Detection of C‐Reactive Protein by Electrochemiluminescence‐Based Droplet‐Free Digital Immunoassay with Tyramide Signal Amplification

C‐reactive protein (CRP) is a widely used biomarker for monitoring inflammatory processes and assessing disease progression in various conditions, including cardiovascular diseases, infections, and autoimmune disorders. In this study, a simplified droplet‐free digital enzyme‐linked immunosorbent ass...

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Main Authors: Hiroya Abe, Shuri Nakamura, Kentaro Ito, Kosuke Ino, Zhengyi Liu, Shinichi Sato, Kumi Y. Inoue, Hitoshi Shiku
Format: Article
Language:English
Published: Wiley-VCH 2025-06-01
Series:ChemElectroChem
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Online Access:https://doi.org/10.1002/celc.202500024
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author Hiroya Abe
Shuri Nakamura
Kentaro Ito
Kosuke Ino
Zhengyi Liu
Shinichi Sato
Kumi Y. Inoue
Hitoshi Shiku
author_facet Hiroya Abe
Shuri Nakamura
Kentaro Ito
Kosuke Ino
Zhengyi Liu
Shinichi Sato
Kumi Y. Inoue
Hitoshi Shiku
author_sort Hiroya Abe
collection DOAJ
description C‐reactive protein (CRP) is a widely used biomarker for monitoring inflammatory processes and assessing disease progression in various conditions, including cardiovascular diseases, infections, and autoimmune disorders. In this study, a simplified droplet‐free digital enzyme‐linked immunosorbent assay (ELISA) system is developed based on electrochemiluminescence (ECL) imaging for the sensitive detection of CRP. This system eliminates the need for droplet or microwell arrays, significantly simplifying the workflow while maintaining high sensitivity. Tyramide signal amplification was employed to enhance signal generation, relying on its localized reaction to achieve precise single‐particle amplification with minimal signal diffusion. The developed assay is capable of detecting poly‐horseradish peroidase at concentrations as low as 1.0 fmol L−1 and successfully adhered to the Poisson distribution model for digital quantification. The application of this system to CRP detection yields a limit of detection of 17.0 pg mL−1 (162 fmol L−1). The ECL bead ratio increases proportionally with CRP concentration, enabling accurate quantification. Moreover, the system exhibits high specificity, showing no response to other biomolecules and maintaining precise detection even in complex biological samples such as human serum. This study highlights the potential of the droplet‐free digital ELISA system for clinical diagnostics and the detection of low‐abundance biomarkers.
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spelling doaj-art-0e8cdba1e77e496fb1bfedc67053e7012025-08-20T02:23:11ZengWiley-VCHChemElectroChem2196-02162025-06-011212n/an/a10.1002/celc.202500024Detection of C‐Reactive Protein by Electrochemiluminescence‐Based Droplet‐Free Digital Immunoassay with Tyramide Signal AmplificationHiroya Abe0Shuri Nakamura1Kentaro Ito2Kosuke Ino3Zhengyi Liu4Shinichi Sato5Kumi Y. Inoue6Hitoshi Shiku7Graduate School of Engineering Tohoku University Sendai Miyagi 980‐8577 JapanGraduate School of Engineering Tohoku University Sendai Miyagi 980‐8577 JapanGraduate School of Environmental Studies Tohoku University Sendai Miyagi 980‐8577 JapanGraduate School of Engineering Tohoku University Sendai Miyagi 980‐8577 JapanFrontier Research Institute for Interdisciplinary Sciences Tohoku University 6‐3 Aoba, Aramaki, Aoba‐ku Sendai Miyagi 980‐8578 JapanFrontier Research Institute for Interdisciplinary Sciences Tohoku University 6‐3 Aoba, Aramaki, Aoba‐ku Sendai Miyagi 980‐8578 JapanGraduate School of Environmental Studies Tohoku University Sendai Miyagi 980‐8577 JapanGraduate School of Engineering Tohoku University Sendai Miyagi 980‐8577 JapanC‐reactive protein (CRP) is a widely used biomarker for monitoring inflammatory processes and assessing disease progression in various conditions, including cardiovascular diseases, infections, and autoimmune disorders. In this study, a simplified droplet‐free digital enzyme‐linked immunosorbent assay (ELISA) system is developed based on electrochemiluminescence (ECL) imaging for the sensitive detection of CRP. This system eliminates the need for droplet or microwell arrays, significantly simplifying the workflow while maintaining high sensitivity. Tyramide signal amplification was employed to enhance signal generation, relying on its localized reaction to achieve precise single‐particle amplification with minimal signal diffusion. The developed assay is capable of detecting poly‐horseradish peroidase at concentrations as low as 1.0 fmol L−1 and successfully adhered to the Poisson distribution model for digital quantification. The application of this system to CRP detection yields a limit of detection of 17.0 pg mL−1 (162 fmol L−1). The ECL bead ratio increases proportionally with CRP concentration, enabling accurate quantification. Moreover, the system exhibits high specificity, showing no response to other biomolecules and maintaining precise detection even in complex biological samples such as human serum. This study highlights the potential of the droplet‐free digital ELISA system for clinical diagnostics and the detection of low‐abundance biomarkers.https://doi.org/10.1002/celc.202500024digital enzyme‐linked immunosorbent assaydigital immunoassaysdroplet‐free digital immunoassayselectrochemiluminescencetyramide signal amplifications
spellingShingle Hiroya Abe
Shuri Nakamura
Kentaro Ito
Kosuke Ino
Zhengyi Liu
Shinichi Sato
Kumi Y. Inoue
Hitoshi Shiku
Detection of C‐Reactive Protein by Electrochemiluminescence‐Based Droplet‐Free Digital Immunoassay with Tyramide Signal Amplification
ChemElectroChem
digital enzyme‐linked immunosorbent assay
digital immunoassays
droplet‐free digital immunoassays
electrochemiluminescence
tyramide signal amplifications
title Detection of C‐Reactive Protein by Electrochemiluminescence‐Based Droplet‐Free Digital Immunoassay with Tyramide Signal Amplification
title_full Detection of C‐Reactive Protein by Electrochemiluminescence‐Based Droplet‐Free Digital Immunoassay with Tyramide Signal Amplification
title_fullStr Detection of C‐Reactive Protein by Electrochemiluminescence‐Based Droplet‐Free Digital Immunoassay with Tyramide Signal Amplification
title_full_unstemmed Detection of C‐Reactive Protein by Electrochemiluminescence‐Based Droplet‐Free Digital Immunoassay with Tyramide Signal Amplification
title_short Detection of C‐Reactive Protein by Electrochemiluminescence‐Based Droplet‐Free Digital Immunoassay with Tyramide Signal Amplification
title_sort detection of c reactive protein by electrochemiluminescence based droplet free digital immunoassay with tyramide signal amplification
topic digital enzyme‐linked immunosorbent assay
digital immunoassays
droplet‐free digital immunoassays
electrochemiluminescence
tyramide signal amplifications
url https://doi.org/10.1002/celc.202500024
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