Recent advances and future prospects of the potential-resolved strategy in ratiometric, multiplex, and multicolor electrochemiluminescence analysis

Abstract

The potential-resolved strategy has gradually demonstrated its distinct values in electrochemiluminescence (ECL) bio-sensing due to its superior characteristics, such as low instrument requirement, short assay time, and improved sample throughput, in conjunction with spatial- and spectrum-resolved techniques. It has recently been widely generalized into versatile multiple-signal ECL analytic platforms, especially in ratiometric and multiplex ECL sensors, in accordance with some specific principles. Furthermore, luminophore pairs with potential- and wavelength-resolved properties have been utilized to visualize biosensors that display multiple colors depending on analyte concentration. However, only a few comprehensive reports on the principles, construction, and application of various ECL sensors in potential-resolved schemes have been published. This review aims to recount the potential-resolved strategy applying to (a) ratiometric ECL sensors, (b) multiplex ECL sensors, and (c) multicolor ECL sensors and to discuss the distinctions and connections among the application principles of these strategies. Finally, the future prospects of ECL-based potential-resolved analysis are explored.

Keywords: electrochemiluminescence; multicolor electrochemiluminescence sensors; multiplex electrochemiluminescence sensors; potential-resolved strategy; ratiometric electrochemiluminescence sensors.

Scheme 1

Illustration of the application of potential-resolved strategy in ratiometric ECL sensors based on (A) ECL-RET strategy, adapted with permission from , copyright 2020 Elsevier B.V., (B) competition strategy, adapted with permission from , copyright 2020 American Chemical Society, (C) enzymatic strategy, adapted with permission from , copyright 2017 American Chemical Society, (D) single luminophore strategy, adapted with permission from , copyright 2020 Royal Chemical Society, (E) internal standard strategy, adapted with permission from , copyright 2016 Elsevier B.V.; multiplex ECL sensors based on (F) bilateral luminescence, adapted with permission from , copyright 2020 Elsevier B.V., (G) unilateral low-potential luminescence, adapted with permission from , copyright 2021 Elsevier B.V., (H) spatial-resolved system, adapted with permission from , copyright 2019 Royal Chemical Society, (I) concentration-controlled measure, adapted with permission from , copyright 2014 American Chemical Society, (J) real-time & on-spot detection, adapted with permission from , copyright 2013 Elsevier B.V.; and multicolor ECL sensors based on (K) concomitant metal complex, adapted with permission from , copyright 2016 Royal Chemical Society, (L) single luminescent clusters, adapted with permission from , copyright 2020 American Chemical Society.

Figure 1

Schematic of the potential resolved ECL-RET biosensors based on (A) the ECL-RET system with luminophores with high color purity and facile band controllability. Adapted with permission from , copyright 2020 American Chemical Society; (B) universal enhancer or quencher. Adapted with permission from , copyright 2018 Elsevier B.V.; and (C) signal regulation materials. Adapted with permission from , copyright 2016 Elsevier B.V.

Figure 2

Schematic of potential-resolved competition-strategy sensors with (A) H₂O₂ as the co-reactant. Adapted with permission from , copyright 2020 Springer; and (B) dissolved O₂ as the co-reactant. Adapted with permission from , copyright 2020 American Chemical Society. (C) Steric hindrance strategy. Adapted with permission from , copyright 2019 American Chemical Society. (D) Immune competition mechanism. Adapted with permission from , copyright 2016 Elsevier B.V.

Figure 3

Schematic of the potential-resolve enzymatic strategy sensors based on the reverse variation of the substrate O₂ and H₂O₂ in (A) the AChE-ChOx enzyme system. Adapted with permission from , copyright 2017 American Chemical Society; single H₂O₂ substrate as the bifunctional moderator in (B) the glucose oxidase system. Adapted with permission from , copyright 2020 Elsevier B.V.; and (C) the AChE system. Adapted with permission from . Copyright 2021 American Chemical Society.

