Quantifying the Limits of Detection of Surface-Enhanced Infrared Spectroscopy with Grating Order-Coupled Nanogap Antennas.

Infrared spectroscopy is widely used for biomolecular studies, but struggles when investigating minute quantities of analytes due to the mismatch between vibrational cross sections and IR wavelengths. It is therefore beneficial to enhance absorption signals by confining the infrared light to deeply subwavelength volumes comparable in size to the biomolecules of interest. This can be achieved with surface-enhanced infrared absorption spectroscopy, for which plasmonic nanorod antennas represent the predominant implementation. However, unifying design guidelines for such systems are still lacking. Here, we introduce an experimentally verified framework for designing antenna-based molecular IR spectroscopy sensors. Specifically, we find that in order to maximize the sensing performance, it is essential to combine the signal enhancement originating from nanoscale gaps between the antenna elements with the enhancement obtained from coupling to the grating order modes of the unit cell. Using an optimized grating order-coupled nanogap design, our experiments and numerical simulations show a hotspot limit of detection of two proteins per nanogap. Furthermore, we introduce and analyze additional limit of detection parameters, specifically for deposited surface mass, in-solution concentration, and secondary structure determination. These limits of detection provide valuable reference points for performance metrics of surface-enhanced infrared absorption spectroscopy in practical applications, such as the characterization of biological samples in aqueous solution.