**2. Applications of nanocomposite-based graphene as nanosensors**

#### **2.1 Nanocomposite-based graphene oxide as fluorescence sensors**

### *2.1.1 Detection of amino acids*

People are very interested in the detection of amino acids due to their multiple biological functions. Cheng and co-workers designed and synthesized a turn-on fluorescent nanosensor based on the alizarin red aluminum (III) complex covalently binding to graphene oxide (GO) for the detection of lysine with high sensitivity and high selectivity [5]. The nanosensor was prepared by GO, Al(III) ions, and alizarin red (GO-Al-AR) by coordination mode. The as-prepared GO-Al-AR nanosensor was depicted in **Figure 2**. It showed weak fluorescence due to photo-induced electron transfer (PET). However, the fluorescence intensity of GO-Al-AR obviously enhanced upon addition of lysine. The fluorescence response of GO-Al-AR nanosensor exhibited good linear relationship with the concentrations of lysine within 25 mg/L to 250 mg/L. The detection limit was 2.0 mg/L. The premium pH value was between 6.5 and 7.2, suggesting the as-synthesized sensor is suitable for detection of lysine in living cells.

Another novel fluorescence sensing method was developed for the detection of tyramine based on CdSe/ZnS quantum dots-GO using imprinting technique [6]. The fluorescent sensor was synthesized by using CdSe/ZnS quantum dots, GO, 3-mercaptopropyltriethoxysilane (MPTES) (monomer), and tetraethyl orthosilicate (TEOS) (cross-linking agent) and targeted molecule tyramine for synthesizing molecularly imprinted polymers (MIPs), namely, Gra-QDs@MIPs. The as-synthesized sensor showed a high selectivity for the detection of tyramine. The fluorescence intensity of Gra-QDs@MIPs showed a good linear relationship with concentrations of tyramine between 0.07 and 12 mg/L. The Gra-QDs@MIPs can be used to detect tyramine in rice wine samples. A biosensor was constructed and reported based on reduced GO field-effect transistor (rGO-FET) modified by the cascading enzymes arginase and urease for the monitoring of l-arginine [7]. The rGO-FET was employed to immobilize arginase and urease through electrostatic

**175**

*Nanocomposite-Based Graphene for Nanosensor Applications*

interaction based on cationic polyethylenimine (PEI) building block. The functionalized transistors showed high sensitivity and high selectivity for the detection of l-arginine within 10–1000 μM. The detection limit was 10 μM. The sensor showed

*A schematic illustration of a turn-off/turn-on fluorescence response of GO-Al-AR to lysine.*

Bao and co-workers designed RhBPy-graphene oxide (GO) complex as a fluorescent probe for the sensitive and selective detection of doxorubicin (DOX) in MeOH/H2O solution [8]. The fluorescence of RhBPy[2] rotaxane can be efficiently quenched by addition of graphene oxide (GO) due to fluorescence resonance energy transfer (FRET), while the fluorescence of RhBPy[2] rotaxane can be recovered due to different interaction forces between DOX and RhBPy[2] rotaxane toward GO. Li et al. developed a fluorescent probe for the monitoring and detection of antibiotic virginiamycin based on GO-supported carbon quantum dots (GO/C-dots) as the signal element and molecularly imprinted polymer (MIP) as the recognition template [9]. MIP with virginiamycin as the template molecule was constructed and designed using o-aminophenol as monomer on the surface of ITO electrode deposited by GO/C-dots. The specific sensor can be obtained by removing the virginiamycin from the MIP. The GO/C-dot complex displayed strong fluorescence signal, while its fluorescence intensity declined obviously upon adsorption of virginiamycin. The specific probe showed high selectivity and high sensitivity toward

The novel doxorubicin (DOX) functionalized GO nanosensor was designed and synthesized for the detection of dopamine based on mechanism of fluorescence resonance energy transfer (FRET) [10]. The DOX showed strong property, but the

*DOI: http://dx.doi.org/10.5772/intechopen.85136*

fast response and good stability.

**Figure 2.**

*2.1.2 Detection of drug molecules*

virginiamycin, and detection limit is 1.56 × 10<sup>−</sup>11 mol/L.

