28.54 nM (Orange II), respectively. This sensor was also tested for measuring Sudan I and Orange II in food extracts with reliable measurements [48–50]. High extraction efficiency of GNsh as adsorbent in solid-phase microextraction (SPME) method was demonstrated for UV filters (benzophenone, octyl salicylate, homosalate, 3-(4-methylbenzylidene) camphor and 2-hydroxy-4methoxybenzophenone) (Table 1) [56]. Malachite green is a dye and an antimicrobial agent used in the food industry. It has emerged as a controversial agent in aquaculture and is considered highly toxic. Hou et al. proposed a graphene quantum dot (GQD)–AuNP–modified GCE for enhanced detection of malachite green with an LOD of 1.0 × 10−7 mol L−1 [62]. Graphene sheets suspended in a poly[N-(1-one-butyric acid)benzimidazole] (PBI-BA) polyelectrolyte solution [63] were coated on an Au electrode, and dramatically improved detection performance for H2O2 (from 2.5 μM to 5 mM with a sensitivity of 1056 mA mM−1 cm−2). A nanocomposite made of tin dioxide (SnO2) and graphene [64] showed high catalytic activity and 10-fold enhanced reduction current of mercury(II), suggesting that the SnO 2 /graphene nanocomposite could be employed as a mercury(II) sensor. Graphene sheets with lateral dimensions less than 100 nm are known as GQDs, which have very low toxicity and exhibit high stability, excellent solubility, stable photoluminescence, and good biocompatibility. A fluorescence “off-to-on” mechanism of bright blue fluorescent glutathione (GSH)-functionalized GQDs (GQDs@GSH) for assaying adenosine triphosphate (ATP) was proposed [65]. The timedependent fluorescence quenching of GQDs@GSH in the presence of Fe3+ occurred due to chelation. The fluorescence restoration of GQDs@GSH–Fe3+ in the presence of ATP was also observed. The formation and the release of the ATP–Fe3+ complex from GQDs@GSH was relatively slow and needed almost 15 min to reach equilibrium. Using this interesting strategy, a method was developed for sensitive quantification of ATP in the range 25–250 μM (Fig. 4). Zheng et al. reported that graphene dots (GQDs) possess more efficient peroxidase-like catalytic activity than GO with large sheet size [66]. GQDs catalyzed the oxidation of peroxidase substrate 3,3,5,5-tetramethylbenzidine (TMB) in the presence of H2O2 and produced a blue product, which was used for H2O2 detection by monitoring changes in the absorbance [67] (Fig. 5A). Fig. 5B shows the

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Table 1 Graphene-based extraction and chromatographic analysis of pesticides, toxins, estrogens, UV filters, bisphenol A and polycyclic aromatic hydrocarbons Analyte

Extraction efficiency (%)

Linear range

Detection limit

Sample matrix

Ref.

0.1–7.5 μg/kg in rapeseed, 0.1– 5.4 μg/kg in peanut, 0.1–4.1 μg/ kg in soybean and 0.1–8.3 μg/ kg in sesame seeds 1.0–7.0 ng L–1

Rapeseed, peanut, soybean and sesame seeds

[51]

Tap water, reservoir water and grape juice

[52]

NH2-Graphene – LC–MS/MS analysis

Thidiazuron; Pymetrozine; Diuron

70.5–100.0

0.001–0.5 mg/L

Magnetic graphene nanocomposite(G-Fe3O4) – GC-ECD Graphene nanosheets coated stainless steel fiber – GC-ECD

Procymidone (P), folpet (F), vinclozolin (V) and ditalimfos (D)

79.2–102.4

15–4500 ng L–1 for P, F and V. 3–900 ng L–1 for V

1,1-Dichloro-2,2-bis-(p’chlorophenyl)ethylene (p,p-DDE), 1,1dichloro-2,2-bis-(p’chlorophenyl)ethane (p,p’-DDD), 1,1,1trichloro-2,2-bis(p-chlorophenyl) ethane (p,p-DDT), dieldrin and endrin Carbofuran, carbaryl, pirimicarb, diethofencarb Herbicides [atrazine, prometon, propazine and prometryn] Benzophenone, octyl salicylate, homosalate , 3-(4-methylbenzylidene) camphor, 2-hydroxy-4methoxybenzophenone Aflatoxins (B1, B2, G1, and G2) Estrogens

80.1–101.1

1–500 ng/L p,p-DDE, 7.5– 1500 ng/L Dieldrin, 2–1000 ng/L Endrin, 2–1000 ng/L p,p-DDD, 3–1500 ng/L p,p-DDT

0.19 ng L−1 (p,p-DDE), 0.79 ng L−1(dieldrin), 0.76 ngL−1(endrin), 0.29 ng L−1(p,p-DDD) and 0.93 ng L−1 (p,p-DDT).

River water sample

[53]

83.8–95.4

0.3–2.4–400.0 ng mL−1

0.1–0.8 ng mL−1

[54]

89.0–96.2

0.1–50.0 ng mL−1

0.025 and 0.040 ng mL−1

Water samples (sea, lake and tap water) Water samples (lake, river and reservoir) River water samples

Graphene-coated fiber – HPLCDAD Graphene-coated Fe3O4 magnetic NPs- HPLC-DAD Graphene-based sol–gel coating as sorbent coupled with GC-MS GO as adsorbent-HPLC Fe3O4@TiO2/GO magnetic microspheres-HPLC Graphene as a SPE adsorbentIC Graphene-based SPE coupled with UPLC–MS/MS GO/fused-silica fiber-GC

99–114

1–5000 ng

L−1

0.5 and 6.8 ng L

−1

[55] [56]

85.1–100.8 70.6–94.5

0.5–100 (ng/g) 5–5000 ng mL−1

0.08–0.65 ng/g 4.3–7.5 ng mL−1

Peanuts Milk powder samples

[57] [58]

Bisphenol A

83.3–104.6

5–20,000 ng mL−1

0.8 ng mL−1

Dairy products

[59]

Lincomycin, azithromycin, tilmicosin, erythromycin, roxithromycin Polycyclic aromatic hydrocarbons

81.7–110.5

0.30–500 μg kg−1

0.09–0.72 μg kg−1

Fish Tissues

[60]

0.05–200 μg/L

0.08 μg/L

Yellow river and local waterworks

[61]

84.58–118.2

DAD, Diode-array detection; ECD, Electron-capture detector; GC, Gas chromatography; HPLC, High-performance liquid chromatography; IC, Ion chromatography; LC, Liquid chromatography; MS, Mass spectrometry; MS/MS, Tandem mass spectrometry; UPLC, Ultra high-performance liquid chromatography.

A.K. Sundramoorthy, S. Gunasekaran/Trends in Analytical Chemistry 60 (2014) 36–53

Substrate and separation technique

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determination and confirmation of MLs and polycyclic aromatic hydrocarbons residue in food and water samples [60,61] (Table 1). Table 2 summarizes electronanalytical methods for determining chemical contaminants in food and biological samples using graphene-based electrochemical sensors. 3.2. Detection of food composition High cholesterol content in blood is one of the major controllable risk factors for coronary heart disease, heart attack, and stroke. Many foods contain cholesterol – animal brain, egg yolk, meat, seafood, and milk-based products are known for their high cholesterol content. Biosensors have been developed to determine cholesterol content in food. Cao et al. proposed a biosensor using TiO2– graphene–Pt–Pd nanocomposite coated with AuNPs. This biosensor was suitable for sensitive detection of cholesterol (0.017 μM) in foods (e.g., eggs, meat, margarine, and fish oil) [78]. Glucose is a fundamental energy nutrient, its concentration in the blood reflects the energy status of the body, and alteration of hypothalamic glucose in humans is associated with diabetes [79]. It is clinically important to do fast, accurate measurement of glucose concentration in biological or food samples. Highly crystalline manganese(II,III) oxide (Mn3O4) was deposited on a three-dimensional graphene foam (3DGF) to prepare a flexible, free-standing

Fig. 4. (A) The sensing process for phosphate-containing molecules based on a GQD@ GSH–Fe3+ probe. (B) Fluorescence emission spectra of GQD@GSH–Fe3+ (2 μg mL−1) in the presence of different ATP concentrations (0, 25, 50, 100, 250, 500, 1000, 2500, and 5000 μM). {Adapted with permission from [65]}.

time-dependent absorbance changes of the TMB–H2O2 system under different conditions. A small absorbance change in the system can be observed due to the slow reaction rate between TMB and H2O2 (Fig. 5B, curve a) [66]. Upon adding GO, the absorbance intensity of the system increased due to the intrinsic peroxidase property of GO, which can catalyze H2O2-mediated oxidation of TMB and produced the oxidation product with color change (Fig. 5B, curve c). GQDs have increased the absorbance intensity of the system (Fig. 5B, curve e) with the concentration of H2O2 from 10 nM to 0.5 mM. It is known that GSH can be converted into glutathione disulfide (GSSG) by reacting with H2O2. Using this strategy, GSSG was detected in the range 0.5–100 μM [66]. Bisphenol A (BPA), 2, 2-bis (4-hydroxyphenyl) propane, is a monomer in the production of epoxy resins and polycarbonates in polymer industry. BPA has been linked to the estrogenic adverse effects in human health. BPA has been used in food-packaging materials that come in direct contact with food products. Considering organic components of foodstuffs, non-polymerized monomer residues could be soluble in food products. A graphene-packed solidphase extraction (SPE) column was used to extract BPA from packed milk, yoghurt, and canned infant formula samples more effectively than commercial C18 from dairy samples [59] (Table 1). Macrolides (MLs) (e.g., lincomycin, azithromycin, tilmicosin, erythromycin and roxithromycin) are synthetic antibiotics used in animal husbandry, aquaculture, and human medicine. The presence of even a trace level of macrolides in food products would lead to side effects (e.g., allergic reactions, the appearance of resistant bacteria, and even cross-resistance to other antibiotics). Wu et al. used 2-D graphene as the sorbent to extract and to enrich MLs from fish samples by SPE. They found that graphene was a superior SPE sorbent for

Fig. 5. (A) The highly-efficient peroxidase-like activity of graphene dots (GQDs) for the detection of H 2 O 2 , glucose and reduced glutathione (GSH). (B) Time-dependent absorbance changes of the system under different conditions: (a) TMB (0.8 mM) + H 2 O 2 (50 mM); (b) GO (25 μg mL −1 ) only; (c) TMB(0.8 mM) + H2O2(50 mM) + GO (25 μg mL−1); (d) GQDs (25 μg mL−1) only; and (e) TMB(0.8 mM) + H2O2 (50 mM) + GQDs (25 μg mL−1). Adapted with permission from [66]}.

