Enhancing biosensing of trace tau protein in clinical samples via emergence macroscopic directed aggregation

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder that poses a significant risk to human health and well-being. The high cost and invasiveness of neuroimaging and cerebrospinal fluid (CSF) analysis underscores the necessity for accessible early screening via blood samples. In this study, we developed an ultrasound-based strategy for emergent macroscopic that enhances the acoustic response enrichment of specific proteins by introducing functionalized microspheres. This customized macroscopic-directed aggregation method combines protein enrichment with specific fluorescent antibody recognition, enabling quantitative detection characterized by high sensitivity and specificity for tau proteins in clinical samples. In comparison with previously reported biosensing platforms, this strategy achieves indirectly driven clustering of tau proteins by integrating an acoustic resonant chamber, realizing facile and low-cost enrichment detection of protein without the need for amplification. Results demonstrate that this method exhibits a linear detection range from 1 pg/mL to 10 ng/mL, with a detection limit of 0.183 pg/mL. AD patients and healthy individuals were successfully distinguished with an accuracy of 90.9%. This ultrasonic biosensing strategy based on protein aggregation exhibits potential as a valuable tool for early screening of AD.