Robust and Universal SERS Sensing Platform for Multiplexed Detection of Alzheimer’s Disease Core Biomarkers Using PAapt-AuNPs Conjugates

Multiplexed detection of Alzheimer's disease (AD) core biomarkers is of great significance to early diagnosis and personalized treatment of AD patients. Herein, we construct a robust and convenient surface-enhanced Raman scattering (SERS) biosensing platform for simultaneous detection of Aβ(1-42) oligomers and Tau protein using different Raman dye-coded polyA aptamer-AuNPs (PAapt-AuNPs) conjugates. This strategy relies on the specific protein-aptamer binding-mediated aggregation of AuNPs and the concomitant plasmonic coupling effect that allow us to "turn on" SERS detection of protein biomarkers. To the best of our knowledge, this is the first work in which PAapt-AuNPs conjugates are used for probing protein biomarkers, which may be enlightening for the exploitation of more extensive biological applications of aptamer-AuNPs conjugates. The results reveal that the present strategy displays excellent analytical performance. Moreover, the applicability of this strategy is demonstrated in the artificial cerebrospinal fluid (CSF) samples with satisfactory results. Except for the prominent sensitivity and practicality, our strategy offers additional advantages. The preparation of nanoconjugates is handy and easily repeated, and the synthesis cost is greatly reduced because it dispenses with the complicated labeling process. Moreover, the assay can be accomplished in 15 min, allowing rapid detection of protein biomarkers. Furthermore, simultaneous detection of Tau protein and Aβ(1-42) oligomers is realized by employing different Raman dye-coded nanoconjugates, which is valuable for accurately predicting and diagnosing AD disease. Thus, our PAapt-AuNPs conjugate-based multiplexed SERS strategy indeed creates a useful and universal platform for detecting multiple protein biomarkers and related clinical diagnosis.