6.5–230 μM 5.0 × 10−8–2.0 × 10−5 mol L−1 Hemoglobin-Graphene/chitosan composite film β-cyclodextrin-coated/poly(diallyldimethylammonium chloride)-graphene composite film

GCE PET GCE SPCE

GCE GCE-RDE

Sudan I H2O2 H2O2 Ractopamine, Salbutamol and Clenbuterol H2O2 Sunset yellow (SY) and tartrazine (TT)

H2O2 ITO

GCE, Glassy carbon electrode; RDE, Rotatable disk electrode; SPCE, Screen-printed carbon electrode; PET, Polyethylene terephthalate; ITO, Indium tin oxide-coated glass; SDS, Sodium dodecyl sulfonate; rGO, Reduced graphene oxide. a These are based on electrochemical methods, except [69].

[76] [77] – Soft drinks

[72] [73] [74] [75]

4.0 × 10−8 mol L−1 1 μM 0.11 μM 1.52 pg mL−1, 1.44 pgmL−1 and 1.38 pg mL−1 5.1 × 10−7 M 1.25 × 10−8 mol L−1 for SY and 1.43 × 10−8 mol L−1 for TT 7.50 × 10−8–7.50 × 10−6 mol L−1 2 μM–6.5 mM 0.3 μM–1.8 mM 0.01–100 ng mL−1

Ketchup and chili sauce Serum, milk – Pork

[71] – 6.0 μM 0.1 × 10−3–1.5 × 10−3 mol L−1

Pickled radish Sea food sample Water and sewage samples 0.01 μM 0.19 ng mL−1 0.022 μg mL−1

Graphene-gold NPs-Hemoglobin hybrids Dipyridyl amine group/graphene nanosheets 7-[(2,4-dihydroxy-5-carboxybenzene)azo]-8hydroxyquinoline-5-sulfonic acid/graphene–Nafion composite (Poly(sodium 4-styrenesulfonate)/graphene sheets/ polyaniline)n film Graphene/SDS Mn3O4/3 D-graphene foam Hemin graphene nanosheets/AuNPs rGO and silver–palladium alloy NPs GCE Sorbent GCE

Sample matrix Limit of detection Linear range

0.05–1000 μM – 0.05–0.60 μg mL−1 Nitrite(NO2 ) Cd ions 2-Nitroaniline, 3-Nitroaniline, 4-Nitroaniline

−

Analyte Graphene and its composite Base electrode

Table 2 Graphene-based detection of chemical contamination in foodsa

[68] [69] [70]

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Ref.

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biosensor for non-enzymatic determination of glucose. Using Mn3O4/ 3DGF, Si et al. detected glucose in the range 0.1–8 mM with a high sensitivity of 360 μA mM cm−2 [73]. Generally, to retain the biological activity of glucose oxidase (GOD) on the electrode surface, it has to be immobilized on a biocompatible material that protects the native state of the enzyme, and that was possible using immobilized GOD on a graphene-AuNP film. The immobilized GOD displayed a couple of stable, well-defined redox peaks with an electron transfer rate constant of 3.25 s−1. Glucose was detected in the range 0.02–2.26 mmol L−1 using a graphene-Au biosensor with a high sensitivity (3.844 μA mmol L−1 cm−2) (Fig. 6A and B) [80]. β-lactoglobulin (BLG), which represents 10% of the proteins in cow’s milk, is considered the most important milk allergen, especially for children [82]. An amine-functionalized graphene surface was linked to anti-BLG antibodies using glutaraldehyde to detect BLG. In the presence of [Fe(CN)6]3-/4- in an aqueous solution, the peak current of [Fe(CN)6]3-/4- linearly decreased with increasing BLG concentration (from 1 pg mL−1 to 100 ng mL−1) due to the formation of antibody–antigen complex on the electrode surface [83]. A redox-active AuNP/poly(o-phenylenediamine)/graphene hybrid (AuNP-PG) was synthesized based on the π-stacking interactions between GNsh and the aromatic poly(o-phenylenediamine). This AuNP-PG film was used for labelling horseradish peroxidase (HRP) and detection of antibodies. With a sandwich immunoassay, target analytes (carcinoembryonic antigen, CEA) were quantitatively determined in the samples on the anti-CEA antibody-modified electrode. This electrochemical immunosensor displayed a wide dynamic range (0.005–80 ng mL−1) for CEA with a low LOD of 5 pg mL−1 [84]. Chen et al. reported that CEA antibodies could be conjugated onto the surface of AgNP–poly(o-phenylenediamine)–magnetic Fe3O4NPs through the interaction between AgNPs and the SH or NH2 groups of anti-CEA antibodies [85]. Electrochemical immunoassay of α-fetoprotein (AFP, as a model biomarker) was investigated by immobilizing anti-AFP antibody on an AuNP-functionalized-thionine graphene interface. Later, HRPanti-AFP (HRP-anti-AFP) conjugates were also immobilized on the AuNP surface (Fig. 6C). This electrochemical immunosensor displayed a wide dynamic range (0.1–200 ng mL−1) with an LOD of 0.05 ng mL−1 for AFP [81]. Recent findings demonstrated that aptamers (single-stranded nucleic acids isolated from random-sequence DNA or RNA) could be protected from DNase I cleavage after adsorption on the graphene surface [86]. It is possible to get an amplified assay based on the use of an aptamer and graphene by first incubating the carboxyfluorescein-labelled adenosine triphosphate (ATP) aptamer (50 nM) with graphene to form an aptamer–graphene complex. After adding of ATP and DNase I simultaneously, highly amplified 330 ± 9% fluorescence intensity was observed. This amplified aptamerbased assay is sensitive and highly specific, and can detect ATP concentrations down to 40 nM [86]. A molecular beacon biosensor using GO as the “nanoquencher” (Fig. 7A) was fabricated. GO has a quenching effect on the fluorescence of a fluorescein-labelled-hairpin (HP)-structured oligonucleotide up to 99.1%. Observation indicated strong adsorption of the HP-structured oligonucleotide on the GO, and the exceptional fluorescence-quenching effect of GO [87,89]. The fluorescence intensity of fluorescein amidite (FAM)-labelled HP–GO changes upon addition of different concentrations of target (T1). An increase in FAM fluorescence intensity was observed at target DNA concentrations of 5–500 nM (LOD ~2.0 nM), which is 16fold lower than that of the conventional FAM-labelled molecular beacons [87]. Bovine hemoglobin (BHb)-imprinted polydopaminefunctionalized rGO (PDA@rGO) was prepared by Luo et al. By simply immersing GO in a weak alkaline solution of dopamine containing BHb, a thin, adherent polydopamine (PDA) film imprinted with

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Fig. 6. (A) Amperometric responses of the (GOD–graphene–AuNPs)5/GCE at 0.6 V upon successive additions of glucose to air-saturated PBS (pH 7.0) with stirring. Inset: calibration curve between current and cglucose. (B) The Lineweaver-Burk plots for the (GOD–graphene–AuNPs)5/GCE with glucose as a substrate. {Adapted with permission from [80]}. (C) Electrochemical immunosensor and one-step measurement protocol for detection of α-fetoprotein. {Adapted with permission from [81]}.

BHb was obtained on the surface of GNsh to produce the BHbimprinted PDA@rGO nanomaterial, which displayed much higher binding capacity toward BHb than control PDA@rGO because of nonspecific adsorption at the surface [90]. GO can also distinguish single-stranded DNA (ss-DNA) from double-stranded DNA (ds-DNA) because of its significantly different adsorption affinities to ss-DNA and ds-DNA [91]. Based on the specific binding ability of graphene, a colorimetric method for detection of DNA damage was developed using hemin-GNsh (HGNsh), which possesses the ability of graphene to differentiate damaged DNA from intact DNA in the range 5–60 nM with an LOD of 1 nM [92]. Wu et al. demonstrated direct electron transfer of GOD on the TiO2-graphene nanohybrid film with a rate constant of 3.24 s−1. Based on the decrease in electrocatalytic response to dissolved oxygen, glucose concentration was measured in the range 5 × 10 −4 – 2 × 10−2 mol/L with an LOD of 1.7 × 10−4 mol/L [93]. Electrochemical impedance spectroscopy (EIS)-based methods are extensively used to study biological events occurring at the electrode surface (e.g., cell growth, protein binding, bacterial growth, DNA hybridization, and antigen-antibody reaction) [94]. Hou et al [88]. used graphene-based nanocomposites as an efficient

platform for biomolecule recognition and reaction to study and to improve analytical sensitivity and selectivity. They developed a GObased method to detect CEA by coupling with enzymatic biocatalytic precipitation of 4-chloro-1-naphthol (4-CN) on the captured antibody-modified GCE with HRP. Antibodies and HRP molecules were covalently attached onto the surface of GO nanosheets through the carbodiimide coupling. In the presence of 4-CN and H2O2 in solution, the HRP enzyme could catalyze 4-CN and yield an insoluble benzo-4-chlorohexadienone product, which simultaneously deposited on the surface of the impedimetric immunosensors, thus hindering the electron transfer process of the redox probes between the base electrode and the solution. The electron-transfer resistance (Ret) increased with increasing CEA concentration in the sample in the range 1.0 pg mL−1–80 ng mL−1 (Fig. 7B). The selectivity of this method was tested with other low-abundance proteins [e.g., AFP, prostate-specific antigen (PSA), and human IgG]. Results showed that low signals toward these components observed at only higher concentrations than the target analyte. This method could be useful for highly specific detection of CEA (Fig. 7C). Salbutamol, [2-(tert-butylamino)-1-(4-hydroxy-3-hydroxymethyl) phenylethanol] is a widely used β-adrenergic receptor agonist, which induces bronchodilation, making the drug very useful for curing

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Fig. 7. (A) Target-induced fluorescence change of GO-quenched molecular beacon. {Adapted with permission from [87]}. (B) Calibration plots of the impedimetric immunosensor (log C vs. Ret) for target CEA from 1.0 pg mL−1 to 80 ng mL−1(error bars: SD, n = 3) by using HRP-GO-Ab2 [Inset: (top) Nyquist diagrams for the impedimetricimmunosensors by using HRP–GO–Ab2 toward CEA standards with various concentrations in pH 7.4 PBS containing 5.0 mM Fe(CN)64−/3−and 0.1 M KCl; (bottom) Calibration plots of the impedimetric immunosensor by using HRP–Ab2, and (C) resistance changes of the impedimetric immunoassay against AFP, PSA and human IgG. {Adapted with permission from [88]}.

