Pathogen detection with electrochemical biosensors: Advantages, challenges and future perspectives

Abstract

Detection of pathogens, e.g., bacteria and viruses, is still a big challenge in analytical medicine due to their vast number and variety. Developing strategies for rapid, inexpensive, specific, and sensitive detection of the pathogens using nanomaterials, integrating with microfluidics devices, amplification methods, or even combining these strategies have received significant attention. Especially, after the health-threatening COVID-19 outbreak, rapid and sensitive detection of pathogens became very critical. Detection of pathogens could be realized with electrochemical, optical, mass sensitive, or thermal methods. Among them, electrochemical methods are very promising by bringing different advantages, i.e., they exhibit more versatile detection schemes and real-time quantification as well as label-free measurements, which provides a broader application perspective. In this review, we discuss the recent advances for the detection of bacteria and viruses using electrochemical biosensors. Moreover, electrochemical biosensors for pathogen detection were broadly reviewed in terms of analyte, bio-recognition and transduction elements. Different fabrication techniques, detection principles, and applications of various pathogens with the electrochemical biosensors were also discussed.

Keywords: Bacteria; Biosensor; Electrochemical biosensor; Electrochemical detection; Pathogen detection; Virus.

Fig. 1

(A) Schematic representation of the development of chitosan (Chi), multi-walled carbon nanotubes (MWCNTs), and gold nanoparticles (AuNPs) with polypyrrole (Ppy) modified electrodes for the detection of E. coli. (B) Cyclic voltammograms of different modified electrodes: (a) Chi-PPy, (b) bara electrode, (c) Chi-PPy-MWCNT, (d) Chi-PPy-MWCNT-AuNPs (1:1), (e) Chi-PPyMWCNT-AuNPs (1:2) in 5.0 mM K₃[Fe(CN)₆]/K₄[Fe(CN)₆] solution at a scan rate of 50 mV/s. (C) Selectivity of the developed sensor toward other bacteria species. Reprinted from [21] with permission: Copyright © 2017 Elsevier B.V.

Fig. 2

Assembling steps of the label-free immunosensor for the detection of E. coli based on the application of antibody AG nano-flowers on Au electrodes. Reprinted from [25] with permission: CC BY 4.0 open access publication.

Fig. 3

Schematic illustration of the electrode fabrication and the detection scheme of the electrochemical immunosensor based on laser-induced graphene working electrode modified with linkers and capturing antibodies to detect Salmonella bacteria in chicken food products. Reprinted from [12] with permission: Copyright © 2020 American Chemical Society.

Fig. 4

Schematic illustration of (A) the preparation of Fe₃O₄@Ag/GQD nanoparticles and, (B) modification of GCE electrodes for the detection of Mycobacterium tuberculosis using a sandwich-type electrochemical immunosensor. Reprinted from [32] with permission: Copyright © 2018 Elsevier B.V.

Fig. 5

(A) Synthesis of the nano-sheet and the fabrication of the lab-on-chip device for the detection of Salmonella typhimurium in nourishment samples using an electrochemical immunosensing method. (B) EIS results of fMoS₂-NS/ITO and anti-S. typhimurium/f-MoS₂-NS/ITO microfluidic immunochip in K₃[Fe(CN)₆]/K₄[Fe(CN)₆] solution. Reprinted from [33] with permission: Copyright © 2017 Elsevier B.V.

Fig. 6

(A) Schematic illustration of the preparation of the CagA antigen@ZnO-T/SP-AuE immunosensor. (B) CV of CagA antigen coated modified electrodes with different CagA-antibody concentrations between in 5 mM [Fe(CN)₆]^3−/4−electrolyte. Reprinted from [38] with permission: Copyright © 2018 American Chemical Society.

Fig. 7

Schematic illustration of the development of covalently immobilized anti-E. coli based impedimetric immunosensor for E. coli detection. Reprinted from [40] with permission: © 2020 Springer Nature Switzerland AG.

Fig. 8

(A) Schematic illustration of the electrochemical DNA biosensor for the detection of Enterobacteriaceae bacteria. (B) EIS, and (C) SWVs for (a) bare electrode, (b) capture DNA modified electrode, (c) capture DNA modified electrode after the reaction with target DNA and Exo III, and (d) further reaction with detection probe. Reprinted from [47] with permission: Copyright © 2013 Elsevier B.V.

Fig. 9

Schematic illustration of the development of rGO and TiO₂ modified electrochemical aptasensor for the determination of S. Typhimurium. Reprinted from [49] with permission: Copyright © 2020 Elsevier B.V.

Fig. 10

(A) Schematic illustration of the development of ZnO/AuNP modified electrochemical DNA biosensor for the detection of Mycobacterium tuberculosis. (B) Comparison of the peak current in DPV between ZnO modified and ZnO-free electrodes in the absence (a,b) and presence (c,d) of complementary DNA. Reprinted from [52] with permission: Copyright © 2020 Elsevier B.V.

Fig. 11

Schematic illustration for the development of electrochemical immunosensor for the detection of FMV. Reprinted from [66] with permission: Copyright © 2018 Elsevier B.V.

Fig. 12

Scheme for the development of electrochemical DNA biosensor for the determination of Ebola virus. Reprinted from [68] with permission: Copyright © 2018 Elsevier B.V.

Fig. 13

Schematic illustration of the label-free electrochemical immunosensor employing modified GCE electrodes with PtPd nanocubes on molybdenum disulfide nano-sheet (MoS₂) and hepatitis B antigen. Reprinted from [73] with permission: Copyright © 2019 Elsevier B.V.

Fig. 14

(A) Conjugation of PAMAM dendrimers-encapsulated silver nanocomposites (AgDNCs) and DNA-encapsulated Ag nanoclusters (DNA/AgNCs). (B) Modification steps of the gold working electrode and amplification of target DNA using an enzyme-based method. Reprinted from [74] with permission: Copyright © 2019 Elsevier B.V.