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. 2023 Feb 28;16(5):7459–7469. doi: 10.1007/s12274-022-5354-4

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

Liding Zhang 1,2,#, Ying Su 3,#, Xiaohan Liang 1,2, Kai Cao 1,2, Qingming Luo 4,5, Haiming Luo 1,2,5,✉
PMCID: PMC9971675  PMID: 37223429

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.

graphic file with name 12274_2022_5354_Fig1_HTML.jpg

Electronic Supplementary Material

Supplementary material (characterization of AuNPs and 4-MBA@AuNP probe; the optimal 4-MBA load for AuNPs; the optimal K2CO3 volumes for 4-MBA@AuNP-3G5 conjugates; the optimal 3G5 load for 4-MBA@AuNP conjugates; effect of NaCl concentration on 4-MBA@AuNP-3G5 stability; the linear curve of T-line color and SERS intensity versus different p-tau396,404 concentrations; the comparison of colorimetric-based LFA test results and the diagnosis results; Raman intensities and antibody activity of 4-MBA@AuNP-3G5 before and after storage; colorimetric intensity of dual-readout LFA detecting different concentrations of p-tau396,404 protein; sequence of synthesized peptides used in this study; information of the participants in this study; the information of antibodies used in this study) is available in the online version of this article at 10.1007/s12274-022-5354-4.

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

Electronic Supplementary Material

12274_2022_5354_MOESM1_ESM.pdf (623.8KB, pdf)

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

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.

Footnotes

Liding Zhang and Ying Su contributed equally to this work.

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Supplementary Materials

12274_2022_5354_MOESM1_ESM.pdf (623.8KB, pdf)

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

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