bronchial asthma, chronic obstructive pulmonary disease and other allergic diseases of the respiratory pathway. It is a prohibited substance with high dose values in sports because it acts as a stimulant and an anabolic agent [95]. An assay of salbutamol (SAL) is very important for animal tissues and biological fluids [96]. An ultrasensitive immunosensor was based on AuNPs, Prussian blue, polyaniline/poly (acrylic acid) and Au-hybrid graphene nanocomposite (AuGN). An AuGN film was used to immobilize chitosan and HRP–anti-SAL antibody (HRP–AAb). The resulting nanostructure (AuGN–HRP–AAb) was used as a label for the immunosensor. The high surface area-to-volume ratio of graphene allows the immobilization of a high level of chitosan, AuNPs and HRP–AAb, and its good electrical conductivity (and biocompatibility) improved electron transfer among HRP, H 2 O 2 , and electrode. This graphene-based immunosensor showed a linear plot for SAL in the range 0.08–1000 ng/mL with an LOD of 0.04 ng/mL [97]. Squamous cell carcinoma antigen (SCC-Ag) was first found in the uterine cervical SCC and the serum level of SCC-Ag parallels the growth of the tumor size [98]. For diagnosis, it is clinically important to measure the serum level of SCC-Ag. Li et al. developed a magneto-controlled microfluidic device for the detection of SCCAg in serum by using anti-SCC antibody (SCC-Ab)-functionalized magnetic mesoporous nanogold/thionine/NiCo 2 O 4 hybrid nanostructures as immunosensing probes (P1-Ab) and HRP-SCCAb conjugate-labelled nanogold/GNsh as signal tags (P2-Ab) [99] (Fig. 8A). Studies suggest that chemical substances stimulate estrogenic activity and cause adverse effects in humans and animals or environmental organisms [101]. It was found that steroid estrogens re-

leased from humans are the main causal agents in the feminization of fish in the aquatic environment [102]. The main chemicals causing these effects are natural compounds, estrone (E1), estradiol (E2) and estriol (E3), and synthetic estrogens. Detection of estrogens is important in order to assess and to predict the estrogenic potency of foods or surface waters. Fe3O4-NPs with a composite made from TiO2 and GO ((Fe3O4@TiO2/GO) were used to extract estrogens E1, E2, and E3 from milk samples. The estrogens were then eluted from the beads with methanol and analyzed with HPLC [58] (Table 1). 3.2.1. Graphene-based ion-selective electrodes The ion-selective electrode (ISE) is a transducer that converts the activity of a specific ion dissolved in a solution into an electrical signal (potential). The voltage theoretically depends on the logarithm of ionic activity, according to the Nernst equation. The sensing part of the electrode is usually an ion-specific membrane, along with a reference electrode. Elimination of the internal filling solution from conventional ISEs results in solid-contact ISEs or ion-sensitive sensors (ISSs), which are more durable and easier to miniaturize than their conventional counterparts [103]. Graphene-based paper was obtained by vacuum filtration of graphene suspension and directly used as a free-standing electrode substrate in all solid-state ISEs (Fig. 8B) [100]. The potentiometric voltage signals of three free-standing grapheme-paper (GNP) ISEs (i.e., GNP/K-ISE, GNP/Ca-ISE, and GNP/H-ISE) were recorded after successive additions of the primary analyte to the test solution. All the signals were stable, with no obvious perturbations or random noise after each addition, and the response times were less than 40 s indicating that the GNP is a good electrode candidate [100].

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Fig. 8. (A) Immunoassay protocol of (a) the magneto-controlled electrochemical microfluidic device, (b) bioconjugation of magnetic mesoporous nanogold/thionine/ NiCo2O4 nanostructure with SCC-Ab, and (c) bioconjugation of nanogold/graphene nanosheet with HRP-SCC-Ab [Adapted with permission from Ref. (83)]. (B) The fabrication process of a graphene paper (GNP)-based potentiometric sensing device: (a) oxidation and exfoliation, (b) reduction, (c) filtration, (d) cutting, (e) coating, (f) assembling, (g) dip coating, and (h) detecting. {Adapted with permission from [99]}.

Ping et al. developed a disposable all solid-state ISE using graphene as the ion-to-electron transducer. The graphene film was prepared on a screen-printed electrode (SPE) directly from GO dispersion by a one-step electrodeposition technique [104]. A solidstate calcium ISE was constructed using a calcium ISE membrane and a graphene film-modified electrode. A stable voltage signal was recorded after each successive addition of Ca2+ to the test solution without any perturbations or random noise. The response was almost Nernstian, displaying a slope of 29.1 mV/decade with a linear range of 10−5.6–10−1.6 M of Ca2+, and an LOD of 10−5.8 M. Furthermore, the response time was much faster (≤10 s) than that of electrodes that contain a similar membrane with liquid contact [104]. This graphenebased ISE was tested as a disposable potentiometric sensor to determine Ca2+ content in milk and beverage samples.

3.3. Detecting volatile organic compounds Using miniaturized electrochemical and electronic devices, there have been applications of graphene nanomaterials in different fields of analysis (e.g., environmental monitoring, clinical diagnosis and nanomedicine) [105]. Recently, sensing skins made of rGO-based quantum resistive vapor sensors (vQRS) were developed [106]. Graphene-based sensors are assembled into arrays to make e-noses to analyze the nature and the content of volatile organic compounds (VOCs) released by food in the package headspace. To fabricate VOC sensors, rGO–ionic liquid polymers (PILs) and rGO–PIL/ poly(3,4-ethylenedioxythiophene) composite powders were dispersed in acetone. Using a home-made device [107], the corresponding solution was sprayed layer-by-layer onto inter-digitated

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A.K. Sundramoorthy, S. Gunasekaran/Trends in Analytical Chemistry 60 (2014) 36–53

Fig. 9. (a) Response of graphene-based sensors to methanol concentration from 1000 to 2.5 ppm. (b) Pattern recognition of the e-nose exposed to some meat VOC markers after principal component analysis (PCA). {Adapted with permission from [106]}.

electrodes. The vapor-sensing characteristics of graphene and its nanocomposites with poly(thiophene) were tested by recording their chemoresistive responses at room temperature upon exposure to flows of pure nitrogen and VOCs. Methanol, ethanol, acetone, methyl acetate, dimethylsulfide and toluene vapors were tested because they are released from meat [108], fruits [109], and vegetables [110], so they could be considered as markers of food deterioration. The resistance relative amplitude or relative differential resistance responses (Ar) of sensor devices were recorded and defined as Ar = (R–Ro)/Ro, where R is the resistance of the sensing materials in the presence of exposed vapors and Ro is resistance of the sensing materials under a nitrogen flow. In Fig. 9a, the vapor content was decreased from 1000 parts-per-million (ppm) to 2.5 ppm for methanol. Based on the two first principal components (PC1 and PC2), accounting for 98.25% of the total variance (Fig. 9b) [106], the six clusters of points corresponding to different VOC markers appear well separated from each other, confirming that rGO-based sensors could simultaneously detect and identify the selected vapors. 4. Food safety 4.1. Extraction and detection of toxins Lipophilic marine toxins (LMTs) {okadaic acid and its derivatives [dinophysistoxin-1 (DTX-1), dinophysistoxin-2 (DTX-2) and

dinophysistoxin-3 (DTX-3)]} are produced by several microalgae species and frequently bio-accumulated in filter-feeding molluscan shellfish (e.g., mussels, oysters and clams) [111]. Consumption of phycotoxin-contaminated marine products may cause severe intoxication in humans (e.g., diarrhetic shellfish poisoning, which is a common syndrome around the world and results in adverse effects, such as, gastrointestinal disorder, diarrhoea, abdominal cramps, nausea and vomiting) [112,113]. Shen et al. investigated the potential of graphene as an SPE sorbent for purifying LMTs [114]. The performance of graphene was compared with that of several other sorbents or commercial SPE cartridges, including C18, MWCNTs, hydrophilic-lipophilic balance and Strata-X. This method was also applied to analyze the tissue from commercially available shellfish. The best extraction efficiencies were obtained with graphene as PT-SPE sorbent, followed by commercial Strata-X. The extraction efficiencies of about 90% achieved with graphene were attributed to its double-sided polyaromatic scaffold structure, which afforded it ultrahigh specific surface area and high loading capacity. This graphene-based sorbent showed excellent specificity, linearity, reproducibility, high extraction efficiency, and low LOD. GO has also been used for extraction and quantification of aflatoxins in peanuts with extraction efficiency greater than 85% by HPLC (Table 1) [57]. Mycotoxins are secondary metabolites produced by fungi and are capable of causing disease and death in humans and other animals [115]. Multicolor upconversion fluorescent NPs doped with erbium (Er) and thulium (Tm) were synthesized as donors together with GO as the effective acceptor. Wu et al. developed a multiplexed fluorescence resonance energy transfer (FRET)-based turn-on assay for the simultaneous detection of two types of mycotoxins (ochratoxin A, OTA and fumonisin B1, FB1) [116]. This aptasensor provided linear ranges of 0.05– 100 ng·mL−1 for OTA and 0.1–500 ng·mL−1 for FB1; the LODs for OTA and FB1 were 0.02 ng·mL−1 and 0.1 ng·mL−1, respectively. When naturally contaminated maize samples were tested, the results obtained with this sensor were consistent with those with an enzymelinked immunosorbent assay (ELISA). Brevetoxin B (BTX-2) is a neurotoxin produced by algae Karenia brevis. Consumption of brevetoxin-contaminated shellfish can cause intoxication and even death, and cause respiratory irritation through aerosol exposure in coastal areas [117]. Tang et. al [118]. used monoclonal mouse anti-BTX-2 antibodies covalently immobilized on the surface of magnetic beads as immunosensing probes for detecting BTX-2. The recognition elements were prepared by chemical modification of bovine serum albumin-BTX-2 conjugates (BSA-BTX-2) with the guanine-functionalized graphene nanoribbons (G-GNRs). This method is proposed for detection of BTX-2 in seafood and other foodstuffs as it can detect BTX-2 concentrations as low as 1.0 pg mL−1. In general, graphene-based analytical methods afford exceptional sensitivity and ultralow LODs for various biomolecules (Table 3). 4.2. Detection of pesticides Pesticides (e.g., pymetrozine, thidiazuron, diuron, carbofuran, carbaryl, pirimicarb, diethofencarb, procymidone, folpet, vinclozolin and ditalimfos) are commonly used in agriculture to thwart diseases [51,52]. Use of these chemicals has proved very effective, but several concomitant risks remain. The pesticide residues in foods adversely affect human health because of their high biological activity and inherent toxicity. The US Environmental Protection Agency (EPA) lists 12 of the 26 most widely used pesticides in the USA as carcinogens. Improper and excessive use of these pesticides lead to them being slowly accumulated in the food chain; these poisonous chemicals also contaminate natural water sources [134]. According to the Council of the European Union, the total maximum

Base electrode

Graphene and its composite

Analyte

Linear range

Limit of detection

Sample matrix

Ref.

