graphene: the cutting–edge interaction between chemistry and electrochemistry

Trends in Analytical Chemistry 56 (2014) 13–26

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Review

Graphene: The cutting–edge interaction between chemistry andelectrochemistry

http://dx.doi.org/10.1016/j.trac.2013.12.0080165-9936/� 2014 Elsevier Ltd. All rights reserved.

Abbreviations: AA, Ascorbic acid; AFM, Atomic force microscopy; CA, Chronoamperometry; CC, Chronocoulometry; CT, Catechol; CV, Cyclic voltammetrChemically-modified graphene; CNT, Carbon nanotube; CTAB, Cetyl trimethylammonium bromide; CVD, Chemical-vapor deposition; 2-D, Two-dimensional; DA, DoDMF, Dimethylformamide; EPD, Electrophoretic deposition; FET, Field-emission transistor; FL, Few-layer; GCE, Glassy-carbon electrode; GNP, Graphene nanoplateGraphene nanoribbon; GNS, Graphene nanosheet; GO, Graphene oxide; GOx, Glucose oxidase; Hb, Hemoglobin; HET, Heterogeneous electron transfer; HOPG, Highly-pyrolytic graphite; HQ, Hydroquinone; HX, Hypoxanthine; ITO, Indium tin oxide; LD, Levodopa; LOD, Limit of detection; L-Tyr, L-Tyrosine; MLG, Multilayer gMWCNT, Multi-walled carbon nanotube; NMR, Nuclear magnetic resonance; NO, Nitric oxide; 4-NP, 4-Nitrophenol; 1-OHP, 1-Hydroxypyrene; PAH, Polycyclichydrocarbon; PEI, Polyethyleneimine; rGO, Reduced graphene oxide; RS, Resorcinol; SDBS, Sodium dodecyl benzyl sulfate; SDS, Sodium dodecyl sulfate; SEM,electron microscopy; SL, Single-layer; SPE, Screen-printed electrode; SWCNT, Single-walled carbon nanotube; TEM, Transmission electron microscopy; TGA, Thermetric analysis; TNT, 2,4,6-Trinitrotoluene; UA, Uric acid; XA, Xanthine; XPS, X-ray photoelectron spectroscopy; XRD, X-ray diffraction.⇑ Corresponding author. Fax: +34 91 885 49 71.

E-mail address: [email protected] (A. Escarpa).

Aida Martín, Alberto Escarpa ⇑Department of Analytical Chemistry, Physical Chemistry and Chemical Engineering, University of Alcalá, E-28871 Alcalá de Henares, Madrid, Spain

a r t i c l e i n f o

Keywords:CharacterizationChemical interactionElectrochemistryGrapheneGraphene nanoribbonGraphene oxideNanomaterialReduced graphene oxideSynthesisTarget molecule

a b s t r a c t

With the discovery of novel nanomaterials, electrochemistry is living a true Renaissance and graphene isits novel and central promise. This conceptual review includes a clear and straightforward scheme for ter-minology and properties, synthesis and characterization processes to obtain not only ‘‘true’’ graphene butalso some chemical variants, such as graphene oxide (GO), reduced graphene oxide (rGO) and graphenenanoribbons (GNR). Reviewing all these concepts, we explore the electrochemical applications of thesegraphenes, considering the chemical interaction between graphene and the target molecules explored.

� 2014 Elsevier Ltd. All rights reserved.

Contents

1. What does graphene stand for? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142. Graphene: synthesis and electrochemistry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153. Analytical characterization of graphene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154. Graphene chemistry behind the electrochemistry for sensing and biosensing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

4.1. Electrochemistry with GO. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
4.1.1. General context . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184.1.2. Electrochemical sensing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
4.2. Electrochemistry with rGO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
4.3. Electrochemistry with GNRs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
5. Outlook and perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

y; CMG,pamine;

let; GNR,orientedraphene;aromaticScanningmogravi-

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(a)

(b)

(c)

(d)

(e)

(f)

(i)

(j)

(k)

(l)

(m)

(n)

(o)

0-D 1-D 2-D 3-D

(h)

(g)

Fig. 1. Molecular models of sp2-bonded carbon nanostructures based on different dimensionalities: 0-D: (a) C60, Buckminsterfullerene, (b) nested giant fullerenes orgraphitic onions, (c) nanocones or nanohorns, (d) nanotoroids, (e) graphene clusters, (f) short carbon chains; 1-D: (g) carbon nanotubes (CNTs), (h) helicoidal CNTs; 2-D: (i)graphene surface, (j) Haeckelite surface, (k) nanoribbons 2D networks; 3-D: (l) 3D graphite crystal, (m) 3D Schwarzite crystals, (n) carbon nanofoams (interconnectedgraphene surfaces with channels), and (o) 3D CNT networks. {Modified with permission of [6]}.

14 A. Martín, A. Escarpa / Trends in Analytical Chemistry 56 (2014) 13–26

1. What does graphene stand for?

Recently, after Geim et al. achieved by a simple technique [1]the isolation of graphene sheets, this new nanomaterial attractedspecial interest in the scientific community. Graphene is a two-dimensional (2-D) sheet of carbon atoms bonded by sp2 bonds.This configuration provides this material with extraordinary prop-erties, such as large surface area, theoretically 2630 m2/g for a sin-gle layer [2], and double that of single-walled carbon nanotubes(SWCNTs). It also shows excellent thermal (k = 5 � 103 W m�1 K�1)[3] and electrical conductivity (r = 64 mS cm�1). Graphene is con-sidered a zero-gap semiconductor, because it presents no gap be-tween conduction and valance bands, so it might be considered a

SL-graphene FL-grap

Fig. 2. Graphene with a base size around hundred nm2:

semiconductor or a metal. In physical properties, graphene hasoptical transparence, high mechanical strength (Young’s modulus,�1100 GPa) [4] and high elasticity.

As shown in Fig. 1, in the multidimensional family of the carbonallotropes [5], the main examples are fullerenes as 0-D, SWCNTs 1-D and graphite 3-D. Eventually, graphene filled the second dimen-sion when the scientists awarded with the Nobel Physics Prize, ob-tained it from highly-oriented pyrolytic graphite (HOPG) by easyexfoliation techniques, and then characterized and isolated it [1].

