  Electromagnetic hot-spots at ultra-narrow plasmonic nanogaps carry immense
potential to drive detection limits down to few molecules in sensors based on
surface enhanced Raman or Fluorescence spectroscopies. However, leveraging the
EM hot-spots requires access to the gaps, which in turn depends on the size of
the analyte in relation to gap distances. Herein we leverage a well-calibrated
process based on self-assembly of block copolymer colloids on full-wafer level
to produce high density plasmonic nanopillar arrays exhibiting large number (>
10^10 /cm^2) of uniform inter-pillar EM hot-spots. The approach allows
convenient handles to systematically vary the inter-pillar gap distances down
to sub-10 nm regime. The results show compelling trends of the impact of
analyte dimensions in relation to the gap distances towards their leverage over
inter-pillar hot-spots, and the resulting sensitivity in SERS based molecular
assays. Comparing the detection of labelled proteins in surface-enhanced Raman
and metal-enhanced Fluorescence configurations further reveal the relative
advantage of Fluorescence over Raman detection while encountering the spatial
limitations imposed by the gaps. Quantitative assays with limits of detection
down to picomolar concentrations is realized for both the small organic
molecules and the proteins. The well-defined geometries delivered by
nanofabrication approach is critical to arriving at realistic geometric models
to establish meaningful correlation between structure, optical properties and
sensitivity of nanopillar arrays in plasmonic assays. The findings emphasize
the need for the rational design of EM hot-spots that take into account the
analyte dimensions to drive ultra-high sensitivity in plasmon-enhanced
spectroscopies.