Natural aloe extracts and human urine Pork

[119]

GCE

Graphene-Nafion film

Aloe-emodin (antitumor herbal drug)

5 nmol/L–1 μmol/L

2 nmol/L

GCE

4,5-dihydroxy-3-[(2-hydroxy-5-sulfophenyl)azo]-2,7naphthalenedisulfonic acid/GO-Nafion film

1.0–36.0 ng mL−1

0.58–1.46 ng mL−1

GCE ITO GCE PET SPE GCE GCE GCE

Fe3O4-functionalized graphene nanoribbons rGO/AuNPs Nickel hexacyanoferrate/rGO Mn3O4/3 D-graphene foam Chitosan-rGO–NiNPs GOD-Au-Ag hollow microspheres/Prussian blue NPs/graphene Graphene-Nafion/thionine/Pt-NPs+antikanamycin antibody Graphene oxide (GO)

Clenbuterol, salbutamol, terbutaline, ractopamine, dopamine, dobutamine, adrenaline, and isoprenaline Dopamine Dopamine Glucose Glucose Glucose Carcinoembryonic antigen (CEA) Kanamycin Ractopamine and Clenbuterol

1–30 μM 10 to 1000 μM 1.0 × 10−6–1.7 × 10−2 M 0.1–8 mM 0.2 to 9.0 mM 0.005–50 ng mL−1 0.01–12.0 ng/mL 25 μg L−1–1 mg L−1

– Meat Human blood serum Serum, milk Urine samples Clinical serum specimens Chicken liver Pork samples

[121] [122] [123] [73] [124] [125] [126] [127]

GCE Au

GOD-rGO–AuPd alloy NP composites Thionine-Nanogold-magnetic beads (signal tags)/nanogold– graphene + HRP-anti-TSH conjugates Nanogold- magnetic graphene nanosheet+ HRP-anti-AFP conjugates Graphene/Prussian blue-chitosan/nanoporous gold + Kanamycin antibody Carbon nanospheres-graphene-platinum nanosphere + labeled HRP-anti-CEA conjugates Graphene-Anti-CEA antibodies -Pt@Aunano labels + GOD + glucose–hydroquinone system

Glucose Thyroid-stimulating hormone

0.5–3.5 mM 0.01–20 μIU mL−1

0.33 μM 6.0 × 10−8 M 2.8 × 10−7 M 10 μM 4.1 μM 1.0 pg mL−1 5.74 pg/mL 17 μg L−1(5.6 × 10−8 M) and 15 μg L−1(4.8 × 10−8 M)for ractopamine and clenbuterol. 6.9 μM 0.005 μIU mL−1

Human blood serum Human serum specimens

[128] [129]

α-fetoprotein

0.01–200 ng mL−1

1.0 pg mL−1

Human serum

[130]

Kanamycin

0.02–14 ng mL−1

6.31 pg mL−1

Pork

[131]

CEA

0.001–100 ng mL−1

1.0 pg mL−1

Clinical serum samples

[132]

CEA

0.001–120 ng mL−1

0.5 pg mL−1

Serum specimens

[133]

Au disk electrode GCE GCE GCE

[120]

A.K. Sundramoorthy, S. Gunasekaran/Trends in Analytical Chemistry 60 (2014) 36–53

Table 3 Graphene-based detection of biomolecules in foods

GOD, Glucose oxidase; HRP, Horseradish peroxidase; SPE, Screen-printed electrode.

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admissible concentration of pesticides is no more than 0.5 μg L–1 [135]. Wang et al [136]. developed a graphene-based magnetic nanocomposite as the adsorbent for the extraction of seven triazole fungicides (triadimefon, paclobutrazol, hexaconazole, myclobutanil, diniconazole, propiconazole, and tebuconazole) in cucumber, cabbage, and tomato samples prior to gas chromatography–mass spectrometry (GC-MS) detection. The LODs for the analytes were 0.01–0.10 ng g−1. However, monitoring lipophilic pesticides at trace levels is challenging, and extensive sample extraction and cleanup procedures were required [137]. Common methods [e.g., liquidliquid extraction (LLE) and SPE] were required to pre-concentrate trace analytes from environmental or food samples [138]. However, LLE requires large amounts of organic solvents and SPE is considered very tedious. Graphene was used as an adsorbent in LLE and SPE to pre-concentrate and to extract pesticide compounds in environmental samples due its extremely large surface area and excellent adsorption capacity. Guan et al [51]. proposed to use amine-modified graphene to clean up fatty acids and other interfering substances from acetonitrile extracts of oil crops. This amine-modified graphene was the best of the tested sorbents as a reversed-dispersive SPE (r-DSPE) clean-up sorbent and was used effectively to determine 31 pesticides in oil crops (Table 1). Li et al [52]. proposed another method based on magnetic particle-modified adsorbents in magnetic SPE (MSPE), which offered a simple way to extract analytes (fungicides) from contaminated samples without extensive centrifugation and filtration steps. In some cases, a magnetic graphene nanocomposite (G-Fe3O4) was used as the adsorbent to extract fungicides from water and grape-juice samples to be analyzed with GC (Table 1). Zhao et al. extended the study on G-Fe3O4 magnetic NPs (G-Fe3O4 MNPs) for the MSPE of some triazine herbicides (atrazine, prometon, propazine and prometryn) in water. After the extraction, the adsorbent could be conveniently separated from the aqueous samples by an external magnet and almost complete desorption of the analytes from the sorbent could be achieved using acetone as desorption solvent. The sensitivity of the method is better than that of the other MSPE methods that do not use graphene. In addition, the G-Fe3O4 is a very efficient adsorbent and it could be reused for at least 15 times without a significant decrease in extraction efficiency [55]. GNsh-coated SPME fiber was also prepared by immobilizing GNsh on a stainless-steel wire. The extraction efficiency of the GNshSPME method was better for five organochlorine pesticides (OCPs) [1,1-dichloro-2,2-bis-(p’-chlorophenyl)ethylene, 1,1-dichloro-2,2bis-(p’-chlorophenyl)ethane, 1,1,1-trichloro-2,2-bis(p’-chlorophenyl) ethane, dieldrin and endrin) [53], and carbamate pesticides (carbofuran, carbaryl, pirimicarb, and diethofencarb) [54], compared with the conventional water-bath microwave-assisted headspace-SPME method (Table 1). For further information, there are recent review articles on sample preparation using metallic NPs [139] and carbon nanomaterials [140].

a), and colony counting showed that less than 10% of E. coli survived (Fig. 10A, b). TEM studies revealed that rGO nanosheets destroyed the cell membrane of E. coli (Fig. 10A, c). However, the cell viability of A549 (a mammalian cell line) was reduced to ~47% and ~15% with rGO nanosheets of 20 μg/mL and 85 μg/mL, respectively (Fig. 10A, d) [143]. The antibacterial effect of rGO nanosheets was less than that of GO nanosheets, while the cytotoxicity of rGO nanosheets was significantly greater than that of GO nanosheets. The mechanism of such irreversible GO-induced or rGO-induced cellular damage of E. coli might arise from the effects of oxidative stress or their cell membrane being damaged by direct contact with very sharp edges of graphene sheets [141,143]. Chook et al. synthesized AgNPs on GO with a narrow size distribution using a microwave-irradiation method [145]. Both AgNPs and Ag-GO samples exhibited antibacterial activity that was stronger against Gram-negative than against Gram-positive bacteria. They reported that the antibacterial performance using Ag-GO with a lower concentration of Ag was better than using AgNPs. Thus, the synergistic effect between GO and AgNPs allows use of a smaller amount of AgNPs without compromising the antibacterial properties. This alleviates concerns about excessive Ag usage, and makes Ag-GO composite a potential material for food packaging and wounddressing applications [145]. As a result of the overuse of antibiotics, several human pathogenic bacteria have become resistant to most clinically approved antibiotics. This has created an urgent need to develop new methods to kill pathogenic bacteria. A method for selective killing of pathogenic bacteria using antibody-functionalized rGO is proposed. The anti-Staphylococcus aureus (S. aureus) polyclonal antibody (pAb)– rGO complex exhibited little toxicity without near-infrared (NIR) irradiation. However, when irradiated with an NIR laser at low power density (400 mW cm−2), the antibody–rGO complex exhibited excellent photothermal properties and killed captured pathogenic bacteria specifically. The pAb adsorbed rGO can readily and specifically bind to S. aureus through antibody–antigen recognition. Under irradiation with NIR, rGO absorbs more NIR, and it converted light into heat effectively, which destroys S. aureus by excessive local heating (Fig. 10B) [144]. Bio-functionalized graphene film was prepared by the chemical reduction of GO using a nitrene chemistry, and then chitosan was covalently grafted onto the graphene surface. The mechanical properties and the electrical conductivity of the composite film dramatically improved, because of the strong interfacial bonds between the homogeneously dispersed chitosanfunctionalized graphene and the chitosan matrix. The effectiveness of the bio-functionalized graphene as a reinforcing filler (4 wt%) in a chitosan polymer matrix is verified by the dramatic enhancement of the mechanical properties (breaking stress = 330%, Young’s modulus = 243%) and the electrical conductivity (0.3 S m−1) without much loss in the elongation-at-break. In addition, this strong graphene-filled composite film could be used as an antimicrobial packaging material for food and biomedical devices [146].

4.3. Antibacterial properties of graphene

5. Summary

It has been shown that GO possesses antibacterial properties against Escherichia coli (E. coli) [141]. In addition, enhanced antibacterial properties have been observed on Ag-functionalized graphene materials [142]. Hu and co-workers proved that water-dispersible graphene derivatives, GO and rGO nanosheets could effectively inhibit the growth of E. coli while showing minimal cytotoxicity [143]. After 2 h incubation with GO nanosheets of 20 μg/mL at 37°C, the cell metabolic activity for E. coli decreased from ~70% to ~13%. In the same way, the metabolic activity of E. coli DH5α cells was reduced to ~24% on treatment with rGO nanosheets of 85 μg/mL at 37°C for 2 h (Fig 10A,

High-quality graphene or graphene-based metal nanocomposites can be synthesized for various applications using carbon source materials, including foodstuffs, by the CVD method [26–30]. Graphenebased nanomaterials have been successfully employed (e.g., electrochemical sensors, biosensors, and immunosensors to detect constituents and contamination in foods, food packaging as antibacterial coating, and DNA detection). In particular, graphene, GO, and rGO, when used in chemical sensors and biosensors, have shown much promise in food analyses in terms of improvements in sensitivity, LOD, selectivity, and simultaneous detection of multiple analytes (Tables 2,3). In particular, standard and simple Raman

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Fig. 10. (A) Antibacterial activity and cytotoxicity of rGO nanosheets. (a) Metabolic activity of E. coli treated with 85 μg/mL GO and rGO nanosheets, respectively. (b) Antibacterial activity of 85 μg/mL GO and rGO nanosheets against E. coli. (c) TEM image of E. coli exposed to 85 μg/mL rGO nanosheets at 37°C for 2 h. (d) Viability of A549 cell incubated with 20 μg/mL and 85 μg/mL rGO nanosheets, respectively. {Adapted with permission from [143]}. (B) (a) The photothermal therapy process using AbNRGO, and (b) colonies of S. aureus before (A) and after (B) exposure to light with 400 mW cm−2 power for 10 min in the presence of Ab–NRGO. {Adapted with permission from [144]}.