In the ‘‘graphene’’ field, the terminology employed is important.In the References, we find many differences about graphene. First,according to the number of layers, three different groups areestablished:

hene ML-graphene

single-layer (SL), few-layer (FL) or multi-layer (ML).

Table 1Heterogeneous electron transfer (HET) rate for carbon materials based-electrodes. Values obtained from [12,13]

Carbon materials k0obs (cm s�1) Carbon materials k0

obs (cm s�1)

GCE 0.003 MWCNTs 2 � 10�5

Pyrolytic graphite 2–3 � 10�5 MWCNTs – 10% impurity 6 � 10�4

GO 5 � 10�5 MWCNTs – 30% impurity 2 � 10�3

rGO 4 � 10�4 to 0.005

A. Martín, A. Escarpa / Trends in Analytical Chemistry 56 (2014) 13–26 15

� a single layer;� a few layers (2–9); and,� multi-layer or graphite (more than 10 layers).

Fig. 2 illustrates this classification showing single-layer (SL),few-layer (FL) or multi-layer (ML) graphene structures [7].Although true graphene is only SL, the easy p–p interaction be-tween layers means that it is a real challenge to obtain one layer,in the synthesis process, and in the works published in theReferences.

Another classification is established considering the chemicalsynthesis of graphene, including the following terminologydepending on the carbon source.

When the carbon source is graphite, we could obtain chemi-cally-modified graphene (CMG), including graphene oxide (GO)or reduced graphene oxide (rGO).

If the carbon source comprises CNTs, graphene nanoribbons(GNRs) are synthesized after unzipping the CNTs.

Third, independent of the previous terminology, two moreterms are commonly employed in the literature

� graphene nanosheets (GNSs); and,� graphene nanoplatelets (GNPs), nanomaterials related to the

number of layers.

GNSs are the open equivalent to an SWCNT, which is one layerof graphene thick, and GNPs are, consequently, the open equivalentto the MWCNTs, which comprise a few layers.

All these terms are broadly used for graphene in the References.As a result, the reader must be critical with the material consid-ered. And above all, the reader should understand when we arereferring to graphite and when to graphene.

2. Graphene: synthesis and electrochemistry

Despite being a material with plenty of properties [8], just two –the large surface area and the high electrical conductivity are themost relevant properties for electrochemical applications.

Comparison between two of the most important carbon allo-tropes [i.e., SWCNTs (1-D) and graphene (2-D)], shows the follow-ing advantages for the 2-D material compared to 1-D [9].Compared with CNTs, graphene exhibits several advantages, suchas lower costs, larger surface area and easier processing. Moreover,graphene synthesized from graphite does not contain metallicimpurities and is cheaper because its carbon source is graphite [8].

In graphene, in contrast with CNTs, the large number of edgesper mass of the material permits higher heterogeneous electrontransfer (HET) rates [10,11]. Pumera et al. studied by cyclic voltam-metry the HET rate for different CMG materials with graphite andglassy-carbon electrodes (GCEs) as controls [12]. Furthermore, in aprevious work [13], Pumera et al. had also calculated the HET forMWCNTs and samples of MWCNTs with different content of nano-graphite impurities.

Table 1 summarizes the data obtained in both works. It indi-cates that reduced graphene material offers better electrochemicalperformance than graphite and MWCNTs and the data are close tothe data found for GCE. In other words, the electrochemical activity

of graphene is due to the presence of a higher density of sp2 do-mains and planes, and the higher number of plane edges that pres-ent defects. However, in CNTs, the electrochemical activity is alsodue to the presence of impurities from the synthesis process [14].

The improvement of graphene in the electron-transfer kinetics,as detailed below, facilitates the redox processes for molecules thatusually require high over-potentials to be oxidized or reduced.

Graphene has been synthesized by several methods, Geim et al.obtained it by the simple approach of peeling-off or ‘‘Scotch tape’’method, using a sticky tape and a pencil in 2004. However, the firstapproach of synthesis in 1979 [15] was chemical vapor deposition(CVD) and epitaxial growth on a nickel surface by the decomposi-tion of ethylene. In recent years, various methods for producingthis carbon allotrope have been developed, including epitaxialgrowth and chemical synthesis from graphite [16]. Table 2 summa-rizes the synthesis process and some electrochemical applicationsof those graphenes.

In electrochemical applications, mainly focusing on chemicalsensing and biosensing approaches, CMG is the main graphenesynthesized. In this synthesis route, the first step is oxidation ofthe graphite material, to obtain graphite oxide. This graphite oxideis exfoliated by physical methods, such as thermal shock or ultra-sonication to yield GO. Then, rGO is achieved by chemical, thermalor electrochemical reduction from the oxide sample. Although bothGO and rGO are widely used in electrochemistry for the detectionof different target molecules, rGO has demonstrated more advanta-ges for electrochemical applications. It is the structural defects andfunctional groups, as well as the large surface areas and electricalconductivities that permit the large number of electrochemicalapplications. Moreover, ‘‘unzipping’’ CNTs has permitted the syn-thesis of GNRs, which are, bit by bit, being used more inelectrochemistry.

Furthermore, new processes have been proposed to obtain GNSsusing both bottom-up and top-down strategies for synthesis.

3. Analytical characterization of graphene

After synthesis, the material needs to be characterized, andthere is a wide range of techniques [36–38], to obtain reliable,complete analytical information about the morphological, physicaland chemical structures. Table 3 summarizes the main techniquesinvolved in graphene characterization.

Microscopy techniques, such as scanning electron microscopy(SEM), transmission electron microscopy (TEM) and atomic forcemicroscopy (AFM), are required to evaluate morphological aspects.SEM images are mainly used to understand how the graphenematerial is deposited on different surfaces, chiefly onto electrodesurfaces [39]. Meanwhile, TEM permits an accurate morphologicaland topographical evaluation of graphene [12].

Information complementary to TEM is given by AFM. This is apowerful technique that plays a decisive role in graphene charac-terization because it estimates the number of layers [40,41]. A pris-tine single layer of graphene or ‘‘true graphene’’ is one layer thickwith a van der Waals thickness of�0.34 nm [1]. In GO, the compro-mise is that these sheets are expected to be thicker than pristinegraphene because of the presence of sp3-carbon atoms. Oxygenfunctionalities above and below the original plane suggest that

Table 2Terminology and synthesis for graphene for electroanalysis

Terminology Synthesis Route Synthesis conditions Target moleculea Remarks Ref.

