Selective recognition of the amyloid marker single thioflavin T using DNA origami-based gold nanobipyramid...

The development of effective methods for the detection of protein misfolding is highly beneficial for early stage medical diagnosis and the prevention of many neurodegenerative diseases. Self-assembled plasmonic nanoantennas with precisely tunable nanogaps show extraordinary electromagnetic enhancement, generating extreme signal amplification imperative for the design of ultrasensitive biosensors for point of care applications. Herein, we report the custom arrangement of Au nanobipyramid (Au NBP) monomer and dimer nanoantennas engineered precisely based on the DNA origami technique. Furthermore, we demonstrate the SERS based detection of thioflavin T (ThT), a well-established marker for the detection of amyloid fibril formation, where G-Quadruplexes govern the site-specific attachment of ThT in the plasmonic hotspot. This is the first study for the SERS based detection of the ThT dye attached specifically using a G-Quadruplex complex. The spectroscopic signals of ThT were greatly enhanced due to the designed nanoantennas demonstrating their potential as superior SERS substrates. This study paves the way for boosting the design of next-generation diagnostic tools for the specific and precise detection of various target disease biomarkers using molecular probes.