Investigating Analyte Co-Localization at Electromagnetic Gap Hot-Spots For Highly Sensitive (Bio)molecular Detection by Plasmon Enhanced Spectroscopies

Abstract: 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.