Fabrication of thioflavin-T-modified nanopillared SERS substrates for ultrasensitive beta-amyloid peptide detection

Alzheimer disease (AD) is a major cause of death in the world, and despite intense efforts, there is still no cure for this neurodegenerative disorder. Therefore, early diagnosis of AD is of prime importance, and extensive studies are being conducted to improve the current early detection capabilities and to identify new potential biomarkers for this disease. Here in, we report the fabrication of a novel nanobiosensor platform for the surface-enhanced Raman spectroscopy (SERS)-based ultrasentisitive detection of beta-amyloid (1-42) peptide (A[1-42]), a well-established biomarker of AD. Polymeric films having multibranched nanopillared surfaces (MNS) were first fabricated by drop-casting polycarbonate solutions onto anodized aluminum oxide molds that possess hierarchically branched pores. After peeling from the nanoporous molds, a 20-nm Au coating allowed these MNS substrates to sense sub-picomolar levels of Thioflavin-T (ThT), a SERS-active dye, clinically used to diagnose amyloid plaque presence. Of particular interest, the ThT-modified MNS films demonstrated a gradual ThT SERS signal suppression when incubated with increasing concentrations of A(1-42), and this trend was used to obtain a limit of detection value of 0.5pg/ml and a linear dynamic range between 0.5pg/ml and 100ng/ml. The developed biosensor platform has stable ThT SERS signals for extended periods and displayed promising results in artificial saliva. Ongoing studies are focused on its potential with real body fluids.