Disease-Related Detection with Electrochemical Biosensors: A Review

Abstract

Rapid diagnosis of diseases at their initial stage is critical for effective clinical outcomes and promotes general public health. Classical in vitro diagnostics require centralized laboratories, tedious work and large, expensive devices. In recent years, numerous electrochemical biosensors have been developed and proposed for detection of various diseases based on specific biomarkers taking advantage of their features, including sensitivity, selectivity, low cost and rapid response. This article reviews research trends in disease-related detection with electrochemical biosensors. Focus has been placed on the immobilization mechanism of electrochemical biosensors, and the techniques and materials used for the fabrication of biosensors are introduced in details. Various biomolecules used for different diseases have been listed. Besides, the advances and challenges of using electrochemical biosensors for disease-related applications are discussed.

Keywords: biomolecules; disease detection; electrochemical biosensor.

Figure 1

Scheme of a biosensor with electrochemical transducer [2]. Copyright 2010. Reproduced with permission from The Royal Society of Chemistry.

Figure 2

First-generation biosensor that depends ambient oxygen with amperometric detection [2] Copyright 2010. Reproduced with permission from The Royal Society of Chemistry.

Figure 3

Schematic diagram of third-generation catalytic biosensor [2]. Copyright 2010. Reproduced with permission from The Royal Society of Chemistry.

Figure 4

Schematic of the fabrication process of the biosensor on which the multiwall CNTs (HPt-CNTs) has been decorated with unique hollow nanostructured Pt [37]. Copyright 2011. Reproduced with permission from Elsevier B.V.

Figure 5

Schematic of the fabrication process of nanostructured biosensor [52]. Copyright 2014. Reproduce with permission from Elsevier Inc.

Figure 6

(A) (22-(3,5-bis((6 mercaptohexyl)oxy)phenyl)-3,6,9,12,15,18,21-heptaoxadocosanoic acid dithiol PEG-6 carboxylate (DT2); (B) Schematic of the electrochemical immunosensor assay architecture [70]. Copyright 2011. Reproduced with permission from Elsevier B.V.

Figure 7

(A) Scheme of the experimental procedure performed. HBsAg are captured on the surface of magnetic beads, incubation with human serum that contains -HBsAg IgG antibodies and recognition with AuNPs conjugated with goat -human IgG antibodies; (B) The electrochemical detection procedure was based on the electrocatalytic hydrogen generation [6]. Copyright 2010. Reproduced with permission from Elsevier B.V.

Figure 8

(A) Scheme for the electro-copolymerization of CEA antibody–AuNP bioconjugates with o-aminophenol on polycrystalline gold electrode and the formation of CEA antibody–antigen complexes; (B) Scheme for general equivalent circuit for impedance spectra analysis in the presence of a redox probe (a) and a typical Nyquist plot of an electrochemical impedance spectra (b) [85] Copyright 2006. Reproduced with permission from Elsevier B.V.

Figure 9

The preparation process of the multi-nanomaterial EC biosensor and the procedure of CEA detection [63]. Copyright 2013. Reproduced with permission from Elsevier B.V.

Figure 10

The principle of electrochemical biosensor for FR determination based on the immobilization free and terminal protection of small molecule linked DNA [95] Copyright 2016. Reproduced with permission from Elsevier B.V.

Figure 11

Scheme of the sandwich assay for electronic detection of nucleic acids. The gold electrode was coated with a SAM including (1) DNA-alkanethiols that contain the capture probe sequence; (2) molecular wires, which provide a pathway for electron transfer between the Fc and the gold in response to potential changes at the electrode; and (3) alkanethiols terminated in polyethylene glycol insulator, which serve as insulators to block access of redox species in solution to the electrode, including free signaling probes. A target nucleic acid is shown annealed to a capture probe and a Fc-labeled signaling probe [106]. Copyright Reproduced with permission from American Society for Investigative Pathology and the Association for Molecular Pathology.

Figure 12

Diagram of DNA tetrahedral probe [34]. Copyright 2015. Reproduced with permission from American Chemical Society.

Figure 13

Scheme of the electrochemical sensing system based on the dual strategy of ATP-dependent enzymatic ligation reaction and cyclic amplification based on self-cleaving DNAzyme [89] Copyright 2014. Reproduced with permission from Elsevier B.V.

Figure 14

Principle of miRNA electrochemical detection based on mismatched catalytic hairpin assembly amplification [114]. Copyright 2015. Reproduced with permission from Elsevier B.V.

Figure 15

Mechanism of the label-free and enzyme-free homogeneous electrochemical strategy based on HCR amplification for miRNA Assay [116] Copyright 2015. Reproduced with permission from American Chemical Society.

Figure 16

The scheme of MUC1 detection with the HO switch. (A) The biotin is shielded and thus inaccessible to the streptavidin in the absence of MUC1. Then, a very limited background current (inset) was observed (curve a); (B) The disruption of the stem-loop makes the biotin exposed upon target binding. Then, the biotin along with the dually labelled aptamers is easily captured by the streptavidin-modified electrode (curve b) [129]. Copyright 2013. Reproduced with permission from Elsevier B.V.

Figure 17

Illustration of urine-based detection of nucleic acids and proteins. (A) Schematic of pathogen identification based on sandwich hybridization of bacterial 16S rRNA with capture and detector oligonucleotide probes; (B) Schematic of immunoassay based on sandwich detection host urinary protein with capture and detector antibodies [133].