Single layer ‘‘Peeling off’’ HOPG ND First isolation of one layer ofgraphene

[1]

Single layer Mechanical cleavage ND Large surface area. [17]Single-layer Intercalation of small

molecules in a graphite layerand exfoliation

Thermal shock Neurotransmitters Simple approach to obtainone layer. Possible structuraldefects

[18]Ultrasonication [19]

Single and few layers Epitaxial grown on silicon wafers ND Study of Dirac nature of thecharge carriers

[20]

Single and few layers CVD and epitaxial growth.Exposure of the metallicsurface to H2 and CH4 gases.Isolation of graphene

On single crystalline transitionmetal: Cu, Co, Pt, Ir, Ru and Ni

ND Bottom-up strategy. Metallicimpurities contained in thelayer

[21]

Few layers. CMG: GOand rGO.

Chemical treatment. [22]Oxidation of graphite toobtain graphite oxide, itsexfoliation yields (GO) andthe reduction of GO generates(rGO)

Oxidation Reduction Catecholamines,neurotransmitters, drugs,hydroquinone, H2O2, adenine,guanine, tryptophan,tyrosine, uric acid, ascorbicacid, glucose, TNT

Cheap synthesis. Lowmonolayer yields (1%).Structural defects. Smallsurface of layer. Introductionof heteroatomic impurities(from N2H4)

[22]Hummer andOfferman’smethod [23]

Chemicalreduction

Brodie’smethod [24]

Thermalreduction

Staudenmaier’smethod [25]

Electrochemicalreduction

Graphene nanoribbons(GNR)

‘‘Unzipping’’ of the CNTs Chemical oxidation of SWCNTs,opening up after treatment [26]

Catecholamines,neurotransmitters, NADH,H2O2, guanine, tyrosine,adenine, urea, glucose, TNT

Top-down strategy. Possiblepresence of unzipped CNTs

[6],[27]

Plasma etching, opening upMWCNTs [28]Lithium intercalation andexfoliation of MWCNTs [29]Nanoparticles of Ni are used asnano-knifes in a hydrogenatmosphere to act as catalytichydrogenation of carbon [30,31]Electrically unwrapping CNTs [32]Ionic liquid assisted splitting actionunder microwave radiation [33]

Graphene nanosheets(GNS)

Chemical reduction ofgraphite oxide byenvironmental friendlyagents: saccharides

Reduction with fructose, glucose,saccharose

Neurotransmitters:dopamine, adrenaline andnoradrenaline.

Green synthesis [34]

Graphene nanosheets(GNS)

Solvothermal synthesis usingethanol and sodium. Bypyrolysis of the NaOEtobtained

Bottom-up approach ND Common reagents. Low cost.Bulkquantities

[35]

a Detected at each graphene material. ND. Not detected.


one layer is �0.8 nm [42]. From the exceptional work thatpublished the discovery, Fig. 3 shows a single-sheet image usingAFM, and the presence of stacked layers because of p–pinteractions.

Raman, IR, nuclear magnetic resonance (NMR) and UV–Visspectroscopies have also been used in order to reveal the charac-teristics of the inner structure (defects and moieties in the sheet)[36]. Above all, Raman gives extraordinary analytical information,about the number of layers in the structure [38,43] and the innerstructure of graphene, as illustrated in Fig. 4.

While graphite exhibits a Raman spectrum with a typical G-band at 1590 cm�1, GO and rGO samples show differences in theirRaman spectra and display a G band at 1590 cm�1 and a D bandat 1360 cm�1. The G band corresponds to the carbon sp2 vibrationsof the domains in-plane, as in the graphite spectrum [44]. The Dband arises from the out-of-plane vibrational modes and is indica-tive of sp3 carbons present [45]. The intensity ratio of the D and Glines (ID/IG ratio) therefore provides important information becauseit is proportional to the average size of the sp2-carbon domain; as aresult, a decrease in the ratio ID/IG is attributed to the removal of de-fects [45]. However, in some cases, rGO can present a higher ID/IG

ratio than GO, and that would indicate that rGO presented manymore edges and would have been broken into more fragments [46].

IR spectra permit analysis of the functional moieties present inthe graphene samples and an estimation of the Csp2 and Csp3

content, comparing vibrations from graphitic domains. In general,the most probable bands are provoked by stretching and bendingvibrations from hydroxyl, epoxy or carboxyl groups [47]. WithrGO, the intensities of the bands associated with oxygen moietiesstrongly decrease compared to GO.

NMR is not a widely employed technique in graphene charac-terization, but, as with IR, it establishes the difference betweenrGO and GO. The 13C spectra are used to determine the presenceor the absence of oxygen groups; and wide bands are found inrGO due to the presence of different carbon-atom environmentsin the material [48].

UV-Vis spectroscopy mainly monitors the reaction reducing GOto rGO. GO displays an absorption peak at around 230 nm due tothe p–p⁄ transition of aromatic C@C bonds and a weak peak ataround 290 nm due to the n-p⁄ transition of the C@O bond. Asthe reaction yields rGO, the peak at 230 nm increases with thedecrease in intensity of the 290 nm band [36].

Furthermore, the moieties that are part of the graphene layercould be confirmed by X-ray photoelectron spectroscopy (XPS)and elemental analysis techniques. XPS of C 1s is a powerful toolto study the reduction of the oxygen content of the graphenefilms [36]. XPS can distinguish the groups of bonds and theoxidation state of carbons that are present in GO and rGO. GOpresents a complex spectrum due to the presence of oxide moie-ties, rGO mainly presents C–C and C@C bonds and its spectrum,

Table 3Analytical techniques used in graphene characterization

Technique Analytical information Analytical data for true graphene

Microscopy TEM Morphological Length layer Height of a layer�0.34 nmLength (100 nm�lm)

SEMAFM Number of layers

Spectroscopy Raman Inner structure Chemical groups and defects of the lattice Only sp2-carbonsIRUV-VisNMRXPS

X-Ray difraction XRD Structural Distances between layers �0.4 nm betweenlayers

Electrochemical techniques CV Inherent electrical properties HET rate Enhanced kinetics,Electrocatalysis andCurrent densities

CACCImpedance

A B

2.0nm 0.5 nm 0.8 nm

2.5 nm

1.2 nm

Fig. 3. AFM characterization of a single layer. (A) Graphene layer of �0.5 nm (in dark brown), few layers of �2 nm (in bright orange) and SiO2 surface (black). (B) Single layergraphene with thickness of two folds, approximately�0.8 nm. (C) Stacked graphene layers with height: 0.8 nm; 1.2 nm and 2.5 nm (in different red colors from dark to bright,the surface of SiO2 being dark brown at the background). {Reprinted with permission of [1]}.