spectrum of graphene derivatives allowed them to be used as a SERS substrate for highly sensitive identification and detection of organic contamination {e.g., RhB [34], amaranth, erythrosine, lemon yellow, sunset yellow [36], and aminothiophenol [35]}. Further improvements in sensitivity and LOD are possible when graphene is hybridized with AgNPs. When mixed with a metal catalyst (e.g., PtNPs, PdNPs, TiO2, and Mn3O4), graphene offers substantial improvements in electrocatalytic oxidation or reduction of electroactive oxalic acid [41], H2O2 [43,63], glucose [73], SY, TT [47], Sudan I and Orange II [48,49], malachite green [62], and mercury(II) [64]. GQDs exhibit low toxicity, and high solubility and photoluminescence. Taking advantage of these properties, a fluorescence “off-to-on”-based method was developed for assaying ATP [65] and GSSG [66]. The highly hydrophobic nature of graphene was utilized in the extraction of BPA [59] and macrolides [60] (e.g., from packed milk, infant formula samples, and fish

samples). A graphene-packed SPE column effectively enriches molecules of interest and enables their detection with coupled analytical techniques, such as chromatography [61]. TiO2–graphene–Pt–Pd-AuNP nanocomposites with ChOx were developed for detection of cholesterol content in food samples [78], and GOD was immobilized on the graphene-modified electrodes with AuNPs or TiO2; these sensors detected glucose with high sensitivity [80,93]. Antibody-modified graphene film was used to detect milk protein β-lactoglobulin [83] and CEA [84], and α-fetoprotein [81]. Using the fluorescence-quenching effect of GO, DNA was detected from 5 nM with LOD of 2 nM [86]. Also, a GObased colorimetric method was developed for detecting damaged DNA [92]. GO-modified electrodes were functionalized with various antibodies and employed as electrochemical immunosensors. CEA protein could be detected effectively by changes in the

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electron-transfer resistance after chemical reactions [88]. Graphenebased hybrid film with AuNPs/PB/HRP-AAb was used for the detection of salbutamol from 0.08 ng/mL [97]. Graphene functionalized with magnetic mesoporous nanogold/thionine/NiCo2O4 was developed for detection of SCC-Ag in serum [99]. GO combined with Fe3O4@TiO2 has been used to extract estrogens from milk samples. After extraction, the eluted estrogens were successfully analyzed with HPLC [58]. A graphene-based paper electrode was prepared and used as electric conductor and Ca2+ ISE [100,104]. Also, graphene-based sensor arrays were used as e-noses to detect and to analyze the VOC content released from packaged foods [106]. Graphene has been used as an SPE sorbent for effective extraction and purification of LMTs [114], mycotoxins [116], neurotoxins [118], pesticides [51,53,55], fatty acids in food and environmental samples [51]. Graphene or graphene modified with metal-oxide NPs improves extraction efficiency, compared to common sorbents (e.g., C18, MWCNTs and Strata-X) because of the polyaromatic structure of graphene derivatives and their extremely large active surface area. Using graphene as adsorbent, we could eliminate extensive use of solvent in the extraction of mycotoxins or pesticides, as required for the conventional LLE method. The graphene-based sorbent could be reused several times without decrease in extraction efficiency. Antibacterial properties of GO and rGO have been demonstrated against E. coli with minimal cytotoxicity [143]. When GO was mixed with AgNPs, it exhibited stronger antibacterial activity against Gram-positive bacteria than AgNPs alone [145]. Also, antibody-functionalized rGO is proposed for selective killing of pathogenic bacteria with NIR irradiation. rGO absorbs more light and converts it into heat effectively to kill adsorbed bacteria [144]. Recently, a composite film of chitosan functionalized graphene with chitosan matrix showed strong mechanical properties without loss in elongation-at-break. This hybrid film has potential to be used as a packaging material for foodstuffs [146]. 5.1. Outlook and challenges Impressive research trends in graphene and graphene derivatives may lead to development of miniaturized electrochemical and electronic devices for real-time monitoring and analyses of food quality. However, synthesis of pure single-layer graphene (without residual oxygen groups on the surface) is still challenging and pure single-layer graphene could be produced only in limited quantity by the CVD process, so relatively increasing the cost of the product. Although we could produce large quantities of rGO (with residual oxygen groups on the surface) from GO by chemical, thermal or electrochemical reduction, the electrical/chemical properties of rGO may differ significantly, depending on the method used for exfoliation and reduction. From the environmental point of view, the current GO-production method (modified Hummers) will produce extensive acid wastes, and the synthesis involves handling dangerous acids with the risk of explosion [147]. Also, the morphology and the chemical structure of rGO are very sensitive to the method of synthesis, and will significantly affect the performance of the final graphenebased sensor devices. It is therefore necessary to produce highquality, single-layer graphene inexpensively and large quantities for any commercialization of graphene-based analytical or separation technology. Graphene is transparent, flexible, biocompatible and thermally stable, so we may expect that graphene-based materials will find increased application in food packaging and labelling. However, the health and safety consequences of graphene in food-packaging materials coming into direct contact with foodstuffs is still a concern, so use of graphene in the food industry will probably become an active area of research.

References [1] N. Duran, P.D. Marcato, Nanobiotechnology perspectives. Role of nanotechnology in the food industry: a review, Int. J. Food Sci. Tech. 48 (2013) 1127–1134. [2] H.F. Wang, L.J. Du, Z.M. Song, X.X. Chen, Progress in the characterization and safety evaluation of engineered inorganic nanomaterials in food, Nanomedicine 8 (2013) 2007–2025. [3] T.V. Duncan, Applications of nanotechnology in food packaging and food safety: barrier materials, antimicrobials and sensors, J. Colloid Interface Sci. 363 (2011) 1–24. [4] X.X. Chen, B. Cheng, Y.X. Yang, A.N. Cao, J.H. Liu, L.J. Du, Y.F. Liu, Y.L. Zhao, H.F. Wang, Characterization and preliminary toxicity assay of nanotitanium dioxide additive in sugar-coated chewing gum, Small 9 (2013) 1765–1774. [5] A. Jaeger, D.G. Weiss, L. Jonas, R. Kriehuber, Oxidative stress-induced cytotoxic and genotoxic effects of nano-sized titanium dioxide particles in human HaCaT keratinocytes, Toxicology 296 (2012) 27–36. [6] B.A. Magnuson, T.S. Jonaitis, J.W. Card, A brief review of the occurrence, use, and safety of food-related nanomaterials, J. Food Sci. 76 (2011) R126-R133. [7] B. Pérez-López, A. Merkoçi, Nanomaterials based biosensors for food analysis applications, Trends Food Sci. Technol. 22 (2011) 625–639. [8] S. Lim, O.K. Koo, Y.S. You, Y.E. Lee, M.S. Kim, P.S. Chang, D.H. Kang, J.H. Yu, Y.J. Choi, S. Gunasekaran, Enhancing nanoparticle-based visible detection by controlling the extent of aggregation, Sci. Rep. 2 (2012) 456. [9] C. Wang, C.X. Yu, Detection of chemical pollutants in water using gold nanoparticles as sensors: a review, Rev. Anal. Chem. 32 (2013) 1–14. [10] A.K. Singh, D. Senapati, S. Wang, J. Griffin, A. Neely, P. Candice, K.M. Naylor, B. Varisli, J.R. Kalluri, P.C. Ray, Gold nanorod based selective identification of Escherichia coli bacteria using two-photon Rayleigh scattering spectroscopy, ACS Nano 3 (2009) 1906–1912. [11] I.-H. Cho, J. Irudayaraj, In-situ immuno-gold nanoparticle network ELISA biosensors for pathogen detection, Int. J. Food Microbiol. 164 (2013) 70–75. [12] H.Q. Chen, B. Wang, D. Gao, M. Guan, L.N. Zheng, H. Ouyang, Z.F. Chai, Y.L. Zhao, W.Y. Feng, Broad-spectrum antibacterial activity of carbon nanotubes to human gut bacteria, Small 9 (2013) 2735–2746. [13] A.K. Geim, K.S. Novoselov, The rise of graphene, Nat. Mater. 6 (2007) 183–191. [14] L.M. Dai, Functionalization of graphene for efficient energy conversion and storage, Acc. Chem. Res. 46 (2013) 31–42. [15] K. Yan, L. Fu, H. Peng, Z. Liu, Designed CVD growth of graphene via process engineering, Acc. Chem. Res. 46 (2013) 2263–2274. [16] D.C. Marcano, D.V. Kosynkin, J.M. Berlin, A. Sinitskii, Z. Sun, A. Slesarev, L.B. Alemany, W. Lu, J.M. Tour, Improved synthesis of graphene oxide, ACS Nano 4 (2010) 4806–4814. [17] C.-Y. Su, A.-Y. Lu, Y. Xu, F.-R. Chen, A.N. Khlobystov, L.-J. Li, High-quality thin graphene films from fast electrochemical exfoliation, ACS Nano 5 (2011) 2332–2339. [18] P. Avouris, C. Dimitrakopoulos, Graphene: synthesis and applications, Mater. Today 15 (2012) 86–97. [19] N.O. Weiss, H.L. Zhou, L. Liao, Y. Liu, S. Jiang, Y. Huang, X.F. Duan, Graphene: an emerging electronic material, Adv. Mater. 24 (2012) 5782–5825. [20] K.C. Kemp, H. Seema, M. Saleh, N.H. Le, K. Mahesh, V. Chandra, K.S. Kim, Environmental applications using graphene composites: water remediation and gas adsorption, Nanoscale 5 (2013) 3149–3171. [21] M. Valdés, A. Valdés González, J. García Calzón, M. Díaz-García, Analytical nanotechnology for food analysis, Microchim. Acta 166 (2009) 1–19. [22] B.S. Sekhon, Food nanotechnology – an overview, Nanotechnol. Sci. Appl. 3 (2010) 1–15. [23] C.A. Damalas, I.G. Eleftherohorinos, Pesticide exposure, safety issues, and risk assessment indicators, Int. J. Environ. Res. Public Health 8 (2011) 1402–1419. [24] Z. Huang, H.K. Lee, Materials-based approaches to minimizing solvent usage in analytical sample preparation, Trac Trends Anal. Chem. 39 (2012) 228–244. [25] R. Muñoz, C. Gómez-Aleixandre, Review of CVD synthesis of graphene, Chem. Vap. Deposition 19 (2013) 297–322. [26] G. Ruan, Z. Sun, Z. Peng, J.M. Tour, Growth of graphene from food, insects, and waste, ACS Nano 5 (2011) 7601–7607. [27] X.-H. Li, S. Kurasch, U. Kaiser, M. Antonietti, Synthesis of monolayer-patched graphene from glucose, Angew. Chem. Int. Ed. 51 (2012) 9689–9692. [28] J. Qu, C. Luo, Q. Zhang, Q. Cong, X. Yuan, Easy synthesis of graphene sheets from alfalfa plants by treatment of nitric acid, Mater. Sci. Eng. B Adv. Funct. Solid State Mater. 178 (2013) 380–382. [29] S.S. Gupta, T.S. Sreeprasad, S.M. Maliyekkal, S.K. Das, T. Pradeep, Graphene from sugar and its application in water purification, ACS Appl. Mater. Interfaces 4 (2012) 4156–4163. [30] G. Kalita, S. Sharma, K. Wakita, M. Umeno, Y. Hayashi, M. Tanemura, Synthesis of graphene by surface wave plasma chemical vapor deposition from camphor, Phys. Status Solidi A Appl. Mater. 209 (2012) 2510–2513. [31] N.R. Yaffe, E.W. Blanch, Effects and anomalies that can occur in SERS spectra of biological molecules when using a wide range of aggregating agents for hydroxylamine-reduced and citrate-reduced silver colloids, Vib. Spectrosc. 48 (2008) 196–201. [32] L. Gunnarsson, S. Petronis, B. Kasemo, H. Xu, J. Bjerneld, M. Käll, Optimizing nanofabricated substrates for surface enhanced Raman scattering, Nanostruct. Mater. 12 (1999) 783–788.

