Development strategies of conducting polymer-based electrochemical biosensors for virus biomarkers: Potential for rapid COVID-19 detection

Abstract

Rapid, accurate, portable, and large-scale diagnostic technologies for the detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) are crucial for controlling the coronavirus disease (COVID-19). The current standard technologies, i.e., reverse-transcription polymerase chain reaction, serological assays, and computed tomography (CT) exhibit practical limitations and challenges in case of massive and rapid testing. Biosensors, particularly electrochemical conducting polymer (CP)-based biosensors, are considered as potential alternatives owing to their large advantages such as high selectivity and sensitivity, rapid detection, low cost, simplicity, flexibility, long self-life, and ease of use. Therefore, CP-based biosensors can serve as multisensors, mobile biosensors, and wearable biosensors, facilitating the development of point-of-care (POC) systems and home-use biosensors for COVID-19 detection. However, the application of these biosensors for COVID-19 entails several challenges related to their degradation, low crystallinity, charge transport properties, and weak interaction with biomarkers. To overcome these problems, this study provides scientific evidence for the potential applications of CP-based electrochemical biosensors in COVID-19 detection based on their applications for the detection of various biomarkers such as DNA/RNA, proteins, whole viruses, and antigens. We then propose promising strategies for the development of CP-based electrochemical biosensors for COVID-19 detection.

Keywords: COVID-19; Conducting polymer; Electrochemical biosensor; Immuno-sensor; SARS-CoV-2.

Graphical abstract

Fig. 1

Schematic summary of the main content of the study.

Fig. 2

Schematic structure of SARS-Cov-2 and its biomarkers for diagnosis.

Fig. 3

Schemes of immobilization strategies: (1) physical adsorption, (2) electrochemical entrapment, (3) covalent attachment.

Fig. 4

(a) Schematic illustration of the preparation process of antifouling RNA biosensors using peptides for surface modification of PANI polymer. Reproduced with permission from (Wang et al., 2020a); (b) Biosensor based on PEDOT grafted sialyllactose for human influenza A virus detection. Reproduced with permission from (Hai et al., 2017); (c) Functionalization of PEDOT for DNA biosensor using CuAAC reaction. Reproduced with permission from (Galán et al., 2015).

Fig. 5

(a) CP nanostructures for electrochemical biosensors: (i) nanotubes (ii) nanowires and (iii) microspheres Reproduced with permission from (Xia et al., 2010); (b) Proposed approaches for the design of nanowire-based electrochemical biosensors. Reproduced with permission from (Travas-Sejdic et al., 2014); (c) Schematic illustration of PPy nanowires-based electrochemical biosensor for virus detection: (i) T7 antibody-functionalized PPy nanowire, (ii) BSA blocking, and (iii) virus phage interacts with probes on the nanowire surface. Reproduced with permission from (Shirale et al., 2010).

Fig. 6

(a) Preparation process of PEDOT microspheres using ultrasonic spray polymerization, (b) SEM and TEM of three types of PEDOT microspheres: (i, ii) solid microspheres (iii, iv) porous microspheres, and (v, vi) hollow microsphere. Reproduced with permission from (Zhang and Suslick, 2015).

Fig. 7

Fabrication process of the immuno-sensor based on porous PANI. Reproduced with permission from (Liu et al., 2018).

Fig. 8

Composites based on the integration of conducting polymer and carbon-based materials for COVID-19 electrochemical biosensors: (1) CPs and CNT composite; (2) CPs and MWCNT composite; (3) CPs and graphene composite; and (4) CPs and GO composite.

Fig. 9

(a) Schematic illustration of an electrochemical biosensor based on PPy/AuNPs composite for RNA detection (b) Fabrication procedure of a label-free biosensor based on PPy/AgNF composite for RNA detection. Reproduced with permission from (Kangkamano et al., 2018); (c) Immuno-sensor based on Fe₂O₃-PEDOT composites for detecting pathogens. Reproduced with permission from (Kumar et al., 2019).

Fig. 10

Schematic illustration of the preparation of a PEDOT/PEG conducting copolymer-based electrochemical biosensor for detecting protein. Reproduced with permission from (Cui et al., 2016).

Fig. 11

(a) Preparation of a PANI/PA-based electrochemical biosensor with antifouling ability for miRNA detection. Reproduced with permission from (Yang et al. 2020b); (b) Patterning of pure PEDOT:PSS hydrogels: Free-standing pure PEDOT:PSS pattern and robust laminate of pure PEDOT:PSS hydrogel pattern. Reproduced with permission from (Lu et al., 2019).

Fig. 12

(a) Flexible DNA biosensor based on the integration of PEDOT:PSS-based OECT and flexible microfluidic systems: (i) fabrication process, (ii) photographs of the bent. Reproduced with permission from (Lin et al., 2011); (b) Flexible biosensors for different bending radius during bending and relaxing. Reproduced with permission from (Kwon et al., 2013); (c) PAAm/PANI-based hydrogel as an electronic skin fixed on forefinger of a human hand (Duan et al., 2016); (d) Graphene-based biosensor device for detecting SARS-CoV-2. Reproduced with permission from (Seo et al., 2020b).