*Nanorods and Nanocomposites*

**Figure 1.**

species in human serum, respectively.

*2.1.1 Detection of amino acids*

detection of lysine in living cells.

In this chapter, efforts have been made on summarizing the design, synthesis, and applications of nanocomposite-based graphene. We mainly focused on the recent development of graphene-based nanocomposites as fluorescence sensors and electrochemical sensors for the detection of biological species and non-biological

People are very interested in the detection of amino acids due to their multiple biological functions. Cheng and co-workers designed and synthesized a turn-on fluorescent nanosensor based on the alizarin red aluminum (III) complex covalently binding to graphene oxide (GO) for the detection of lysine with high sensitivity and high selectivity [5]. The nanosensor was prepared by GO, Al(III) ions, and alizarin red (GO-Al-AR) by coordination mode. The as-prepared GO-Al-AR nanosensor was depicted in **Figure 2**. It showed weak fluorescence due to photo-induced electron transfer (PET). However, the fluorescence intensity of GO-Al-AR obviously enhanced upon addition of lysine. The fluorescence response of GO-Al-AR nanosensor exhibited good linear relationship with the concentrations of lysine within 25 mg/L to 250 mg/L. The detection limit was 2.0 mg/L. The premium pH value was between 6.5 and 7.2, suggesting the as-synthesized sensor is suitable for

Another novel fluorescence sensing method was developed for the detection of tyramine based on CdSe/ZnS quantum dots-GO using imprinting technique [6]. The fluorescent sensor was synthesized by using CdSe/ZnS quantum dots, GO, 3-mercaptopropyltriethoxysilane (MPTES) (monomer), and tetraethyl orthosilicate (TEOS) (cross-linking agent) and targeted molecule tyramine for synthesizing molecularly imprinted polymers (MIPs), namely, Gra-QDs@MIPs. The as-synthesized sensor showed a high selectivity for the detection of tyramine. The fluorescence intensity of Gra-QDs@MIPs showed a good linear relationship with concentrations of tyramine between 0.07 and 12 mg/L. The Gra-QDs@MIPs can be used to detect tyramine in rice wine samples. A biosensor was constructed and reported based on reduced GO field-effect transistor (rGO-FET) modified by the cascading enzymes arginase and urease for the monitoring of l-arginine [7]. The rGO-FET was employed to immobilize arginase and urease through electrostatic

**2. Applications of nanocomposite-based graphene as nanosensors**

**2.1 Nanocomposite-based graphene oxide as fluorescence sensors**

*Structure of graphene oxide (GO) and nitrogen-doped graphene quantum dots (N-GQDs).*

**174**

**Figure 2.** *A schematic illustration of a turn-off/turn-on fluorescence response of GO-Al-AR to lysine.*

interaction based on cationic polyethylenimine (PEI) building block. The functionalized transistors showed high sensitivity and high selectivity for the detection of l-arginine within 10–1000 μM. The detection limit was 10 μM. The sensor showed fast response and good stability.

#### *2.1.2 Detection of drug molecules*

Bao and co-workers designed RhBPy-graphene oxide (GO) complex as a fluorescent probe for the sensitive and selective detection of doxorubicin (DOX) in MeOH/H2O solution [8]. The fluorescence of RhBPy[2] rotaxane can be efficiently quenched by addition of graphene oxide (GO) due to fluorescence resonance energy transfer (FRET), while the fluorescence of RhBPy[2] rotaxane can be recovered due to different interaction forces between DOX and RhBPy[2] rotaxane toward GO. Li et al. developed a fluorescent probe for the monitoring and detection of antibiotic virginiamycin based on GO-supported carbon quantum dots (GO/C-dots) as the signal element and molecularly imprinted polymer (MIP) as the recognition template [9]. MIP with virginiamycin as the template molecule was constructed and designed using o-aminophenol as monomer on the surface of ITO electrode deposited by GO/C-dots. The specific sensor can be obtained by removing the virginiamycin from the MIP. The GO/C-dot complex displayed strong fluorescence signal, while its fluorescence intensity declined obviously upon adsorption of virginiamycin. The specific probe showed high selectivity and high sensitivity toward virginiamycin, and detection limit is 1.56 × 10<sup>−</sup>11 mol/L.

