Graphene-based biosensors

Abstract

Reliable data obtained from analysis of DNA, proteins, bacteria and other disease-related molecules or organisms in biological samples have become a fundamental and crucial part of human health diagnostics and therapy. The development of non-invasive tests that are rapid, sensitive, specific and simple would allow patient discomfort to be prevented, delays in diagnosis to be avoided and the status of a disease to be followed up. Bioanalysis is thus a progressive discipline for which the future holds many exciting opportunities. The use of biosensors for the early diagnosis of diseases has become widely accepted as a point-of-care diagnosis with appropriate specificity in a short time. To allow a reliable diagnosis of a disease at an early stage, highly sensitive biosensors are required as the corresponding biomarkers are generally expressed at very low concentrations. In the past 50 years, various biosensors have been researched and developed encompassing a wide range of applications. This contrasts the limited number of commercially available biosensors. When it comes to sensing of biomarkers with the required picomolar (pM) sensitivity for real-time sensing of biological samples, only a handful of sensing systems have been proposed, and these are often rather complex and costly. Lately, graphene-based materials have been considered as superior over other nanomaterials for the development of sensitive biosensors. The advantages of graphene-based sensor interfaces are numerous, including enhanced surface loading of the desired ligand due to the high surface-to-volume ratio, excellent conductivity and a small band gap that is beneficial for sensitive electrical and electrochemical read-outs, as well as tunable optical properties for optical read-outs such as fluorescence and plasmonics. In this paper, we review the advances made in recent years on graphene-based biosensors in the field of medical diagnosis.

Keywords: biosensors; diagnostics; graphene.

Figure 1.

Construction of graphene-based biosensor interfaces: (a) current preparation methods; (b) chemical structures of different graphene derivatives widely used for biosensing; (c) methods for the transfer of graphene-based materials to solid substrates; (b) scanning electron micrograph (SEM) images of graphene-coated interfaces using different deposition methods and different graphene precursors. GC, glassy carbon electrode; PDDA, poly(diallyldimethylamonium). (Online version in colour.)

Figure 2.

G-based sensors of small molecules such as glucose and dopamine: (a) CVD graphene modified with glucose oxidase (GO_x) using a bifunctional pyrene linker for the construction of a G-FET for glucose (reprinted with permission from Huang et al. [23]); (b) non-enzymatic glucose sensor operating under basic conditions based on N-doped porous-reduced graphene oxide loaded with CuO NPs (N-prGO-Cu NPs) (reprinted with permission from Maaoui et al. [27]); (c) graphene quantum dots (GQDs) modified with boronic acid-substituted bipyridine ligands for non-enzymatic glucose sensing under physiological conditions (reprinted with permission from Li et al. [14]); (d) differential pulse voltammetry of ascorbic acid (1 mM), serotonin (1 mM) and dopamine (1 mM) and a mixture of all three (0.1 M) on glassy carbon electrodes modified with hydrazine-reduced GO (reprinted with permission from Alwarappan et al. [28]). (Online version in colour.)

Figure 3.

DNA sensing with G-biosensors: (a) single DNA electrochemical biosensing using graphene nanowalls (GNWs): SEM image of GNWs formed by electrophoretic deposition onto graphite rod, differential pulse voltammograms of dsDNA (0.1 µM) in phosphate-buffered saline (0.1 M, pH 7) on different interfaces (reprinted with permission from Akhavan et al. [17]); (b) mechanism of DNA interaction with GO (reprinted with permission from Liu et al. [31]) and FRET-based DNA sensing using GQDs and GO (reprinted with permission from Qian et al. [16]); (c) graphene–SPR-based DNA sensing: transmission electron micrograph (TEM) image of a gold nanostructure together with the change in SPR signal upon incubation with cDNA and mismatched DNA (reprinted with permission from Zagorodko et al. [11]). (Online version in colour.)

Figure 4.

G-biosensors for protein sensing using: (a) an electrochemical sensor for folic acid protein: DPV upon addition of increasing concentrations of folic acid proteins (reprinted with permission from He et al. [10]); (b) G-FET for the analysis of prostate biomarkers (reprinted with permission from Kim et al. [22]); (c) graphene–SPR-based sensing of lysozyme: atomic force microscopy image of an Au–(PDDA/GO)₂ interface modified with Micrococcus lysodeiktikus and the change in SPR responses to different concentrations of lysozyme added to fetal bovine serum (reprinted with permission from Vasilescu et al. [19]); (d) concentration-dependent SERS spectra from a tau protein-conjugated nanoplatform after magnetic separation together with an SEM image of a core-shell NP-attached hybrid GO and HR-TEM image (reprinted with permission from Demeritte et al. [21]). BSA, bovine serum albumin; PEG, polyethylene glycol. (Online version in colour.)