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; Ying Su; Xiaohan Liang; Kai Cao; Qingming Luo; Haiming Luo

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

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

Authors

Liding Zhang^#^{1

2}, Ying Su^#³, Xiaohan Liang^{1

2}, Kai Cao^{1

2}, Qingming Luo^{4

5}, Haiming Luo^{1

2

5}

Affiliations

¹ Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, 430074 China.
² MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, 430074 China.
³ Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430074 China.
⁴ Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou, 570228 China.
⁵ 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.

^# Contributed equally.

Abstract

Phosphorylation of tau at Ser (396, 404) (p-tau^396,404) is one of the earliest phosphorylation events, and plasma p-tau^396,404 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-tau^396,404 levels. Herein, based on our screening of a pair of p-tau^396,404-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-tau^396,404 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.

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; lateral flow assay; p-tau396,404; plasma detection; surface-enhanced Raman scattering.