The detection of single-molecule fluorescence is a key technique for numerous applications in biomedicines including DNA sequencing, diagnostics, and molecular biology. Unfortunately, the detection volume is limited to femtolitre (10-15) in conventional diffraction-limited optics. In addition, the concentration of molecules has to be limited to pico- or nano-molar, so that on average only one molecule is excited inside the diffraction-limited optical spot. This concentration level is far below the micromolar range where many biologically relevant processes occur. Such a limitation can be overcome by using the so-called zero-mode waveguide (ZMW) where the light field is mainly confined at the bottom of the ZMW, acting as small reaction chambers. The metal film blocks the illuminating light so that only the molecule located at bottom of the ZMW can be excited and detected while leaving other molecules unaffected. The ZMW allows reduction of the observation volume by 3 to 6 orders of magnitude, from 10-15(with a standard confocal microscope) to 10-18 - 10-21 liter, allowing for single-molecule detection. The ZMW structures are commonly fabricated on Al film with light field well confined at bottom but with less field enhancement at visible spectrum compared with that using silver (Ag) or gold (Au). The poor performance for field enhancement further limits the fluorescence emission of a molecule inside these structures according to the optical reciprocity.
We designed a heterogeneous optical slot antenna (OSA) that is capable of detecting single molecule in solutions at high concentrations. The heterogeneous OSA is compose of a rectangular nanoslot fabricated on heterogeneous metallic films that are formed by sequential deposition of gold and aluminum on a glass substrate. The rectangular nanoslot gives rise to large field and fluorescence enhancement for single molecules. The near-field intensity inside a heterogeneous OSA is 170 times larger than that inside an aluminum zero-mode waveguide (ZMW), and the fluorescence emission rate of a molecule inside the heterogeneous OSA is 70 times higher than that of the molecule in free space. The proposed heterogeneous OSA enables excellent balance between performance and cost. The design takes into account the practical experimental conditions so that the parameters chosen in the simulation are well within the reach of current nano-fabrication technologies. Our results can be used as a direct guidance for designing high-performance, low-cost plasmonic nanodevices for the study of bio-molecule and enzyme dynamics at the single-molecule level.