Figure 4

Schematic of single luminophore ratiometric ECL sensors based on dual co-reactants. (A) G-C₃N₄ and Au-g-C₃N₄ as the co-reactants of Ru(bpy)₃²⁺ for Hg²⁺ detection. Adapted with permission from , copyright 2020 Royal Chemical Society. (B) K₂S₂O₈ and TEA as the co-reactants of porous g-C₃N₄ NSs for AFP detection. Adapted with permission from , copyright 2020 Royal Chemical Society. Single-luminophore ratiometric ECL sensors based on (C) C-dots as the single co-reactant of Ru(bpy)₃²⁺ for the determination of the antibiotic TC. Adapted with permission from , copyright 2019 Springer.

Figure 5

Schematic of the internal standard ratiometric ECL sensor with the physically separated double disk electrode (WE1 and WE2) in (A) a dual-disk inner reference ratiometry system. Adapted with permission from , copyright 2020 Royal Chemical Society; (B) a DDCE label-free system. Adapted with permission from , copyright 2017 Elsevier B.V. Schematic of the internal standard ratiometric ECL sensor with the physically separated double disk electrode (WE1 and WE2) with single electrode assembled with an internal reference signal probe and working signal probe in (C) a ratiometric antifouling ECL biosensor based on PAMAM-CIZS/ZnS QDs. Adapted with permission from , copyright 2020 Elsevier B.V.; and (D) with photothermal amplification strategies. Adapted with permission from , copyright 2019 Elsevier B.V.

Figure 6

Schematic of sensors for simultaneous multimarker detection based on bilateral anodic-and-cathodic-potential luminescence with (A) L012 and g-C₃N₄ as the luminophore pairs for the in situ detection of apoptosis factors. Adapted with permission from , copyright 2019 American Chemical Society. (B) Luminol and g-C₃N₄ as the signal probe. Adapted with permission from , copyright 2021 Elsevier B.V. Biosensors based on unilateral low-potential luminescence with (C) the low-potential cathode luminophore PDI and co-reactant K₂S₂O₈. Adapted with permission from , copyright 2019 American Chemical Society; (D) homogenous luminophores GSH-CdTe QDs and DMSA-CdTe QDs sharing the co-reactant H₂O₂. Adapted with permission from , copyright 2021 Elsevier B.V.; and (E) CIS@ZnS NCs emitting at the ultralow potential of 0.30 V and (Ru(bpy)₂(dcbpy))²⁺ as luminophores. Adapted with permission from , copyright 2021 Elsevier B.V.

Figure 7

Schematic of anti-cross-talk multidetection sensors based on spatial-resolved strategy with (A) an ITO electrode with three spatially resolved regions for the detection of three biomarkers. Adapted with permission from , copyright 2017 American Chemical Society; (B) excessive DBAE. Adapted with permission from , copyright 2017 Elsevier B.V.; (C) a novel double working electrode aptamer sensor array on a SPCE. Adapted with permission from , copyright 2015 Elsevier B.V.; and the concentration-controlled strategy with (D) the high concentration of luminol. Adapted with permission from , copyright 2014 American Chemical Society.

Figure 8

Schematic of biosensors with real-time and on-spot detection based on (A) a battery-based microfluidic paper. Adapted with permission from , copyright 2012 Royal Chemistry Society. (B) Automatically toggled switch. Adapted with permission from , copyright 2013 Elsevier B.V.

Figure 9

Schematic of the application of the PRMCECL strategy in (A) MIA by using several self-synthesized concomitant metal complexes with expanded spectral coverage. Adapted with permission from , copyright 2018 American Chemical Society. (B) Immunosensor visualization by regulating the interfacial potential (Δϕa) at the poles of BPE. Adapted with permission from , copyright 2017 American Chemical Society. (C) Ratiometric biosensor based on the PRMCECL nanoluminophore CdSQDs@MOF-5. Adapted with permission from , copyright 2020 American Chemical Society.