Integrating terahertz metamaterial and water nanodroplets for ultrasensitive detection of amyloid β aggregates in liquids

The association of amyloid beta (A beta) peptide and its ordered aggregates with the onset of Alzheimer's disease raises the rational use as biomarker for therapeutic and diagnostic. However, due to the heterogeneity among aggregates and relatively low concentration at the physiological conditions, the fast and sensitive detection of the A beta aggregates remains technical challenges. In this work, we develop a label-free method for probing the hydration dynamics of collective A beta aggregates in liquids by using terahertz spectroscopy. A beta aggregates-containing water nanodroplets provide an aqueous confinement environment for improving signal-to-noise ratio of terahertz response. The integration of a metamaterial sensor and nanoconfined droplets further extremely enhances the sensitivity and enables to detect 1 nM A beta aggregates in a buffer solution. This novel development offers a valuable toolkit towards bioanalytical applications in neurobiology but also paves the way for tracing the ultrafast dynamic biological process in fundamental science.

Automated summary

This study introduces a label-free method for probing the hydration dynamics of collective A beta aggregates in liquids using terahertz spectroscopy, by utilizing A beta aggregates-containing water nanodroplets to improve signal-to-noise ratio. The integration of a metamaterial sensor and nanoconfined droplets enhances sensitivity, allowing for the detection of low concentrations of A beta aggregates in buffer solutions. This novel approach provides a valuable toolkit for bioanalytical applications in neurobiology and enables tracing ultrafast dynamic biological processes in fundamental science.