Ultrasound-enhanced catalytic hairpin assembly capable of ultrasensitive microRNA biosensing for the early screening of Alzheimer's disease

Catalytic hairpin assembly (CHA) is a promising enzyme-free, isothermal signal amplification strategy, but the relatively time-consuming strand replacement limits its application scenarios. Here, we developed an ultrasoundenhanced catalytic hairpin assembly (UECHA) biosensing platform for early screening of Alzheimer's disease by introducing a portable acoustic-drive platform with functionalized microspheres for effective biomarkers enrichment and fluorescence enhancement. By constructing a gradient ultrasonic field in a microcavity, the platform concentrates the functionalized microspheres in a central position, accompanied by an enhanced fluorescence signal with a specific release. In addition, the programmable frequency modulation can also modify the acoustic potential well and effectively promote non-equilibrium chemical reactions such as CHA (25 min). Compared with the conventional catalytic hairpin assembly (CHA), UECHA allows for direct and quantitative measurement of AD miRNAs down to 3.55 x 10(-15) M in 1 mu L samples. This visual analysis of ultra-trace biomarkers based on acoustic enrichment and promotion provides a new perspective for the rapid and highly sensitive clinical detection of Alzheimer's disease.

Automated summary

Ultrasound-enhanced catalytic hairpin assembly (UECHA) is an enzyme-free, isothermal signal amplification strategy that utilizes a portable acoustic-drive platform with functionalized microspheres to enrich biomarkers and enhance fluorescence. It allows for direct and quantitative measurement of Alzheimer's disease biomarkers, providing a new perspective for early screening.