A.K. Sundramoorthy, S. Gunasekaran/Trends in Analytical Chemistry 60 (2014) 36–53

[33] F. Schedin, E. Lidorikis, A. Lombardo, V.G. Kravets, A.K. Geim, A.N. Grigorenko, K.S. Novoselov, A.C. Ferrari, Surface-enhanced Raman spectroscopy of graphene, ACS Nano 4 (2010) 5617–5626. [34] J. Liu, H. Cai, X. Yu, K. Zhang, X. Li, J. Li, N. Pan, Q. Shi, Y. Luo, X. Wang, Fabrication of graphene nanomesh and improved chemical enhancement for raman spectroscopy, J. Phys. Chem. C 116 (2012) 15741–15746. [35] J. Fan, Z. Shi, Y. Ge, J. Wang, Y. Wang, J. Yin, Gum arabic assisted exfoliation and fabrication of Ag-graphene-based hybrids, J. Mater. Chem. 22 (2012) 13764–13772. [36] Y. Xie, Y. Li, L. Niu, H. Wang, H. Qian, W. Yao, A novel surface-enhanced Raman scattering sensor to detect prohibited colorants in food by graphene/silver nanocomposite, Talanta 100 (2012) 32–37. [37] S.J. Lee, A.R. Morrill, M. Moskovits, Hot spots in silver nanowire bundles for surface-enhanced Raman spectroscopy, J. Am. Chem. Soc. 128 (2006) 2200– 2201. [38] S.E. Hunyadi, C.J. Murphy, Bimetallic silver-gold nanowires: fabrication and use in surface-enhanced Raman scattering, J. Mater. Chem. 16 (2006) 3929– 3935. [39] L.K. Massey, H. Roman-Smith, R.A.L. Sutton, Effect of dietary oxalate and calcium on urinary oxalate and risk of formation of calcium oxalate kidney stones, J. Am. Diet. Assoc. 93 (1993) 901–906. [40] T.A. Ivandini, T.N. Rao, A. Fujishima, Y. Einaga, Electrochemical oxidation of oxalic acid at highly boron-doped diamond electrodes, Anal. Chem. 78 (2006) 3467–3471. [41] X. Chen, Z. Cai, Z. Huang, M. Oyama, Y. Jiang, X. Chan, Non-enzymatic oxalic acid sensor using platinum nanoparticles modified on graphene nanosheets, Nanoscale 5 (2013) 5779–5783. [42] T.J. Preston, W.J. Muller, G. Singh, Scavenging of extracellular H2O2 by catalase inhibits the proliferation of HER-2/Neu-transformed rat-1 fibroblasts through the induction of a stress response, J. Biol. Chem. 276 (2001) 9558–9564. [43] X. Chen, X.-M. Chen, Z.-X. Cai, Z.-Y. Huang, M. Oyama, Y.-Q. Jiang, Ultrafine palladium nanoparticles grown on graphene nanosheets for enhanced electrochemical sensing of hydrogen peroxide, Electrochim. Acta 97 (2013) 398–403. [44] K.S. Rowe, K.J. Rowe, Synthetic food coloring and behavior: a dose response effect in a double-blind, placebo-controlled, repeated-measures study, J. Pediatr. 125 (1994) 691–698. [45] D.D. Stevenson, R.A. Simon, W.R. Lumry, D.A. Mathison, Adverse reactions to tartrazine, J. Allergy Clin. Immunol. 78 (1986) 182–191. [46] S.P. Alves, D.M. Brum, É.C. Branco de Andrade, A.D. Pereira Netto, Determination of synthetic dyes in selected foodstuffs by high performance liquid chromatography with UV-DAD detection, Food Chem. 107 (2008) 489–496. [47] T. Gan, J. Sun, S. Cao, F. Gao, Y. Zhang, Y. Yang, One-step electrochemical approach for the preparation of graphene wrapped-phosphotungstic acid hybrid and its application for simultaneous determination of sunset yellow and tartrazine, Electrochim. Acta 74 (2012) 151–157. [48] T. Gan, J. Sun, M. He, L. Wang, Highly sensitive electrochemical sensor for Sudan I based on graphene decorated with mesoporous TiO2, Ionics (2013) 1–7. [49] T. Gan, J. Sun, Z. Lin, Y. Li, Highly sensitive determination of Orange II based on the dual amplified electrochemical signal of graphene and mesoporous TiO2, Anal. Methods 5 (2013) 2964–2970. [50] T. Gan, J. Sun, W. Meng, L. Song, Y. Zhang, Electrochemical sensor based on graphene and mesoporous TiO2 for the simultaneous determination of trace colourants in food, Food Chem. 141 (2013) 3731–3737. [51] W.B. Guan, Z.N. Li, H.Y. Zhang, H.J. Hong, N. Rebeyev, Y. Ye, Y.Q. Ma, Amine modified graphene as reversed-dispersive solid phase extraction materials combined with liquid chromatography-tandem mass spectrometry for pesticide multi-residue analysis in oil crops, J. Chromatogr. A 1286 (2013) 1–8. [52] Z. Li, M.Y. Hou, S.S. Bai, C. Wang, Z. Wang, Extraction of imide fungicides in water and juice samples using magnetic graphene nanoparticles as adsorbent followed by their determination with gas chromatography and electron capture detection, Anal. Sci. 29 (2013) 325–331. [53] V.K. Ponnusamy, J.F. Jen, A novel graphene nanosheets coated stainless steel fiber for microwave assisted headspace solid phase microextraction of organochlorine pesticides in aqueous samples followed by gas chromatography with electron capture detection, J. Chromatogr. A 1218 (2011) 6861–6868. [54] G.Y. Zhao, S.J. Song, C. Wang, Q.H. Wu, Z. Wang, Solid-phase microextraction with a novel graphene-coated fiber coupled with high-performance liquid chromatography for the determination of some carbamates in water samples, Anal. Methods 3 (2011) 2929–2935. [55] G.Y. Zhao, S.J. Song, C. Wang, Q.H. Wu, Z. Wang, Determination of triazine herbicides in environmental water samples by high-performance liquid chromatography using graphene-coated magnetic nanoparticles as adsorbent, Anal. Chim. Acta 708 (2011) 155–159. [56] H. Zhang, H.K. Lee, Simultaneous determination of ultraviolet filters in aqueous samples by plunger-in-needle solid-phase microextraction with graphenebased sol-gel coating as sorbent coupled with gas chromatography-mass spectrometry, Anal. Chim. Acta 742 (2012) 67–73. [57] L. Yu, P.W. Li, Q. Zhang, W. Zhang, X.X. Ding, X.P. Wang, Graphene oxide: an adsorbent for the extraction and quantification of aflatoxins in peanuts by high-performance liquid chromatography, J. Chromatogr. A 1318 (2013) 27–34. [58] M.M. Tian, W. Feng, J.J. Ye, Q. Jia, Preparation of Fe3O4@TiO2/graphene oxide magnetic microspheres for microchip-based preconcentration of estrogens in milk and milk powder samples, Anal. Methods 5 (2013) 3984–3991. [59] Z.H. Wang, H. Cui, J.F. Xia, Q. Han, N.N. Lv, J.G. Gao, X.M. Guo, F.F. Zhang, J.M. Ma, G.K. Su, A novel method for bisphenol A analysis in dairy products using

[60]

[61]

[62]

[63]

[64]

[65]

[66]

[67]

[68]

[69]

[70]

[71]

[72]

[73]

[74]

[75]

[76]

[77]

[78]

[79]

[80]

[81]

[82] [83]

[84]

