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 (EF) 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 EF 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.