The novel doxorubicin (DOX) functionalized GO nanosensor was designed and synthesized for the detection of dopamine based on mechanism of fluorescence resonance energy transfer (FRET) [10]. The DOX showed strong property, but the

fluorescence was quenched upon addition of GO (**Figure 3**). The GO-DOX complex as sensing platform showed a high selectivity toward dopamine based on different adsorption interactions between dopamine and DOX and GO. The fluorescence intensity of DOX-GO complex was partly recovered upon addition of dopamine based on competitive adsorption of DOX and dopamine on the surface of GO. The fluorescence response of DOX-GO exhibited a linear relationship with concentrations of dopamine between 8.3 × 10<sup>−</sup><sup>7</sup> M and 3.3 × 10<sup>−</sup><sup>5</sup> M in aqueous solution and 1.44 and 11.48 μmol/L in human serum, respectively. The DOX-GO can be an efficient nanosensor for sensing dopamine in human serum and living cells.

#### *2.1.3 Detection of the other small molecules*

The hexylenediamine-functionalized high fluorescent GO was constructed and prepared for the detection of hypochlorous acid (HOCl) in aqueous solution [11]. The fluorescence of functionalized GO was quenched upon addition of HOCl based on the mechanism of intramolecular charge transfer (ICT) between GO and chloramines forming by the oxidation of amino groups of functionalized GO using HOCl. The functionalized GO showed high selectivity and sensitivity for the determination of HOCl. The detection limit was 3.5 μM. The obtained sensor can be used to detect HOCl in tap water. The water-soluble and good biocompatible nanocomposite sensor was designed and prepared based on GO, Cu2+, and histidine-functionalized perylenediimide (PDI-HIS) for the determination of pyrophosphate (PPi) in biological conditions [12]. The as-synthesized sensor can be used as an efficient sensing platform in physiological conditions by fluorescence turn-on switch. The obtained sensor PDI-HIS-Cu-GO (PCG) displayed high selectivity and high sensitivity for the PPi detection with affinity constant 1.0 × 106 M<sup>−</sup><sup>1</sup> . The detection limit was 0.6 × 10<sup>−</sup><sup>7</sup> M. Compared to the PDI-HIS+Cu2+ complex, the PDI-HIS-Cu-GO nanocomposites showed higher selectivity for PPi in intracellular detection.

Cheng et al. designed a dual-output nanosensor based on GO for the detection of Ag<sup>+</sup> in aqueous solution with high sensitivity and high selectivity [13]. The nanosensor (**Figure 4**) was prepared by conjugation of GO with well-known fluorophore 1,8-diaminonaphthalene (DAN). The addition of Ag+ ions significantly

#### **Figure 3.**

*A schematic illustration of the fluorescence response of a DOX-GO complex to dopamine (a); Molecular structures of DOX (b) and dopamine (c).*

**177**

concentrations of Ag<sup>+</sup>

**Figure 4.**

*with various pHs.*

*2.2.1 Detection of proteins*

Ni(II), Cu(II), Zn(II), and Fe(III).

*Nanocomposite-Based Graphene for Nanosensor Applications*

quenched the fluorescence of resultant sensor based on the mechanism of PET, while the intensity of second-order scattering obviously enhanced. Furthermore, the intensity of as-prepared sensor showed a good linear relationship with the

*Synthetic pathway and AFM images of GAP and its fluorescence response to fivefold Ag<sup>+</sup>*

or weakly response to Na(I), K(I), Ca(II), Mg(II), Cr(III), Mn(II), Fe(II), Co(II),

Gevaerd et al. designed and synthesized imidazole-functionalized graphene oxide (GO-IMZ) as non-enzymatic electrochemical sensor for the detection of progesterone [14]. Progesterone (P4) plays an important role in the stabilization and maintenance of gestation as most important progestogen of mammals. The GO-IMZ complex as an artificial enzymatic active site was reported using voltammetric determination of progesterone. The as-synthesized sensor displayed a synergistic effect of GO nanosheets and imidazole showing the obvious enhancement on the electrochemical response of P4. The electrochemical response signal showed a linear relationship with concentrations of P4 between 0.22 and 14.0 μmol/L. The detection limit was 68 nmol/L. The limit of quantification was 210 nmol/L. The