Graphite

GO

rGO

GD

G

D

G

Fig. 4. Raman spectra of graphite, GO and rGO. {Modified with permission of [36]}.


centered at 285 eV, is simpler, because of its decrease in oxygengroups and the generation of large domains of p–conjugatedstructures [46].

Powder X-ray diffraction (XRD) can compare patterns of graph-ite and synthesized graphene and can measure the interlayer dis-tance between layers [49].

Additional techniques employed are thermal gravimetric analy-sis (TGA) to know the oxygen content of the graphene sample. Thismeasurement permits us to compare different graphene sampleswith different oxygen content. GO is thermally unstable and losesmass at 200�C because of pyrolysis of the labile oxygen moieties,and it yields CO, CO2 and water vapor [37].

The electrochemical behavior and electrochemical characteris-tics of graphene are evaluated using several techniques, such ascyclic voltammetry (CV), chronoamperometry (CA) or chronocoul-ometry (CC). Outer and inner sphere redox systems are commonlyscanned by electrochemical techniques to characterize the electro-chemical behavior of the graphene materials [50].

4. Graphene chemistry behind the electrochemistry for sensingand biosensing

Recently, we read one opinion that we firmly support – Electro-analysis is going through a true Renaissance due to the discovery ofnovel nanomaterials [51]. After the appearance of CNTs, whichevolved nanotechnology, graphene is the novelty in electroanalysis.Lots of target molecules of high significance in diverse fields areelectroactive, so their electrochemical detection has been en-hanced because nanomaterials offer excellent selectivity and sensi-tivity in direct detection without the need for any derivatizationstep.

The properties of graphene materials recently improved elec-trochemical sensing and biosensing [11,52–58]. As in other carbonand metallic nanomaterials, graphene has been used with three


ways: building thin-film and composite electrodes for sensing;and, electrochemical transducers for biosensing coupling with bio-molecules (enzymes, antibodies, DNA) for high selective and sensi-tive detection.

In the thin-film approach, the design of graphene-film elec-trodes is very simple. The underlying bulk electrode is modifiedwith graphene films, usually by the deposition of a suspension ofgraphenes in solvent {e.g., dimethylformamide (DMF) or other or-ganic solvent in the case of reduced graphene samples [59], waterin GO [37] and surfactant solutions in both cases [60]} and then thesolvent is evaporated. As a result, random graphene films are cre-ated on the surface of the electrodes.

In composite electrodes, graphene is mixed with other compo-nents or embedded in a polymer matrix. The main advantage ofthis design over graphene-film detectors is that graphene compos-ites are mechanically stable and significantly reduce noise levels.This is a classic characteristic of composite electrodes, which arecapable of acting as an array of microelectrodes or nanoelectrodeswith heavy overlapping diffusion zones. Thus, it provides signalsequivalent to macroelectrodes with the advantage of reducingnoise and a high signal-to-noise ratio. Furthermore, graphene eas-ily suffers from p–p stacking interactions, so the prevention ofaggregation, using polymers or other materials on graphene sur-faces, permits us to obtain individual sheets.

Finally, beyond chemical sensing, graphene has also been ex-plored in biosensing by using the same approach as that studiedwith several forms of carbon materials, such as graphite, carbonnanofibers or CNTs. Redox enzymes, such as glucose oxidase(GOx), or proteins are examples that usually integrate via assem-bling with a graphene surface.

4.1. Electrochemistry with GO

4.1.1. General contextGO includes a variety of reactive oxygen groups, such as

carboxyl (COOH), carbonyl (C@O), epoxide (–O–) and hydroxyl(–OH), linked to a network of C-sp3 structure. The precise chemicalstructure of GO has been an item of considerable discussion in re-cent years [22], the most accepted model published being by Lerfand Klinowski [61,62]. In this model (Fig. 5), alcohols and epoxidesform the basal plane, and carboxyl and carboxylic acid moieties arelocated at the edges. As discussed in the previous section on syn-thesis, this material may be obtained by thermal or mechanical

CHOCOOH

HOOC

OHC

COOH

O

OH

OH

Fig. 5. Graphe

exfoliation of graphite oxide through sonicating and/or stirring itin water [63], with the undesirable disadvantage of damaging theplatelets [38]. Furthermore, GO presents a negative charge whendispersed in water, suggesting that electrostatic repulsion betweennegatively-charged GO sheets could generate a stable aqueous sus-pension of them. Apart from that, it is also possible to functionalizeGO considering various chemical reactions that provide CMGs [22].These functionalizations involve in the reaction the carboxylic acidor epoxy groups that reduce the hydrophilic GO or the non-cova-lent functionalization of GO via p–p stacking, cation-p or van derWaals interactions on the sp2 system.

The main characteristic in the GO structure is the high percent-age of sp3 carbons as consequence of the oxidation treatment. Thiscauses a decrease of sp2 carbon content compared to rGO, whichprovokes aromatic loss in GO, and the consequent deficit in theHET rate (see Table 1). This structure of GO provides the specialfeatures of the material [64,65] and its use for many applications,as remarkable as polymer composites, energy-related materials,sensors, FETs and biomedical applications.

4.1.2. Electrochemical sensingWith selected examples, we critically examine the potential of

GO as an electrochemical transducer following the approachesabove (thin film, composite and biosensor-based electrodes) andremark on the chemical interaction with the molecules to bedetected.

