Electrochemical Affinity Biosensors: Pervasive Devices with Exciting Alliances and Horizons Ahead

Abstract

Electrochemical affinity biosensors are evolving at breakneck speed, strengthening and colonizing more and more niches and drawing unimaginable roadmaps that increasingly make them protagonists of our daily lives. They achieve this by combining their intrinsic attributes with those acquired by leveraging the significant advances that occurred in (nano)materials technology, bio(nano)materials and nature-inspired receptors, gene editing and amplification technologies, and signal detection and processing techniques. The aim of this Perspective is to provide, with the support of recent representative and illustrative literature, an updated and critical view of the repertoire of opportunities, innovations, and applications offered by electrochemical affinity biosensors fueled by the key alliances indicated. In addition, the imminent challenges that these biodevices must face and the new directions in which they are envisioned as key players are discussed.

Keywords: artificial intelligence; electrochemical affinity biosensors; microfluidics; precision medicine and nutrition; wearable.

Figure 1

Ranges of clinical interest for different molecular markers. Reprinted with permission. Copyright 2017, American Chemical Society.

Figure 2

Modern electrochemical affinity biosensors provide important advances in (i) (nano)materials manufacturing and technology; (ii) bio(nano)materials and nature-inspired receptors; (iii) gene editing and amplification technologies; and (iv) signal detection and processing techniques. Figure drawn by Eloy Povedano and Víctor Ruiz-Valdepeñas Montiel, members of the research team of the authors of this perspective article.

Figure 3

(a) Electrochemical biosensors integrated in portable, wearable, and implantable devices. (b) Schematic representation of electrochemical methods and microfluidic fabrication materials for the design of microfluidic electrochemical devices. (c) Illustrative diagram of existing principles for integrating electrodes into lateral flow strips (LFS) and electrode types and modifications used in developing eLFAs. (a) Reproduced with permission. Copyright 2023, Nature Publishing Group. (b) Reprinted with permission. Copyright 2022, Springer. (c) Reprinted with permission. Copyright 2021, Springer.

Figure 4

Antifouling/protective strategies for electrochemical biosensing. Reprinted with permission. Copyright 2021, American Chemical Society.

Figure 5

Schematic display of a “dispersible electrode” for the detection of the TP53 gene mutation in blood. Reprinted with permission. Copyright 2022, Wiley-VCH.

Figure 6

Principles of voltammetric affinity biosensing at electrodes modified with nanoporous membranes functionalized with specific bioreceptors in the absence (“On” response) and presence (“Off” response) of the target biomolecule. Reproduced with permission. Copyright 2016, Elsevier.

Figure 7

Biosensor chip integrating immunoassays involving different formats and enzymatic tracers for the simultaneous determination of cortisol and insulin. Reprinted with permission. Copyright 2020, Elsevier.

Figure 8

Schemes of eLFAs for the determination of protein (a) and genetic (b) biomarkers. (a) Reprinted with permission. Copyright 2022, American Chemical Society. (b) Reprinted with permission. Copyright 2021, American Chemical Society.

Figure 9

Examples of electrochemical affinity biosensors based on the use of single (a) or multiblock (b) polyA capture probes for the determination of bacterial genetic material. (a) Reproduced with permission. Copyright 2019, American Chemical Society. (b) Reproduced with permission. Copyright 2019, American Chemical Society.

Figure 10

Bioplatform developed for the determination of serum levels of N- and S-specific total or individual immunoglobulin (Ig) isotypes (IgG, IgM, and IgA) by using MBs modified with N and in-house-expressed S ectodomains of SARS-CoV-2 variants. Amperometric detection at SPCEs. Reprinted with permission. Copyright 2022, Wiley-VCH.

Figure 11

Multiplexed microfluidic bioplatform for the simultaneous determination of viral load and ß-lactam antibiotic in nasal swabs and serum samples from COVID-19-infected patients. Reprinted with permission. Copyright 2022, Elsevier.

Figure 12

Electrochemical bioplatform for the determination of an SNP in the human genome (hypertrophic cardiomyopathy-associated SNP in the Myosin Heavy Chain 7 gene) based on an RPA strategy implemented on gold electrodes using Fc-labeled oligonucleotides. Reprinted with permission. Copyright 2022, Elsevier.

Figure 13

Smartphone assisted electrochemical biosensing for the precise diagnosis of COVID-19. Reprinted with permission. Copyright 2020, Elsevier.

Figure 14

(a) Schematic illustration of AI-IoMT-assisted fifth generation biosensors. (b) Benefits that AI and ML may bring to biosensors. (a) Reproduced with permission. Copyright 2023, Elsevier. (b) Reprinted with permission. Copyright 2020, American Chemical Society.