Neuronal tau peptide serves as a key biomarker for neurodegenerative diseases, in specific Alzheimer’s disease, a condition that currently has no cure or definitive diagnosis. The methodology to detect tau levels from non-invasive body fluids remains a major hurdle in rapid and simple diagnostic approach. Thus, developing new detection methods for sensing of tau protein level is crucial. In this work, we report an immunoprobe based on tau antibody (mAb-Tau) conjugated fluorescent gold nanoclusters (AuNCs) quenched with tungsten disulphide nanosheet (WS2 NS) for the detection of tau protein in human serum sample. The mAb-Tau conjugated probe is designed in such a way to provide a specific binding site for tau peptide by strong antigen-antibody interface. The WS2 NS surface quenches the fluorescence of mAb-Tau@AuNCs, which on further, recovered by the addition of tau peptide in a linear concentration range (63.3 - 615.38 pg/mL). The enhancement in fluorescence of WS2 NS @mAb-Tau@AuNCs enables the quantification of tau peptide in concentration pertinent to human serum tau level in Alzheimer’s patients. The developed probe achieves a limit of detection (LOD) and Limit of Quantification (LOQ) of 6.54 pg/mL and 21.8 pg/mL for tau peptide in PBS buffer. The study is further extended in spiked human serum sample with satisfactory recovery percentage in the range of 94.37-117.53% respectively. The technique holds a promise as an immunoprobe for tau peptide detection and foresee its potential in developing an economical viable probe in clinical diagnosis of tau-related neurodegenerative disorders.
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