Tomita and co-workers designed and reported the construction of high accessible and high tunable multi-fluorescent sensing system, and this sensing system presented protein fluorescent signals from a single microplate well [15]. The principal mechanism of approach was based on three single-stranded DNAs (ssDNAs) functionalized-nano-graphene oxide (nGO). The single-stranded DNAs showed different sequences and functions, and fluorophores exhibited different optical

**2.2 Nanocomposite-based graphene oxide as electrochemical sensors**

higher sensitivity was presented compared to the unmodified electrode.

ranging from 6 to 12 mg/L. The fluorescent sensor showed no

 *in aqueous solutions* 

*DOI: http://dx.doi.org/10.5772/intechopen.85136*

*Nanocomposite-Based Graphene for Nanosensor Applications DOI: http://dx.doi.org/10.5772/intechopen.85136*

**Figure 4.**

*Nanorods and Nanocomposites*

tions of dopamine between 8.3 × 10<sup>−</sup><sup>7</sup>

*2.1.3 Detection of the other small molecules*

tivity for the PPi detection with affinity constant 1.0 × 106

nanocomposites showed higher selectivity for PPi in intracellular detection. Cheng et al. designed a dual-output nanosensor based on GO for the detec-

*A schematic illustration of the fluorescence response of a DOX-GO complex to dopamine (a); Molecular* 

fluorophore 1,8-diaminonaphthalene (DAN). The addition of Ag+

fluorescence was quenched upon addition of GO (**Figure 3**). The GO-DOX complex as sensing platform showed a high selectivity toward dopamine based on different adsorption interactions between dopamine and DOX and GO. The fluorescence intensity of DOX-GO complex was partly recovered upon addition of dopamine based on competitive adsorption of DOX and dopamine on the surface of GO. The fluorescence response of DOX-GO exhibited a linear relationship with concentra-

1.44 and 11.48 μmol/L in human serum, respectively. The DOX-GO can be an efficient nanosensor for sensing dopamine in human serum and living cells.

M and 3.3 × 10<sup>−</sup><sup>5</sup>

The hexylenediamine-functionalized high fluorescent GO was constructed and prepared for the detection of hypochlorous acid (HOCl) in aqueous solution [11]. The fluorescence of functionalized GO was quenched upon addition of HOCl based on the mechanism of intramolecular charge transfer (ICT) between GO and chloramines forming by the oxidation of amino groups of functionalized GO using HOCl. The functionalized GO showed high selectivity and sensitivity for the determination of HOCl. The detection limit was 3.5 μM. The obtained sensor can be used to detect HOCl in tap water. The water-soluble and good biocompatible nanocomposite sensor was designed and prepared based on GO, Cu2+, and histidine-functionalized perylenediimide (PDI-HIS) for the determination of pyrophosphate (PPi) in biological conditions [12]. The as-synthesized sensor can be used as an efficient sensing platform in physiological conditions by fluorescence turn-on switch. The obtained sensor PDI-HIS-Cu-GO (PCG) displayed high selectivity and high sensi-

M. Compared to the PDI-HIS+Cu2+ complex, the PDI-HIS-Cu-GO

 in aqueous solution with high sensitivity and high selectivity [13]. The nanosensor (**Figure 4**) was prepared by conjugation of GO with well-known

M in aqueous solution and

M<sup>−</sup><sup>1</sup>

. The detection limit

ions significantly

**176**

**Figure 3.**

*structures of DOX (b) and dopamine (c).*

was 0.6 × 10<sup>−</sup><sup>7</sup>

tion of Ag<sup>+</sup>

*Synthetic pathway and AFM images of GAP and its fluorescence response to fivefold Ag<sup>+</sup> in aqueous solutions with various pHs.*

quenched the fluorescence of resultant sensor based on the mechanism of PET, while the intensity of second-order scattering obviously enhanced. Furthermore, the intensity of as-prepared sensor showed a good linear relationship with the concentrations of Ag<sup>+</sup> ranging from 6 to 12 mg/L. The fluorescent sensor showed no or weakly response to Na(I), K(I), Ca(II), Mg(II), Cr(III), Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), and Fe(III).