51

graphene as an adsorbent for solid phase extraction followed by ion chromatography, Food Anal. Methods 6 (2013) 1537–1543. J.B. Wu, Y.S. Qian, C.L. Zhang, T.L. Zheng, L.Y. Chen, Y.B. Lu, H.Z. Wang, Application of graphene-based solid-phase extraction coupled with ultra high-performance liquid chromatography-tandem mass spectrometry for determination of macrolides in fish tissues, Food Anal. Methods 6 (2013) 1448–1457. L.L. Xu, J.J. Feng, J.B. Li, X. Liu, S.X. Jiang, Graphene oxide bonded fused-silica fiber for solid-phase microextraction-gas chromatography of polycyclic aromatic hydrocarbons in water, J. Sep. Sci. 35 (2012) 93–100. J. Hou, F. Bei, M. Wang, S. Ai, Electrochemical determination of malachite green at graphene quantum dots–gold nanoparticles multilayers–modified glassy carbon electrode, J. Appl. Electrochem. 43 (2013) 689–696. M.-Y. Hua, H.-C. Chen, R.-Y. Tsai, Y.-L. Leu, Y.-C. Liu, J.-T. Lai, Synthesis and characterization of carboxylated polybenzimidazole and its use as a highly sensitive and selective enzyme-free H2O2 sensor, J. Mater. Chem. 21 (2011) 7254–7262. H.N. Lim, R. Nurzulaikha, I. Harrison, S.S. Lim, W.T. Tan, M.C. Yeo, M.A. Yarmo, N.M. Huang, Preparation and characterization of tin oxide, SnO2 nanoparticles decorated graphene, Ceram. Int. 38 (2012) 4209–4216. J.-J. Liu, X.-L. Zhang, Z.-X. Cong, Z.-T. Chen, H.-H. Yang, G.-N. Chen, Glutathionefunctionalized graphene quantum dots as selective fluorescent probes for phosphate-containing metabolites, Nanoscale 5 (2013) 1810–1815. A.-X. Zheng, Z.-X. Cong, J.-R. Wang, J. Li, H.-H. Yang, G.-N. Chen, Highly-efficient peroxidase-like catalytic activity of graphene dots for biosensing, Biosens. Bioelectron. 49 (2013) 519–524. Y. Song, K. Qu, C. Zhao, J. Ren, X. Qu, Graphene oxide: intrinsic peroxidase catalytic activity and its application to glucose detection, Adv. Mater. 22 (2010) 2206–2210. J. Jiang, W. Fan, X. Du, Nitrite electrochemical biosensing based on coupled graphene and gold nanoparticles, Biosens. Bioelectron. 51 (2014) 343–348. M. Karimi, F. Aboufazeli, H. Zhad, O. Sadeghi, E. Najafi, Cadmium ions determination in sea food samples using dipyridyl-functionalized graphene nano-sheet, Food Anal. Methods (2013) 1–7. X. Lin, Y. Ni, S. Kokot, Voltammetric analysis with the use of a novel electropolymerised graphene-nafion film modified glassy carbon electrode: simultaneous analysis of noxious nitroaniline isomers, J. Hazard. Mater. 243 (2012) 232–241. J. Luo, Y. Chen, Q. Ma, R. Liu, X. Liu, Layer-by-layer self-assembled hybrid multilayer films based on poly(sodium 4-styrenesulfonate) stabilized graphene with polyaniline and their electrochemical sensing properties, RSC Adv. 3 (2013) 17866–17873. X. Ma, M. Chao, Z. Wang, Electrochemical determination of Sudan I in food samples at graphene modified glassy carbon electrode based on the enhancement effect of sodium dodecyl sulphonate, Food Chem. 138 (2013) 739–744. P. Si, X.-C. Dong, P. Chen, D.-H. Kim, A hierarchically structured composite of Mn3O4/3 D graphene foam for flexible nonenzymatic biosensors, J. Mater. Chem. B 1 (2013) 110–115. H. Song, Y. Ni, S. Kokot, A novel electrochemical biosensor based on the hemin-graphene nano-sheets and gold nano-particles hybrid film for the analysis of hydrogen peroxide, Anal. Chim. Acta 788 (2013) 24–31. H. Wang, Y. Zhang, H. Li, B. Du, H. Ma, D. Wu, Q. Wei, A silver-palladium alloy nanoparticle-based electrochemical biosensor for simultaneous detection of ractopamine, clenbuterol and salbutamol, Biosens. Bioelectron. 49 (2013) 14–19. H. Xu, H. Dai, G. Chen, Direct electrochemistry and electrocatalysis of hemoglobin protein entrapped in graphene and chitosan composite film, Talanta 81 (2010) 334–338. X. Ye, Y. Du, D. Lu, C. Wang, Fabrication of -cyclodextrin-coated poly (diallyldimethylammonium chloride)-functionalized graphene composite film modified glassy carbon-rotating disk electrode and its application for simultaneous electrochemical determination colorants of sunset yellow and tartrazine, Anal. Chim. Acta 779 (2013) 22–34. S. Cao, L. Zhang, Y. Chai, R. Yuan, An integrated sensing system for detection of cholesterol based on TiO2-graphene-Pt-Pd hybrid nanocomposites, Biosens. Bioelectron. 42 (2013) 532–538. M.C. Tonon, D. Lanfray, H. Castel, H. Vaudry, F. Morin, Hypothalamic glucosesensing: role of glia-to-neuron signaling, Horm. Metab. Res. 45 (2013) 955– 959. X. Cao, Y. Ye, Y. Li, X. Xu, J. Yu, S. Liu, Self-assembled glucose oxidase/graphene/ gold ternary nanocomposites for direct electrochemistry and electrocatalysis, J. Electroanal. Chem. 697 (2013) 10–14. H. Chen, B. Zhang, Y. Cui, B. Liu, G. Chen, D. Tang, One-step electrochemical immunoassay of biomarker based on nanogold-functionalized graphene sensing platform, Anal. Methods 3 (2011) 1615–1621. A. Høst, Frequency of cow’s milk allergy in childhood, Ann. Allergy Asthma Immunol. 89 (2002) 33–37. S. Eissa, C. Tlili, L. L’Hocine, M. Zourob, Electrochemical immunosensor for the milk allergen β-lactoglobulin based on electrografting of organic film on graphene modified screen-printed carbon electrodes, Biosens. Bioelectron. 38 (2012) 308–313. H. Chen, Z. Gao, Y. Cui, G. Chen, D. Tang, Nanogold-enhanced graphene nanosheets as multienzyme assembly for sensitive detection of lowabundanceproteins, Biosens. Bioelectron. 44 (2013) 108–114.

52

A.K. Sundramoorthy, S. Gunasekaran/Trends in Analytical Chemistry 60 (2014) 36–53

[85] H. Chen, D. Tang, B. Zhang, B. Liu, Y. Cui, G. Chen, Electrochemical immunosensor for carcinoembryonic antigen based on nanosilver-coated magnetic beads and gold-graphene nanolabels, Talanta 91 (2012) 95–102. [86] C.-H. Lu, J. Li, M.-H. Lin, Y.-W. Wang, H.-H. Yang, X. Chen, G.-N. Chen, Amplified aptamer-based assay through catalytic recycling of the analyte, Angew. Chem. Int. Ed. 49 (2010) 8454–8457. [87] C.-H. Lu, J. Li, J.-J. Liu, H.-H. Yang, X. Chen, G.-N. Chen, Increasing the sensitivity and single-base mismatch selectivity of the molecular beacon using graphene oxide as the “nanoquencher”, Chem. Eur. J. 16 (2010) 4889–4894. [88] L. Hou, Y. Cui, M. Xu, Z. Gao, J. Huang, D. Tang, Graphene oxide-labeled sandwich-type impedimetric immunoassay with sensitive enhancement based on enzymatic 4-chloro-1-naphthol oxidation, Biosens. Bioelectron. 47 (2013) 149–156. [89] C.-H. Lu, J. Li, X.-J. Qi, X.-R. Song, H.-H. Yang, X. Chen, G.-N. Chen, Multiplex detection of nucleases by a graphene-based platform, J. Mater. Chem. 21 (2011) 10915–10919. [90] J. Luo, S. Jiang, X. Liu, Efficient one-pot synthesis of mussel-inspired molecularly imprinted polymer coated graphene for protein-specific recognition and fast separation, J. Phys. Chem. C 117 (2013) 18448–18456. [91] S. He, B. Song, D. Li, C. Zhu, W. Qi, Y. Wen, L. Wang, S. Song, H. Fang, C. Fan, A graphene nanoprobe for rapid, sensitive, and multicolor fluorescent DNA analysis, Adv. Funct. Mater. 20 (2010) 453–459. [92] W. Wei, D.M. Zhang, L.H. Yin, Y.P. Pu, S.Q. Liu, Colorimetric detection of DNA damage by using hemin-graphene nanocomposites, Spectrochim. Acta A Mol. Biomol. Spectrosc. 106 (2013) 163–169. [93] J. Wu, Q. Liu, K. Wang, J. Cai, Enhanced Direct Electrochemistry of Glucose Oxidase and Glucose Biosensing Based on TiO2 – Decorated Graphene Nanohybrids, Trans Tech Publications, Zhengzhou, 2012, pp. 507–510. [94] X. Dominguez-Benetton, S. Sevda, K. Vanbroekhoven, D. Pant, The accurate use of impedance analysis for the study of microbial electrochemical systems, Chem. Soc. Rev. 41 (2012) 7228–7246. [95] A.M. Attaran, M. Javanbakht, F. Fathollahi, M. Enhessari, Determination of salbutamol in pharmaceutical and serum samples by adsorptive stripping voltammetry on a carbon paste electrode modified by iron titanate nanopowders, Electroanalysis 24 (2012) 2013–2020. [96] M. Rajkumar, Y.-S. Li, S.-M. Chen, Electrochemical detection of toxic ractopamine and salbutamol in pig meat and human urine samples by using poly taurine/zirconia nanoparticles modified electrodes, Colloids Surf. B Biointerfaces 110 (2013) 242–247. [97] J. Huang, Q. Lin, X. Zhang, X. He, X. Xing, W. Lian, M. Zuo, Q. Zhang, Electrochemical immunosensor based on polyaniline/poly (acrylic acid) and Au-hybrid graphene nanocomposite for sensitivity enhanced detection of salbutamol, Food Res. Int. 44 (2011) 92–97. [98] F. Schedel, R. Pries, B. Thode, B. Wollmann, S. Wulff, D. Jocham, B. Wollenberg, I. Kausch, mTOR inhibitors show promising in vitro activity in bladder cancer and head and neck squamous cell carcinoma, Oncol. Rep. 25 (2011) 763–768. [99] Q. Li, D. Tang, J. Tang, B. Su, G. Chen, M. Wei, Magneto-controlled electrochemical immunosensor for direct detection of squamous cell carcinoma antigen by using serum as supporting electrolyte, Biosens. Bioelectron. 27 (2011) 153–159. [100] J. Ping, Y. Wang, K. Fan, W. Tang, J. Wu, Y. Ying, High-performance flexible potentiometric sensing devices using free-standing graphene paper, J. Mater. Chem. B 1 (2013) 4781–4791. [101] C. Tyler, E. Routledge, Oestrogenic effects in fish in English rivers with evidence of their causation, Pure Appl. Chem. 70 (1998) 1795- 1804. [102] L.B. Christensen, M. Winther-Nielsen, C. Helweg, Feminisation of Fish – the Effect of Estrogenic Compounds and Their Fate in Sewage Treatment Plant and Nature. Environmental Project no. 729, Danish Environmental Protection Agency, 2002. [103] E. Pretsch, The new wave of ion-selective electrodes, Trac Trends Anal. Chem. 26 (2007) 46–51. [104] J. Ping, Y. Wang, Y. Ying, J. Wu, Application of electrochemically reduced graphene oxide on screen-printed ion-selective electrode, Anal. Chem. 84 (2012) 3473–3479. [105] F. Valentini, M. Carbone, G. Palleschi, Graphene oxide nanoribbons (GNO), reduced graphene nanoribbons (GNR), and multi-layers of oxidized graphene functionalized with ionic liquids (GO-IL) for assembly of miniaturized electrochemical devices, Anal. Bioanal. Chem. 405 (2013) 3449–3474. [106] T.T. Tung, M. Castro, T.Y. Kim, K.S. Suh, J.-F. Feller, Graphene quantum resistive sensing skin for the detection of alteration biomarkers, J. Mater. Chem. 22 (2012) 21754–21766. [107] B. Kumar, M. Castro, J.F. Feller, Poly(lactic acid)–multi-wall carbon nanotube conductive biopolymer nanocomposite vapour sensors, Sens. Actuators B Chem. 161 (2012) 621–628. [108] P. Bhattacharjee, S. Panigrahi, D. Lin, C. Logue, J. Sherwood, C. Doetkott, M. Marchello, A comparative qualitative study of the profile of volatile organic compounds associated with Salmonella contamination of packaged aged and fresh beef by HS-SPME/GC-MS, J. Food Sci. Technol. 48 (2011) 1–13. [109] M. Peris, L. Escuder-Gilabert, A 21st century technique for food control: electronic noses, Anal. Chim. Acta 638 (2009) 1–15. [110] Y. Xu, S. Barringer, Comparison of tomatillo and tomato volatile compounds in the headspace by selected ion flow tube mass spectrometry (SIFT-MS), J. Food Sci. 75 (2010) C268-C273. [111] J. Regueiro, A.E. Rossignoli, G. Álvarez, J. Blanco, Automated on-line solid-phase extraction coupled to liquid chromatography–tandem mass spectrometry for

