A concise overview of advancements in ultrasensitive biosensor development

Abstract

Electrochemical biosensing has evolved as a diverse and potent method for detecting and analyzing biological entities ranging from tiny molecules to large macromolecules. Electrochemical biosensors are a desirable option in a variety of industries, including healthcare, environmental monitoring, and food safety, due to significant advancements in sensitivity, selectivity, and portability brought about by the integration of electrochemical techniques with nanomaterials, bio-recognition components, and microfluidics. In this review, we discussed the realm of electrochemical sensors, investigating and contrasting the diverse strategies that have been harnessed to push the boundaries of the limit of detection and achieve miniaturization. Furthermore, we assessed distinct electrochemical sensing methods employed in detection such as potentiometers, amperometers, conductometers, colorimeters, transistors, and electrical impedance spectroscopy to gauge their performance in various contexts. This article offers a panoramic view of strategies aimed at augmenting the limit of detection (LOD) of electrochemical sensors. The role of nanomaterials in shaping the capabilities of these sensors is examined in detail, accompanied by insights into the chemical modifications that enhance their functionality. Furthermore, our work not only offers a comprehensive strategic framework but also delineates the advanced methodologies employed in the development of electrochemical biosensors. This equips researchers with the knowledge required to develop more accurate and efficient detection technologies.

Keywords: biosensor; electrochemical sensor; limit of detection; miRNA; nanoparticles.

FIGURE 1

Diversity of nanomaterials, electrode selection, ligand variability, and electrochemical sensing techniques in the framework of biosensor development for detecting various miRNAs.

FIGURE 2

Simplified schemes of the fabrication of ultrasensitive biosensors. (A) Schematic illustration of the preparation of the CDNM via target-triggered TSDRs and the walking process of the CDNM in the presence of target miRNA (Li et al., 2023). (B) Schematic of Ag@N,O-C BLHS synthesis, and electrochemical sensing mechanism for ctDNA detection sensitized with Ag@N, O-C BLHS driven by DNA walker (Qin et al., 2023). (C) Construction of a ratiometric electrochemical sensor based on the 3D-DNA nanomachine with multiple hybridization and cleavage cycles for miRNA detection (Gao et al., 2022). (D) Fabrication scheme for the Ag NPs/SnO2 QDs/MnO2 NFs based-ECL biosensor for miR-21 detection (Yang et al., 2021a). (E) Creation of ABEI@AuPd NPs sensor with DNA nanomachines walking freely on ECL electrodes for the detection of miR-141 (Wang et al., 2021a). (F) BP-CdTe QDs biosensor construction and GOx conjugation to S1 for miR-126 detection (Zhao et al., 2021). (G) Schematic based on the CHA-tripedal DNA walker strategy along with the walking process of the tripedal DNA walker on the electrode of ECL for the detection of miRNA-21 (Wang et al., 2020a). (H) AF-PtNPs@Ru (dcbpy)^2/3+ assembly with 3D DNM using target recycling amplification technology and the multiple ECL-RET biosensor for the detection of miR-141 (Wang et al., 2020b). (I) Schematic illustration of the preparation of ST, its assembly steps, and signal conversion mechanism of the ratiometric biosensor for detecting miR-155 (Liu et al., 2021). (J) DPA@Pe biosensor fabrication strategy based on affinity switch using CHA and RCA amplification strategy for miR-21 detection (Liao et al., 2020). Abbreviations: AA, ascorbic acid; A₁ and A₂, helper SSDNA; A₃, secondary target DNA; ABEI, N-(4-Aminobutyl)-N-(elthylisoluminol); (A:C-MB:B), three stranded substrate complex; AF, Alexa fluor; [Ag(Bin)]_n, silver based benzimidazole polymer; AuNP, gold nanoparticles; bioHP1, biotinylated hairpin probe 1; bioHP2, biotinylated hairpin probe 2; BP, black phosphorus; BSA/Fc/S2, bovine serum albumin labeled with ferrocene and DNA strand S2; CDNM, controlled 3D DNA nanomachine; CHA, Catalytic hairpin assembly; CP, capture probe; CS, chitosan; CTAB, hexyltrimethyl ammonium bromide; CtDNA, circulating tumor DNA; CTQDs, CdTe quantum dots; dep/Au, electrodeposited with gold particles; 3DNM, 3D DNA nanomachine; DM, DNAzyme; dNTPs, deoxyribose nucleotide triphosphate; DPA, 9,10-diphenylanthracene; DPV, differential pulse voltammetry; 3D-rGO, three dimensional reduced graphene oxide; DW, DNA walker; ECL, electrochemiluminescence; Fc, Ferrocene; (Fc-DNA-Fc), double labeled ferrocene quencher probes; F, fuel; GCE, glassy carbon electrode; GH2, graphene oxide with hairpin 2; GH3, graphene oxide with hairpin 3; G-quad, G-quadruplex structure; H, hairpin chain; Hemin-G-quStr, Hemin/G-quadruplex structures; HDPC, chlorohexadecyl pyridine; HPdNs, hollow palladium nanospheres; HT, hexanethiol; LR, linear range; MBS, maleimidobenzoic acid N-hydroxy-succinimide ester; MCs, microcrystals; MCH, modified carbon hairpin chain; miR, microRNA; Mg⁺², magnesium ion cofactor; MMB, magnetic micro beads; MT, mimic targets; NC1, Nanocomposite 1; NC2, Nanocomposite 2; NC3, nanocomposite3; NFs, nanoflowers; NPs. Nanoparticles; NS, nanosheet; P, protected strand; Pe, perylene; PFO, poly (9,9-di-n-octylflurenyl-2,7-diyl); Phi29, DNA polymerase; PP, protect probe; PSC, polystyrene microspheres; PtNCs, polyethyleneamine platinum nanoclusters; PVP, polyvinyl pyrrolidone; QDS, quantum dots; RP, reference probe; Ru (dcbpy)^2/3+, tris (4, 4′-dicarboxyylic acid - 2,2′-bipyridyl) ruthenium II; S1, single strand; SA, streptavidin; SH, thiol modified hairpin; SP, signal probe; ss DNA, single strand DNA; ST, selected target; SWV, square wave voltammetry.