Graphene-Based Sensors for the Detection of Bioactive Compounds: A Review

Abstract

Over the last years, different nanomaterials have been investigated to design highly selective and sensitive sensors, reaching nano/picomolar concentrations of biomolecules, which is crucial for medical sciences and the healthcare industry in order to assess physiological and metabolic parameters. The discovery of graphene (G) has unexpectedly impulsed research on developing cost-effective electrode materials owed to its unique physical and chemical properties, including high specific surface area, elevated carrier mobility, exceptional electrical and thermal conductivity, strong stiffness and strength combined with flexibility and optical transparency. G and its derivatives, including graphene oxide (GO) and reduced graphene oxide (rGO), are becoming an important class of nanomaterials in the area of optical and electrochemical sensors. The presence of oxygenated functional groups makes GO nanosheets amphiphilic, facilitating chemical functionalization. G-based nanomaterials can be easily combined with different types of inorganic nanoparticles, including metals and metal oxides, quantum dots, organic polymers, and biomolecules, to yield a wide range of nanocomposites with enhanced sensitivity for sensor applications. This review provides an overview of recent research on G-based nanocomposites for the detection of bioactive compounds, providing insights on the unique advantages offered by G and its derivatives. Their synthesis process, functionalization routes, and main properties are summarized, and the main challenges are also discussed. The antioxidants selected for this review are melatonin, gallic acid, tannic acid, resveratrol, oleuropein, hydroxytyrosol, tocopherol, ascorbic acid, and curcumin. They were chosen owed to their beneficial properties for human health, including antibiotic, antiviral, cardiovascular protector, anticancer, anti-inflammatory, cytoprotective, neuroprotective, antiageing, antidegenerative, and antiallergic capacity. The sensitivity and selectivity of G-based electrochemical and fluorescent sensors are also examined. Finally, the future outlook for the development of G-based sensors for this type of biocompounds is outlined.

Keywords: ascorbic acid; bioactive compound; curcumin; gallic acid; graphene; graphene oxide; hydroxytyrosol; melatonin; oleuropein; resveratrol; tannic acid; tocopherol.

Scheme 1

Representation of bottom-up and top-down approaches for G synthesis. GDQ: graphene quantum dots.

Scheme 2

Molecular structures of Graphene, Graphene Oxide, and Reduced Graphene Oxide.

Figure 1

(a) TEM images of graphene quantum dots (GQDs) of different sizes and the photoluminescence spectrum excited at 400 nm. (b,c) High-resolution transmission electron microscopy (HRTEM) images of GQDs. Taken from Wu et al. [32].

Scheme 3

Basic representation of a chemical sensor.

Scheme 4

Chemical structure of the selected antioxidants.

Figure 2

Representation of the anchoring of polymer chains onto graphene (G) via “grafting-to”, “grafting-from”, and “grafting-through” approaches. Adapted from Eskandari et al. [145].

Figure 3

Graphene-coated carbon screen-printed electrode (G-CSPE) with the three-electrode system: a reference electrode, a working electrode, and an auxiliary or counter electrode.

Figure 4

Differential pulse voltammetry (DPVs) for the determination of melatonin (MLT) at the N-reduced graphene oxide (rGO)/CuCo₂O₄/carbon paste electrode (CPE) in the presence of 2 mM dopamine and tryptophan. Taken from Tadayon et al. [166].

Figure 5

Schematic illustrations of the preparation of ZrO₂/Co₃O₄/rGO nanocomposite and oxidation mechanisms of gallic acid (GA), caffeic acid (CA), and protochatechuic acid (PA). Taken from Puangjan et al. [172].

Figure 6

Diagram showing the formation of Au-nanoparticles (NPs) using GA under low-temperature sonication conditions. Adapted from Ganesh et al. [173].

Figure 7

Schematic illustration of the photoelectrochemical process for GA oxidation at a polyaniline (PANI)–rGO–TiO₂ modified electrode. Taken from Ma et al. [175].

Figure 8

Fluorescence emission spectra of GQDs in the presence of different tannic acid (TA) concentrations, from 0.1 to 50 µM. The inset shows the linear plot of the intensity versus TA concentration. Taken from Sinduja et al. [179].

Figure 9

Displacement assay for resveratrol using calix(6)arene (CX6)-modified reduced graphene oxide (CX6@RGO) against a fluorescent dye. Taken form Li et al. [185].

Figure 10

Cyclic voltammetric (CV) curves of 0.1 mM oleuropein (OL) on a TiO-rGO electrode at different scan rates from 25 to 1000 mV s⁻¹. Taken from Yazar et al. [195].

Figure 11

Representation of the synthesis of GO/QDs@molecular imprinted polymers (MIP) by a one-pot room temperature synthesis strategy with reverse microemulsion polymerization. Taken from Liu et al. [200].

Figure 12

Cyclic voltammograms of (a) Bare graphite (b) Bare graphite with 5 mM ascorbic acid (AA) (c) NiO/G electrode in 0.1 M phosphate-buffered saline (PBS), pH 7.0 (d) NiO/G with 5 mM AA in 0.1 M buffer solution. Taken from Swamy et al. [203].

Figure 13

TEM images and X-ray diffraction (XRD) pattern of RGO/polydopamine(PDA)/Au nanohybrids. Taken from Shi et al. [207].

Figure 14

Representation of the synthesis of metal nanoparticles (NPs)-grafted N-doped functionalized graphene (NFG)/polyaniline (PANI) nanocomposites. Taken from Salahandish et al. [209].

Figure 15

Schematic representation of the synthesis of l-cystein/rGO/Ru@AuNPs. Taken from Kotan et al. [220].