With the thin-film approach, Chang et al. reported studies ofhow the voltammetric sensitivity and selectivity of detection ofuric acid (UA) and ascorbic acid (AA) at a screen-printed electrode(SPE) modified with nanoplatelets of graphitic oxide was im-proved. They used an original microwave-assisted hydrothermalelimination method [66] to explore the role of oxygen functional-ities and edge-plane sites on the electrochemical behavior of UAand AA. This method implied the generation of supercritical water,which acted as reducing agent under the solvothermal conditions,deoxygenating the oxygen moieties of the basal plane [67]. Ittherefore removed the oxygen-containing functional groups fromthe basal surface of the GO maintaining the edge-plane groups.By varying the temperature through microwave treatment, thereduction of the oxygen functional groups was controlled. Further-more; as the edge-plane-like sites were the electroactive sites; thisplatform retained the edge plane with tunable oxygen-containing

COOH

COOH

COOH

COOH

COOH

OH

O

O

OH

ne oxide.

Fig. 6. The proposed mechanism for the improved voltammetric detection of UA and AA at GO. {Reprinted with permission of [66]}.


functional groups and permitted in-depth comparison betweendifferent GO-modified electrodes and a non-modified SPE.

Surprisingly, meanwhile, using an SPE, AA and UA oxidized atthe same potential, a large shift in the oxidation potential of AAin cathodic direction was observed when using GO-modified elec-trodes and virtually the same peak potential was observed for UA.DE therefore shifted from 0 mV at the SPE to 19 mV, 58 mV and158 mV for GO with 6.3%, 7.7% and 9.9% in COOH moieties, respec-tively. UA did not show any electrocatalytic effect when a GO-mod-ified electrode was used. Fig. 6 shows the possible explanation whythis change in the oxidation potentials was found. This shift couldbe attributed to the very distinct ability of AA and UA to formhydrogen bonds with oxo-surface groups (especially the COOHgroup). The resulting potential shift observed for AA indicated thata direct chemical interaction between oxo-surface groups and AAwas involved in the reaction center during the oxidation step. ForUA, the hydrogen-bond interaction is far from the reaction center(lined in blue), so it does not interfere in the oxidation step.

A new 4-nitrophenol (4-NP) sensor was developed based on aGO film-coated GCE due to the special importance of the analysisof aromatic nitrocompounds in natural waters and effluents [68].The GO has strong adsorptive capability for 4-NP, because theyeasily interact by both hydrogen bonds and p–p stacking, as wellas by electrostatic interactions, since the nitrogen atom may bepositively charged. GO films therefore exhibited electrocatalyticactivity towards the reduction of 4-NP because they decreasedthe reduction overpotential to 54 mV and also showed good sensi-tivity, because the current in GO-modified electrode increased by afactor of four compared to GCE.

As covered, the chemical functionalization of graphene was alsoexplored in electrochemical applications. Carboxylic-acid-func-tionalized graphene (graphene-COOH) was prepared and used tomake a novel sensor for the simultaneous detection of adenineand guanine [69]. The negatively-charged graphene-COOH nano-film could interact with the positively-charged guanine and ade-nine analytes, and this effectively improved the sensitivity of theproposed method. As a result, with the modified electrode, thepeak currents increased nearly four times in contrast to the re-sponse of the bare GCE.

Two voltammetric sensors have been developed using GO-com-posite electrodes. In both cases, Nafion was the added materialmixed with GO. Important alkaloids, such as natural, everyday caf-feine [70] and colchicines [71], have been detected using a Nafion/GO/GCE sensor. Nafion increases the immobilization stability of GOon the electrode surface due to its ability to form excellent films,and, furthermore, Nafion may also interact with the positively-charged analytes, so permitting the adsorption of certain mole-cules, such as caffeine or colchicines, which are positively chargedat acid pH. Here, we suggest possible new routes to enhance thestability of films that would introduce positively-charged materialsinto the negatively-charged moieties of GO.

GO has also been explored in the design of biosensors. Whileusing GO, an increase in the signal and a significant change in po-tential detection have been achieved; the use of chitosan has alsoincreased the stability of GO on the GCE. The nanocomposite isbased on chitosan-ferrocene, graphene and GOx that catalyze theoxidation of glucose on a GCE [72]. Although GO has been usedin biosensing [73], the biological activity of the GO–enzyme conju-gate decreases when there is an electrostatic interaction betweenthe enzymes and the oxygen groups of GO [74]. For that reason,depending on the application, the most appropriate graphenewould be that which improves determination of the moleculebeing targeted.

4.2. Electrochemistry with rGO

4.2.1. General contextIt is usual to synthesize rGO by chemical, thermal or electro-

chemical reduction of GO or by other methods explained in theprevious sections and summarized in Table 2. The most commonroute for the synthesis of rGO is chemical, using compounds suchas hydrazine in ammonia (as shown in Fig. 7A). The chemical treat-ment provokes the reduction of epoxide groups, which are mainlylocated in the basal plane, whereas reductions of the hydroxyl, car-bonyl, and carboxyl groups are caused by thermal treatment dur-ing the reduction process [75]. Fig. 7B shows the rGO layer, inwhich a few oxygen groups remain in the sheet. The propertiesof this material are mainly explained by the general properties

A

HOOC

COOH

COOH

B

COOH

COOH

OH

OH

Fig. 7. (A) Reduction of epoxide group with hydrazine in NH3 media. (B) reduced graphene oxide. {Modified with permission of [75]}.


for one graphene sheet, but it may contain some oxygenated moi-eties that belonged to the GO sheet. As a result, the elemental anal-ysis of the rGOs measured by combustion revealed the existence ofa significant amount of oxygen (atomic C/O ratio, �10), indicatingthat rGO is not the same as a pristine graphene sheet. Theoreticalcalculations of rGO (the model used for GO with the graphenemodified with hydroxyl and epoxide groups) suggest that reduc-tion below 6.25% of the area of the GO (C/O = 16 in atomic ratio)may be difficult in terms of removing the remaining hydroxylgroups [3,76].

The main characteristic of rGO is the higher content of sp2-car-bon compared with GO. The natural consequence is the presence ofan enormous orbital p, which permits higher HET rates than GO(see Table 1). For this reason, it is the graphene most employedfor electrochemical sensing in the References.

