Overview of Gas-Generating-Reaction-Based Immunoassays

Abstract

Point-of-care (POC) immunoassays have become convincing alternatives to traditional immunosensing methods for the sensitive and real-time detection of targets. Immunoassays based on gas-generating reactions were recently developed and have been used in various fields due to their advantages, such as rapid measurement, direct reading, simple operation, and low cost. Enzymes or nanoparticles modified with antibodies can effectively catalyze gas-generating reactions and convert immunorecognition events into gas pressure signals, which can be easily recorded by multifunctional portable devices. This article summarizes the advances in gas-generating-reaction-based immunoassays, according to different types of signal output systems, including distance-based readout, pressure differential, visualized detection, and thermal measurement. The review mainly focuses on the role of photothermal materials and the working principle of immunoassays. In addition, the challenges and prospects for the future development of gas-generating-reaction-based immunoassays are briefly discussed.

Keywords: gas generating; immunoassays; nanozymes; point-of-care testing; pressure.

Figure 7

(A) Schematic illustration of a PtNP-based POC immunoassay based on paper electrode-based flexible pressure sensor and digital multimeter [107]. Copyright 2019 American Chemical Society. (B) Schematic illustration of a AuNP-labeled pressure immunoassay using a Pt staining method to stain AuNPs with a Pt shell [109]. Copyright 2018 American Chemical Society. (C) Schematic illustration of a pressure immunoassay for Salmonella detection using PtNP-loaded MnO₂ nanoflowers and a thin-film pressure detector [112]. Copyright 2020 Elsevier.

Figure 8

(A) Schematic illustration of a multifunctional Nb₂C MXene-based photothermal-enhanced pressure immunoassay for the portable detection of IL-6 [116]. Copyright 2023 Elsevier. (B) Schematic illustration of an enhanced pressure-based immunoassay based on the PtNP-catalyzed chromogenic reaction between H₂O₂ and TMB [117]. Copyright 2021 American Chemical Society.

Figure 1

(A) Working principle of the V-chip [48]. Copyright 2012 Springer Nature. (a) Schematic view of a typical V-chip. On the left is a view of an assembled V-chip with the flow path at the horizontal position. Ink and H₂O₂ can be preloaded, and the ELISA assay can be performed in the designated lanes. An oblique slide breaks the flow path and forms the structure on the right, causing catalase and H₂O₂ to react and push the inked bars. (b) V-chip ELISA reaction scheme and the oxygen generation mechanism. (c) Image of 50 sample wells loaded with different-colored food dyes using swab tips. Scale bar, 0.5 cm. (B) Schematic illustration of a competitive V-chip with real-time internal control for the detection of hCG based on generation of N₂ gas [50]. Copyright 2015 American Chemical Society.

Figure 2

(A) Schematic illustration of a V-chip and PtNP-based immunoassay for the visual detection of EVs using a bacteria-proliferation-based cascade amplification strategy [67]. Copyright 2024 Elsevier. (B) Schematic illustration of a photothermal bar-chart microfluidic chip for the visual detection of PSA based on nanomaterial-mediated photothermal effects [69].

Figure 3

(A) Schematic illustration of an POC immunosensor for TnI detection based on dendritic PtNPs and capillary tube indicators [70]. Copyright 2015 American Chemical Society. (B) Schematic illustration of a capillary-based immunosensor for PSA detection using Pt@AuNPs as catalytic labels [71]. Copyright 2016 Elsevier. (C) Schematic illustration of a pressure immunosensor for the determination of E. coli in water using catalase-modified, AuNP-loaded polystyrene nanospheres [72]. Copyright 2020 Elsevier. (D) Schematic illustration of a pressure-based immunoassay for CEA detection based on the photothermal effect of oxTMB and the fluorescence quenching of perovskite [73]. Copyright 2022 American Chemical Society.

Figure 4

(A) Schematic illustration of a POCT immunoassay for the detection of foodborne pathogenic bacteria using MnO₂ nanoflowers as labels and a disposable medical infusion extension line as readout [76]. Copyright 2019 Elsevier. (B) Schematic illustration of a dual-mode pressure immunosensor for the detection of aminopyrine based on color distance change and electrochemical signal [77]. Copyright 2023 American Chemical Society. (C) Schematic illustration of a foam-based immunoassay for the detection of E. coli O157:H7 using Au@Pt/SiO₂ NPs [78]. Copyright 2019 Elsevier. (D) Schematic illustration of an unplugged foam-based immunochromatographic assay for E. coli O157:H7 detection using Au@PtNPs [79]. Copyright 2020 Elsevier.

Figure 5

(A) Schematic illustration of a Au@Pt core/shell NP-based immunosensor for the detection of CEA and ractopamine with a barometer as readout [96]. Copyright 2017 American Chemical Society. (B) Schematic illustration of a competitive-type pressure immunosensor for DAS detection based on Au@PtNPs [97]. Copyright 2019 American Chemical Society.

Figure 6

Schematic illustration of a pressure/colorimetric dual-readout ITS for the detection of AFB₁ [100]. Copyright 2021 Elsevier.

Figure 9

(A) Schematic illustration of a PtNP-based pressure immunosensor for the visual detection of CEA combining with a flexible pressure sensor and an electrochromic device [118]. Copyright 2021 American Chemical Society. (B) Schematic illustration of a multipixel dual-channel pressure sensor array for CEA detection with the visual sensing ability of full-color switching and electrical signals [119]. Copyright 2022 American Chemical Society.

Figure 10

(A) Schematic illustration of a flexible sensing platform using Pt/Zn-TCPP nanozyme for dual-mode pressure and the temperature detection of CEA [120]. Copyright 2024 American Chemical Society. (B) Schematic illustration of a pressure-colorimetric multisignal immunoassay based on photothermal-activated multiple rolling signal amplification for HE4 detection [122]. Copyright 2023 Elsevier.

Figure 11

(A) Schematic illustration of a thermal immunosensor using a simple thermometer as readout by combing the gas-generating reaction with the exothermic reaction between H₂O and CaO [21]. Copyright 2019 American Chemical Society. (B) Schematic illustration of an immunoassay for Salmonella detection based on PtNP-loaded Fe-MOFs as catalysts and the combination of the gas-generating reaction with the exothermic reaction [123]. Copyright 2021 American Chemical Society.