Reproducible confinement of light on the nanoscale is essential for the ability to observe and control chemical reactions at the single-molecule level. Here we reliably form millions of identical nanocavities and show that the light can be further focused down to the subnanometer scale via the creation of picocavities, single-adatom protrusions with angstrom-level resolution. For the first time, we stabilize and analyze these cavities at room temperatures through high-speed surface-enhanced Raman spectroscopy on specifically selected molecular components, collecting and analyzing more than 2 million spectra. Data obtained on these picocavities allows us to deduce structural information on the nanoscale, showing that thiol binding to gold destabilizes the metal surface to optical irradiation. Nitrile moieties are found to stabilize picocavities by 10-fold against their disappearance, typically surviving for >1 s. Such constructs demonstrate the accessibility of single-molecule chemistry under ambient conditions.

The resonance wavelength of a coupled plasmonic system is extremely sensitive to the distance between its metallic surfaces, resulting in 'plasmon rulers'. We explore this behaviour in the subnm regime using self-assembled monolayers of bis-phthalocyanine molecules in a nanoparticle-onmirror (NPoM) construct. These allow unprecedented sub-angstrom control over spacer thickness via choice of metal centre, in a gap-size regime at the quantum-mechanical limit of plasmonic enhancement. A dramatic shift in the coupled plasmon resonance is observed as the gap size is varied from 0.39 to 0.41 nm. Existing theoretical models are unable to account for the observed spectral tuning, which requires inclusion of the quantum-classical interface, emphasising the need for new treatments of light at the sub-nanoscale.

Plasmonic nanostructures can focus light far below the diffraction limit, and the nearly thousandfold field enhancements obtained routinely enable few- and single-molecule detection. However, for processes happening on the molecular scale to be tracked with any relevant time resolution, the emission strengths need to be well beyond what current plasmonic devices provide. Here, we develop hybrid nanostructures incorporating both refractive and plasmonic optics, by creating SiO2nanospheres fused to plasmonic nanojunctions. Drastic improvements in Raman efficiencies are consistently achieved, with (single-wavelength) emissions reaching 107counts⋅mW−1⋅s−1and 5 × 105counts∙mW−1∙s−1∙molecule−1, for enhancement factors >1011. We demonstrate that such high efficiencies indeed enable tracking of single gold atoms and molecules with 17-µs time resolution, more than a thousandfold improvement over conventional high-performance plasmonic devices. Moreover, the obtained (integrated) megahertz count rates rival (even exceed) those of luminescent sources such as single-dye molecules and quantum dots, without bleaching or blinking.

Quantitative applications of surface-enhanced Raman spectroscopy (SERS) often rely on surface partition layers grafted to SERS substrates to collect and trap-solvated analytes that would not otherwise adsorb onto metals. Such binding layers drastically broaden the scope of analytes that can be probed. However, excess binding sites introduced by this partition layer also trap analytes outside the plasmonic “hotspots”. We show that by eliminating these binding sites, limits of detection (LODs) can effectively be lowered by more than an order of magnitude. We highlight the effectiveness of this approach by demonstrating quantitative detection of controlled drugs down to subnanomolar concentrations in aqueous media. Such LODs are low enough to screen, for example, urine at clinically relevant levels. These findings provide unique insights into the binding behavior of analytes, which are essential when designing high-performance SERS substrates.

Metal/organic-molecule interactions underpin many key chemistries but occur on sub-nm scales where nanoscale visualisation techniques tend to average over heterogeneous distributions. Single molecule imaging techniques at the atomic scale have found it challenging to track chemical behaviour under ambient conditions. Surface-enhanced Raman spectroscopy can optically monitor the vibrations of single molecules but understanding is limited by the complexity of spectra and mismatch between theory and experiment. We demonstrate that spectra from an optically generated metallic adatom near a molecule of interest can be inverted into dynamic sub-Å metal-molecule interactions using a comprehensive model, revealing anomalous diffusion of a single atom. Transient metal-organic coordination bonds chemically perturb molecular functional groups > 10 bonds away. With continuous improvements in computational methods for modelling large and complex molecular systems, this technique will become increasingly applicable to accurately tracking more complex chemistries.