Due to the strong tendency of graphene sheets to stack by p–pinteraction, the layers easily aggregate. However, this aggregationcould be overcome by the insertion of molecules that stabilizethe structure, dispersion in organic solvents or addition ofpolymers onto the nanosheets. Thus, the habitual solvents usedto disperse this material are mainly organic solvents, such asDMF, N,N0-dimethylacetamide, and N-methyl-2-pyrrolidone atconcentrations up to 1 mg mL�1 [37]. Despite being a veryhydrophobic molecule, graphene is also dispersed in water usingsurfactants, such as cetyl trimethylammonium bromide (CTAB),sodium dodecyl benzyl sulfate (SDBS) or sodium dodecyl sulfate(SDS) [77]. It is important that often the presence of somestabilizers is undesirable for most applications [78].

This unique nanostructure holds great promise for potentialapplications in many technological fields, such as nanoelectronics,sensors, capacitors, and nanocomposites [79–81].

4.2.2. Electrochemical sensingIn analytical and electrochemical applications, rGO is widely

used because of its excellent properties. Its chemical inertness, po-tential window and electrocatalytic activity in a variety of redoxreactions are the most prominent properties for its electrochemicalapplications. With the following selected examples, we criticallydiscuss the potential of rGO as an electrochemical transducer,focusing on the chemical interaction between graphene and themolecules being targeted.

Using the thin-film approach by a simple casting of the elec-trode with the rGO material, different electrode substrates, suchas GCE and SPE, have been used to detect important target mole-cules. Indeed, a chemically-reduced GNS-modified GCE has beenexplored for the simultaneous determination of morphine, nosca-pine and heroin, which are important, opiate drugs [82], and simul-taneous determination of hydroquinone (HQ) and catechol (CT)[83].

Graphene films on electrodes have usually been obtained bydrop-casting solution based on rGO obtained from chemical reduc-tion with N2H4/NH3 or other reagents from GO sheets. But the mainlimitations of this approach are the lack of control in the film thick-ness, and, clearly, the toxic chemicals involved. As consequence,nowadays, electrochemical reduction of GO has attracted greatattention because it is fast and environment friendly synthesis.


This modified electrode was used in the simultaneous determina-tion of HQ and CT [84], and NO sensing [81].

The advantages of rGO, connected with the inherent advantagesof screen-printed technology, such as disposability, have also beenexplored for detection of AA, DP and UA. Electrocatalysis from rGOon these important analytes was clearly observed [85].

Another interesting approach involved a uniform, stable andmuch-wrinkled electrophoresis-deposited (EPD) graphene film[86,87], which was utilized as an analytical platform for thedetermination of nitroaromatic explosive compounds, such as2,4,6-trinitrotoluene (TNT) [88]. This methodology was based onhigh deposition rate and throughput, good uniformity and con-trolled thickness of the films obtained, there being no need forbinders, and the simplicity of scaling up. TNT is a good p–electronacceptor and it easily adsorbs on graphene surface throughhydrogen bond and/or p–p stacking interaction with rGO. TNTsensing can therefore be attributed to those interactions withgraphene. This article [88] evaluated the analytical detection ofTNT and the electrochemical activity of the graphene-basedelectrode containing 4-nitrotoluene or 2,4-dinitrotoluene. The

Fig. 8. (a) Differential pulse voltammograms of 2 lM aloe-emodin, emodin and aloin at(pH = 7.0). (b) Possible mechanism proposed for the redox of aloe-emodin and aloin at t

authors found that the number of reduction peaks for nitroaromat-ic compounds depended on the number of nitro groups on thearomatic ring, so the graphene may have potential in theelectrochemical detection of nitroaromatic compounds with dis-tinguishable voltammogram features.

These aromatic molecules might foul the graphene electrodesbecause they adsorb in the carbon surfaces, so, in order to avoidthis fouling and to clean the nanomaterial surface, cyclic voltam-metries with the buffer of measurement are commonly employedscanning in the redox potential window. The general literaturetherefore shows that graphene has excellent repeatability andreproducibility as an electrochemical detector compared with con-ventional electrodes [89]. However, there are also some examplesshowing that graphene-modified electrodes are worse than con-ventional carbon-based electrodes [90].

But, rGO mixed with other components or embedded in a poly-mer matrix in a composite is a promising cutting edge in graphenedetectors. Indeed, as we mentioned above, the presence of poly-mers, such as Nafion or chitosan, not only stabilizes the materialon the electrode but also avoids aggregation of sheets because

(a) graphene-Nafion/GCE, (b) MWCNTs-Nafion/GCE and (c) bare GCE in 0.05 M PBShe graphene-Nafion/GCE. {Reprinted with permission of [94]}.


the positively-charged chitosan interacts with the negatively-charged graphene. A fast method for the simultaneous determina-tion of CT, resorcinol (RS) and HQ at graphene–chitosan compositefilm-modified GCE was reported [91]. Another application of thesimultaneous determination of dopamine and ascorbic acid uti-lized a green-synthesis graphene obtained using non-toxic sol-vents by reducing GO using ascorbic acid and chitosan on theGCE [92]. Furthermore, rGO-polymerization synthesis was com-pleted in one step with electro-synthesis applying cyclic sweepingon the GCE and then applied to simultaneous determination of UA,xanthine (XA) and hypoxanthine (HX) [93].

Although the properties of graphene permit in some cases thesimultaneous determination of several compounds because ofgraphene electrocatalysis on some molecules, the different p–pinteraction between target analytes and graphene allows us to dif-ferentiate the presence of two analogous structural species {e.g.,aloe-emodin and aloin were studied using a graphene-NafionGCE [94]}. It is remarkable (Fig. 8a) how the graphene-modifiedelectrode permitted current intensities in aloe-emodin and emodin(structurally analogous) much higher with graphene and MWCNTsthan with conventional GCE, and more importantly, the absence ofan oxidation peak in the case of aloin. Remarkably, this is an excel-lent example, in which the highly-electroactive surface area ofMWCNTs provided better sensitivity than an unmodified GCE,and, with the MWCNT material, the even larger electroactive sur-face area exhibited in graphene material very much enhancedthe sensitivity for both aloe-emodin and emodin. However, the

Fig. 9. Different ways carbon nanotubes (CNTs) could be unzipped to yield GNRs: (a) Insubsequent exfoliation using HCl and heat treatments; (b) chemical route, involving acbonds; (c) catalytic approach, in which metal nanoparticles ‘‘cut’’ the CNT longitudinallyCNT, and (e) physicochemical method by embedding the tubes in a polymer matrix follosheets (f). {Reprinted with permission of [26]}.

authors explained the non-oxidation peak and the absence of theoxidation peak for aloin as being due to the steric hindrance ofglycosyl group of aloin in interacting with the graphene surface,as shown in Fig. 8b. While the aloe-emodin structure easilyinteracts via p–p with the graphene structure, aloin, a non-planarand hydrophile molecule, impeded adsorption on the graphenesurface.