[112]

[113]

[114]

[115] [116]

[117]

[118]

[119]

[120]

[121]

[122]

[123]

[124]

[125]

[126]

[127]

[128]

[129]

[130]

[131]

[132]

[133]

[134]

[135] [136]

[137]

determination of lipophilic marine toxins in shellfish, Food Chem. 129 (2011) 533–540. M. Campas, D. Garibo, B. Prieto-Simon, Novel nanobiotechnological concepts in electrochemical biosensors for the analysis of toxins, Analyst 137 (2012) 1055–1067. J.C. Vidal, L. Bonel, A. Ezquerra, S. Hernandez, J.R. Bertolin, C. Cubel, J.R. Castillo, Electrochemical affinity biosensors for detection of mycotoxins: a review, Biosens. Bioelectron. 49 (2013) 146–158. Q. Shen, L. Gong, J.T. Baibado, W. Dong, Y. Wang, Z. Dai, H.-Y. Cheung, Graphene based pipette tip solid phase extraction of marine toxins in shellfish muscle followed by UPLC-MS/MS analysis, Talanta 116 (2013) 770–775. S. Marin, A.J. Ramos, G. Cano-Sancho, V. Sanchis, Mycotoxins: occurrence, toxicology, and exposure assessment, Food Chem. Toxicol. 60 (2013) 218–237. S. Wu, N. Duan, X. Ma, Y. Xia, H. Wang, Z. Wang, Q. Zhang, Multiplexed fluorescence resonance energy transfer aptasensor between upconversion nanoparticles and graphene oxide for the simultaneous determination of mycotoxins, Anal. Chem. 84 (2012) 6263–6270. D. Tang, B. Zhang, J. Tang, L. Hou, G. Chen, Displacement-type quartz crystal microbalance immunosensing platform for ultrasensitive monitoring of small molecular toxins, Anal. Chem. 85 (2013) 6958–6966. J. Tang, L. Hou, D. Tang, J. Zhou, Z. Wang, J. Li, G. Chen, Magneto-controlled electrochemical immunoassay of brevetoxin B in seafood based on guaninefunctionalized graphene nanoribbons, Biosens. Bioelectron. 38 (2012) 86–93. J. Li, J. Chen, X.-L. Zhang, C.-H. Lu, H.-H. Yang, A novel sensitive detection platform for antitumor herbal drug aloe-emodin based on the graphene modified electrode, Talanta 83 (2010) 553–558. X. Lin, Y. Ni, S. Kokot, A novel electrochemical sensor for the analysis of -agonists: the poly(acid chrome blue K)/graphene oxide-nafion/glassy carbon electrode, J. Hazard. Mater. 260 (2013) 508–517. Q. Liu, Y. Yan, X. Yang, J. Qian, J. Cai, K. Wang, Fe3O4-functionalized graphene nanoribbons: preparation, characterization, and improved electrochemical activity, J. Electroanal. Chem. 704 (2013) 86–89. J. Yang, J.R. Strickler, S. Gunasekaran, Indium tin oxide-coated glass modified with reduced graphene oxide sheets and gold nanoparticles as disposable working electrodes for dopamine sensing in meat samples, Nanoscale 4 (2012) 4594–4602. P. Lu, S. Liu, G. Dai, Y. Lei, Y. Liang, Enhancement in detection of glucose based on a nickel hexacyanoferrate- reduced graphene oxide-modified glassy carbon electrode, Aust. J. Chem. 66 (2013) 983–988. J. Yang, J.H. Yu, J.R. Strickler, W.J. Chang, S. Gunasekaran, Nickel nanoparticlechitosan-reduced graphene oxide-modified screen-printed electrodes for enzyme-free glucose sensing in portable microfluidic devices, Biosens. Bioelectron. 47 (2013) 530–538. J. Tang, D. Tang, Q. Li, B. Su, B. Qiu, G. Chen, Sensitive electrochemical immunoassay of carcinoembryonic antigen with signal dual-amplification using glucose oxidase and an artificial catalase, Anal. Chim. Acta 697 (2011) 16–22. Q. Wei, Y. Zhao, B. Du, D. Wu, H. Li, M. Yang, Ultrasensitive detection of kanamycin in animal derived foods by label-free electrochemical immunosensor, Food Chem. 134 (2012) 1601–1606. C. Wu, D. Sun, Q. Li, K. Wu, Electrochemical sensor for toxic ractopamine and clenbuterol based on the enhancement effect of graphene oxide, Sens. Actuators B Chem. 168 (2012) 178–184. J. Yang, S. Deng, J. Lei, H. Ju, S. Gunasekaran, Electrochemical synthesis of reduced graphene sheet-AuPd alloy nanoparticle composites for enzymatic biosensing, Biosens. Bioelectron. 29 (2011) 159–166. B. Zhang, D. Tang, B. Liu, Y. Cui, H. Chen, G. Chen, Nanogold-functionalized magnetic beads with redox activity for sensitive electrochemical immunoassay of thyroid-stimulating hormone, Anal. Chim. Acta 711 (2012) 17–23. B. Zhang, D. Tang, B. Liu, H. Chen, Y. Cui, G. Chen, GoldMag nanocompositefunctionalized graphene sensing platform for one-step electrochemical immunoassay of alpha-fetoprotein, Biosens. Bioelectron. 28 (2011) 174–180. B.Y. Zhao, Q. Wei, C. Xu, H. Li, D. Wu, Y. Cai, K. Mao, Z. Cui, B. Du, Label-free electrochemical immunosensor for sensitive detection of kanamycin, Sens. Actuators B Chem. 155 (2011) 618–625. J. Zhou, J. Zhuang, M. Miro, Z. Gao, G. Chen, D. Tang, Carbon nanospherespromoted electrochemical immunoassay coupled with hollow platinum nanolabels for sensitivity enhancement, Biosens. Bioelectron. 35 (2012) 394–400. J. Zhou, D. Tang, L. Hou, Y. Cui, H. Chen, G. Chen, Nanoplatinum-enclosed gold nanocores as catalytically promoted nanolabels for sensitive electrochemical immunoassay, Anal. Chim. Acta 751 (2012) 52–58. M. Tankiewicz, J. Fenik, M. Biziuk, Determination of organophosphorus and organonitrogen pesticides in water samples, Trac Trend Anal. Chem. 29 (2010) 1050–1063. E. Council, Directive 98/83/EC on the quality of water intended for human consumption, Off. J. Eur. Commun. L 330 (1998) 32–54. L. Wang, X. Zang, Q. Chang, G. Zhang, C. Wang, Z. Wang, Determination of triazole fungicides in vegetable samples by magnetic solid-phase extraction with graphene-coated magnetic nanocomposite as adsorbent followed by gas chromatography–mass spectrometry detection, Food Anal. Methods (2013) 1–8. U. Koesukwiwat, S.J. Lehotay, K. Mastovska, K.J. Dorweiler, N. Leepipatpiboon, Extension of the QuEChERS method for pesticide residues in cereals to flaxseeds, peanuts, and doughs, J. Agric. Food. Chem. 58 (2010) 5950–5958.

A.K. Sundramoorthy, S. Gunasekaran/Trends in Analytical Chemistry 60 (2014) 36–53

[138] J. Chen, J. Zou, J. Zeng, X. Song, J. Ji, Y. Wang, J. Ha, X. Chen, Preparation and evaluation of graphene-coated solid-phase microextraction fiber, Anal. Chim. Acta 678 (2010) 44–49. [139] J.Y. Tian, J.Q. Xu, F. Zhu, T.B. Lu, C.Y. Su, G.F. Ouyang, Application of nanomaterials in sample preparation, J. Chromatogr. A 1300 (2013) 2–16. [140] B.-T. Zhang, X. Zheng, H.-F. Li, J.-M. Lin, Application of carbon-based nanomaterials in sample preparation: a review, Anal. Chim. Acta 784 (2013) 1–17. [141] O. Akhavan, E. Ghaderi, Toxicity of graphene and graphene oxide nanowalls against bacteria, ACS Nano 4 (2010) 5731–5736. [142] W.-P. Xu, L.-C. Zhang, J.-P. Li, Y. Lu, H.-H. Li, Y.-N. Ma, W.-D. Wang, S.-H. Yu, Facile synthesis of silver@graphene oxide nanocomposites and their enhanced antibacterial properties, J. Mater. Chem. 21 (2011) 4593–4597. [143] W. Hu, C. Peng, W. Luo, M. Lv, X. Li, D. Li, Q. Huang, C. Fan, Graphene-based antibacterial paper, ACS Nano 4 (2010) 4317–4323.

53

[144] Y.-W. Wang, Y.-Y. Fu, L.-J. Wu, J. Li, H.-H. Yang, G.-N. Chen, Targeted photothermal ablation of pathogenic bacterium, Staphylococcus aureus, with nanoscale reduced graphene oxide, J. Mater. Chem. B 1 (2013) 2496– 2501. [145] S.W. Chook, C.H. Chia, S. Zakaria, M.K. Ayob, K.L. Chee, N.M. Huang, H.M. Neoh, H.N. Lim, R. Jamal, R.M.F.R.A. Rahman, Antibacterial performance of Ag nanoparticles and AgGO nanocomposites prepared via rapid microwaveassisted synthesis method, Nanoscale Res. Lett. 7 (2012) 1–7. [146] S.K. Yadav, Y.C. Jung, J.H. Kim, Y.-I. Ko, H.J. Ryu, M.K. Yadav, Y.A. Kim, J.W. Cho, Mechanically robust, electrically conductive biocomposite films using antimicrobial chitosan-functionalized graphenes, Part. Part. Syst. Charact. 30 (2013) 721–727. [147] H. Kim, A.A. Abdala, C.W. Macosko, Graphene/polymer nanocomposites, Macromolecules 43 (2010) 6515–6530.