Boosting Long-Range Surface-Enhanced Raman Scattering on Plasmonic Nanohole Arrays for Ultrasensitive Detection of...

A fundamental challenge, particularly, in surface-enhanced Raman scattering (SERS) analysis is the detection of analytes that are distant from the sensing surface. To tackle this challenge, we herein report a long-range SERS (LR-SERS) substrate supporting an extension of electric field afforded by long-range surface plasmon resonance (LRSPR) excited in symmetrical dielectric environments. The LR-SERS substrate has a sandwich configuration with a triangle-shaped gold nanohole array embedded between two dielectrics with similar refractive indices (i.e., MgF₂ and water). The finite-difference time-domain simulation was applied to guide the design of the LR-SERS substrate, which was engineered to have a wavelength-matched LRSPR with 785 nm excitation. The simulations predict that the LR-SERS substrate exhibits great SERS enhancement at distances of more than 10 nm beyond its top surface, and the enhancement factor (E_F) has been improved by three orders of magnitude on LR-SERS substrates compared to that on conventional substrates. The experimental results show good agreement with the simulations, an E_F of 4.1 × 10⁵ remains available at 22 nm above the LR-SERS substrate surface. The LR-SERS substrate was further applied as a sensing platform to detect microRNA (miRNA) let-7a coupled with a hybridization chain reaction (HCR) strategy. The developed sensor displays a wide linear range from 10 aM to 1 nM and an ultralow detection limit of 8.5 aM, making it the most sensitive among the current detection strategies for miRNAs based on the SERS-HCR combination to the best of our knowledge.