Moreover, other molecules have been embedded in the graph-ene structure in order to enhance response to an analyte. To stabi-lize chemically-reduced graphene, an anion porphyrin, meso-tetra(4-carboxyphenyl)porphine, was incorporated in a graphenestructure and used for highly selective, sensitive detection of DAon GCE [95]. The aromatic p–p stacking and electrostatic attractionbetween the positively-charged DA and the negatively-chargedporphyrin-modified graphene could accelerate electron transferand response to the analyte.

The recognition of chiral molecules is an important task, espe-cially in the detection of chiral drugs. A key step in selectively sens-ing chiral molecules, such as binaphthol, is to build a chiral surfacethat can identify the minute differences between the two specificenantiomers. A chiral surface was developed using the self-assem-bly method to anchor chiral osmium complex K-[Os(phen)3

(ClO4)2] onto an SL rGO film attached to the 3-aminopropyltrieth-oxysilane modified indium-tin oxide (ITO) substrate [96]. The useof SL rGO in the hybrid film greatly improved the detection sensi-tivity of chiral binaphthol, indicating that functionalized graphenefilm has promising potential in analyzing chiral molecules.

tercalation-exfoliation of MWCNTs, involving treatments in liquid NH3 and Li, andid reactions (e.g., H2SO4 and KMnO4 as oxidizing agents) that break carbon-carbonlike a pair of scissors, (d) electrical method, by passing an electric current through awed by Ar-plasma treatment. The resulting structures are either GNRs or graphene


Due to the tendency of rGO to aggregate byp–p stacking interactions,it is necessary to improve its stability. Another route to avoid this prob-lem involves inclusion of MWCNTs between graphene layers to create a3-D, porous, conductive and catalytic matrix on the electrode surface[97]. The rGO–MWCNTs hybrid materials were synthesized using aneasy chemical reduction method with polyethyleneimine (PEI) as thereductant and the dispersion of rGO-MWCNTs, which were droppedon the GCE surface to obtain rGO-MWCNTs/GCE to detect HQ, CT, p-cre-sol and nitrite simultaneously. Interestingly, when using the GCE, onlytwo oxidation peaks were found with really low intensity, but the pres-enceofMWCNTs improved theselectivity,andfourpeaksweredepicted.Also, the hybrid MWCNT-graphene material enhanced the sensitivity ofthe electrochemical measurements and the current intensity was im-proved compared to MWCNT-modified electrode.

Finally, and as regards biosensing, the main drawback in build-ing a biosensor is that proteins usually have their redox centers bur-ied deeply, so it is difficult for electrons to be transferred betweenprotein molecule and electrode surface. The question is whethergraphene has promise or not. In this sense, rGO has demonstratedits capacity to act as an electron donor, so the protein can remainstable and its direct electron-transfer rate can be enhanced. Redoxenzymes, such as GOx, or proteins, such as hemoglobin (Hb), inte-grate by combining with the graphene surface, as we discuss next.

The direct detection of glucose based on the electrocatalyticreduction of oxygen using an electrode of GOx integrated withgraphene [98] and with graphene/Nafion film was studied [99].The voltammetric results indicated that GOx assembled on graph-ene retained its native structure and bioactivity. Besides, whenthe graphene material was on the electrode, the current was doublethat in the non-modified electrodes. The higher sensitivity and cur-rents obtained using a GOx/graphene-modified electrode comparedto GOx/non-modified electrodes were due to the higher adsorptioncapacity and the stronger interaction between GOx and graphene,rather than between the oxidase and the GCE, suggesting that alarger quantity of enzyme was on the surface of the electrode.

A new biocomposite film based on graphene, zinc-oxide nano-spheres and Hb was developed for sensing hydrogen peroxide[100]. It obtained a biosensor that could retain the bioactivityand the native structure of Hb, indicating that the composite filmcould provide a favorable environment for the immobilization ofHb.

Cytochrome c embedded in a novel support matrix of a graph-ene/poly(3,4-ethylenedioxythiophene) nanocomposite on a GCEwas also studied [101]. The immobilized cytochrome c in thegraphene matrix displayed excellent direct electrochemistry andretained its biocatalytic activity toward the reduction of hydrogenperoxide.

4.3. Electrochemistry with GNRs

4.3.1. General contextAs stated at the beginning of this review, GNRs are unzipped

CNTs with structural control. Fig. 9 illustrates the different routesto open CNTs that yield GNRs [26], e.g.:

Table 4Electrochemical detection with graphenes

Graphene Structure Target molecule Interacti

GNP GO (few layers) AA, UA HydrogenCMG: GO GO (few layers) 4-NP HydrogenCMG: GO Graphene-COOH (few layers) Adenine and guanine ElectrostatCMG: rGO Graphene film TNT HydrogenCMG: rGO Graphene film Anthraquinones p–p stackiGNR rGO CT, RS, AA, L-Tyr HydrogenGNR GO HQ, LD, UA HydrogenGNR GO 1-OHP p–p

� chemical oxidation of CNTs [26];� plasma etching of CNTs embedded in a polymer film [28];� intercalation of metals [29] or nanoparticles [32].

Considering their atomic structures, graphene edges are usuallyclassified as zigzag, armchair, combined and reconstructed. Thephysical properties of finite-sized graphene nanostructures are of-ten determined by properties of the edge itself, and may substan-tially differ from those of a perfect graphene sheet.

Taking into account the most known chiral edge configurationsof CNTs, at 0� (armchair) and at 30� (zigzag), it is possible to findarmchair and zigzag GNRs, respectively. Moreover, armchair GNRsare semiconductors or conductors, depending on their width, andzigzag GNRs are always conductors or present metallic behavior,but they could also induce an energy gap, depending on the fieldstrength applied [102]. Furthermore, edge chemistry is an impor-tant characteristic of GNRs, because the edges present chemicalfunctionalities, such as carboxylic acid, carbonyl and amine. GNRsare therefore significantly more chemically reactive than crystal-line graphene, because graphene surfaces seem to be chemicallyinert and only interact with other molecules by physical adsorp-tion via p–p interaction [46].

