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Nano Research 2023, 16(5): 7459-7469 https://doi.org/10.1007/s12274-022-5354-4
Research Article | Issue | Published: 28 February 2023

Ultrasensitive and point-of-care detection of plasma phosphorylated tau in Alzheimer’s disease using colorimetric and surface-enhanced Raman scattering dual-readout lateral flow assay

Show Author's Information Liding Zhang1,2,§,  Ying Su3,§,  Xiaohan Liang1,2,  Kai Cao1,2,  Qingming Luo4,5,  Haiming Luo1,2,5( )
Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan 430074, China
MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan 430074, China
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou 570228, China
Research Unit of Multimodal Cross Scale Neural Signal Detection and Imaging, Chinese Academy of Medical Sciences, HUST-Suzhou Institute for Brainsmatics, Jiangsu Industrial Technology Research Institute (JITRI), Suzhou 215123, China

§ Liding Zhang and Ying Su contributed equally to this work.

Keywords:
Alzheimer’s disease, surface-enhanced Raman scattering, lateral flow assay, p-tau396,404, plasma detection
Topics:
Nano deviceNano detection
Cite this article:
Zhang L, Su Y, Liang X, et al. Ultrasensitive and point-of-care detection of plasma phosphorylated tau in Alzheimer’s disease using colorimetric and surface-enhanced Raman scattering dual-readout lateral flow assay. Nano Research, 2023, 16(5): 7459-7469. https://doi.org/10.1007/s12274-022-5354-4
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Abstract Full text Electronic supplementary material About this article

Phosphorylation of tau at Ser (396, 404) (p-tau396,404) is one of the earliest phosphorylation events, and plasma p-tau396,404 level appears to be a potentially promising biomarker of Alzheimer’s disease (AD). The low abundance and easy degradation of p-tau in the plasma make the lateral flow assay (LFA) a suitable choice for point-of-care detection of plasma p-tau396,404 levels. Herein, based on our screening of a pair of p-tau396,404-specific antibodies, we developed a colorimetric and surface-enhanced Raman scattering (SERS) dual-readout LFA for the rapid, highly sensitive, and robust detection of plasma p-tau396,404 levels. This LFA realized a detection limit of 60 pg/mL by the naked eye or 3.8 pg/mL by SERS without cross-reacting with other tau species. More importantly, LFA rapidly and accurately differentiated AD patients from healthy controls, suggesting that it has the potential for clinical point-of-care application in AD diagnosis. This dual-readout LFA has the advantages of simple operation, rapid, and ultra-sensitive detection, providing a new way for early AD diagnosis and intervention, especially in primary and community AD screening.


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Abstract
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Electronic supplementary material
About this article

Ultrasensitive and point-of-care detection of plasma phosphorylated tau in Alzheimer’s disease using colorimetric and surface-enhanced Raman scattering dual-readout lateral flow assay

Show Author's information Liding Zhang1,2,§, Ying Su3,§, Xiaohan Liang1,2, Kai Cao1,2, Qingming Luo4,5, Haiming Luo1,2,5( )
Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan 430074, China
MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan 430074, China
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou 570228, China
Research Unit of Multimodal Cross Scale Neural Signal Detection and Imaging, Chinese Academy of Medical Sciences, HUST-Suzhou Institute for Brainsmatics, Jiangsu Industrial Technology Research Institute (JITRI), Suzhou 215123, China

§ Liding Zhang and Ying Su contributed equally to this work.

Abstract

Phosphorylation of tau at Ser (396, 404) (p-tau396,404) is one of the earliest phosphorylation events, and plasma p-tau396,404 level appears to be a potentially promising biomarker of Alzheimer’s disease (AD). The low abundance and easy degradation of p-tau in the plasma make the lateral flow assay (LFA) a suitable choice for point-of-care detection of plasma p-tau396,404 levels. Herein, based on our screening of a pair of p-tau396,404-specific antibodies, we developed a colorimetric and surface-enhanced Raman scattering (SERS) dual-readout LFA for the rapid, highly sensitive, and robust detection of plasma p-tau396,404 levels. This LFA realized a detection limit of 60 pg/mL by the naked eye or 3.8 pg/mL by SERS without cross-reacting with other tau species. More importantly, LFA rapidly and accurately differentiated AD patients from healthy controls, suggesting that it has the potential for clinical point-of-care application in AD diagnosis. This dual-readout LFA has the advantages of simple operation, rapid, and ultra-sensitive detection, providing a new way for early AD diagnosis and intervention, especially in primary and community AD screening.

Keywords: Alzheimer’s disease, surface-enhanced Raman scattering, lateral flow assay, p-tau396,404, plasma detection

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Publication history
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Acknowledgements

Publication history

Received: 04 September 2022
Revised: 23 November 2022
Accepted: 24 November 2022
Published: 28 February 2023
Issue date: May 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

The authors would like to thank the technical support from Xuewei Du of the China University of Geosciences and Associate Professor Jinyang Zhang of Kunming University of Science and Technology in the screening of monoclonal antibodies. This study was financially supported by the National Science and Technology Innovation 2030 (Nos. 2021ZD0201000 and 2021ZD0201001), the National Natural Science Foundation of China (No. 81971025), and the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (No. 2019-I2M-5-014). We also thank the Optical Bioimaging Core Facility and the Center for Nanoscale Characterization & Devices (CNCD) of WNLO-HUST, the Analytical and Testing Center of HUST, and the Research Core Facilities for Life Science (HUST) for support with data acquisition. We thank all patients and healthy individuals for donating their blood samples.

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