4.3.2. Electrochemical sensingGNRs present extreme reactivity due to the existence of open-

ended graphene sheets. Thus, using graphene sheets as an electro-catalytic material for preparation of electrochemical sensors andbiosensors would be worthwhile. The presence of a larger amountof edge-plane-like defects on graphene and more sp2 domainsfacilitates the rapid detection of several interesting molecules, suchas catecholamines, neurotransmitters, NADH, H2O2, guanine, tyro-sine, and adenine, with better results than SWCNTs and MWCNTs.However, GNRs for electrochemical sensing have been used to alesser extent than other graphenes.

Functionalized GNRs obtained by unzipping using chemical oxi-dation of SWCNTs and deposition on SPEs have been evaluated fordetection of important molecules [103]. In general terms, the elec-trochemical response improved when graphene was used as elec-trochemical transductor – around double or several times morethan the signal found with SPEs. One isolated example wheregraphene did not improve the electrochemical sensing was thedetection of TNT in seawater, where no significant difference wasfound in the performance of graphite microparticles and SL, FLand ML GNRs; the sensitivities found were in the same range, being40% higher in graphite material than in SL graphene materials[104].

However, recently, the electrochemical potential of GNRs wasdemonstrated in an in-depth study using three dihydroxybenzeneisomers and other target molecules, such as UA, AA, levodopa (LD)and L-tyrosine (L-Tyr) [46]; analytical responses using reducedGNRs were 5–10-fold higher compared to the response of theGCE. Apart from the excellent responses obtained in all cases,the authors described the interaction between oxygen groupsof the GO nanoribbons and these target molecules plus the

on graphene-molecule Analytical performance features Ref.

bond Electrocatalysis and enhanced sensitivity [66]bonds plus p–p stacking Low electrode fouling [68]ic Enhanced sensitivity [69]bond and p–p stacking. Improved LOD [88]ng Enhanced sensitivity [94]bond and p–p Electrocatalysis and enhanced sensitivity [46]bond and p–p Electrocatalysis and enhanced sensitivity [46]

Low electrode fouling [105]


p–p interaction found a great deal with reduced graphene materi-als. Consequently, they opened up new opportunities for tailoringgraphene to optimize the sensing application based on thechemistry of the target molecules.

1-hydroxypyrene (1-OHP) is considered one of the metabolitesof polycyclic aromatic hydrocarbons (PAHs), and has been widelyused as a valuable urinary biomarker for evaluating human expo-sure to PAHs [105]. To reduce matrix interference and to achievethe required sensitivity, analysis of 1-OHP needs a pre-concentra-tion procedure. C18 is the most widely used adsorption material;moreover, copper phthalocyanine can selectively adsorb 1-OHPvia p–p interaction due to the small p–electron system on it.

As graphene tends to be re-aggregated due to p–p interactionsbetween graphene layers, a new route was designed by insertingpositively-charged polyhedral oligomeric silsesquioxane nanocagesinto negatively-charged GO nanoribbon layers. Apart from that,1-OHP has planar aromatic structures with a p–electron system,which interacts via p–p with graphene. When 1-OHP is pre-concentrated on the composite graphene electrode, as the concen-tration is increased, the response signal is enhanced significantly.In this case, when GO nanoribbons were deposited on the elec-trode, the response improved by a factor of 2 over that of the bareelectrode, but when 1-OHP was evaluated with the compositeframework, the response increased 12 times over that found withthe bare electrode.

GNRs have rarely been explored in making biosensors. A lesstoxic, reproducible, and easy method has been proposed to massproduce functionalized ML graphene (MLG) from MWCNTs usingonly concentrated H2SO4/HNO3. The thin film of functionalizedMLG is fabricated onto an ITO substrate by the EPD technique.Then, urease and glutamate dehydrogenase are immobilized usingethyl(dimethylaminopropyl) carbodiimide and N-hydroxy-succinimide chemistry [106]. The biochemical reaction supposesthe decomposition of urea into bicarbonate (HCO3

-) and ammo-nium ions (NH4

+), which is catalyzed by urease. Then, the additionof glutamate dehydrogenase catalyzes the reaction between NH4

+,a-ketoglutarate and NADH to obtain electrons that are transferredto the electrode.

Moreover, the integration of one model enzyme, GOx, was alsoexplored using GNRs. First, reduced GNRs, non-covalently func-tionalized with water-soluble iron(III) meso-tetrakis(N-methylpy-ridinum-4-yl) porphyrin via p–p non-covalent interaction, weredeposited on the GCE surface [107]. Using GOx as the model en-zyme, a biosensor based on the consumption of O2 was developedand could be successfully applied in the detection of glucose in hu-man serum.

Finally, in order to give a conceptual overview about the chem-istry behind the electrochemistry, Table 4 summarizes the typicalinteractions between graphenes and the target analytes towardstheir electroactive center as it is elucidated; weak interactionsare fundamental in governing the enhancement in sensing andbiosensing.

5. Outlook and perspectives

This review provides the reader with a complete overview andrealistic perspectives about synthesis, characterization and appli-cations of graphene for improved electrochemical sensing and bio-sensing. Terminology in the field of graphenes is clearly explainedto avoid misunderstanding because the term ‘‘graphene’’ refers tomultiple materials. A complete analytical characterization ofgraphene is crucial to know the morphology and the structure ofthe synthesized material.

Interestingly, this review shows how some graphenes are moresuitable than others to detect a target molecule, so that the future

perspective is to use the most appropriate graphene (tailoredgraphene) for the analysis of each target molecule. Furthermore,the interactions between these target molecules and other moie-ties or the graphene lattice should have the objective of optimizingand elucidating the best electrochemical sensing or biosensing. Tosum up, graphene holds true promise for selective, sensitive elec-trochemical sensing and biosensing.

Acknowledgements

Financial support from the Spanish Ministry of Science andInnovation (CTQ2011-28135) and the AVANSENS program of theCommunity of Madrid (P2009/PPQ-1642) are gratefully acknowl-edged. D. Aida Martin acknowledges the FPU Fellowship receivedfrom Spanish Ministry of Education, Culture and Sports.

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graphene: the cutting–edge interaction between chemistry and electrochemistry

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