Label-free, single-molecule biosensing at ultrahigh speeds with metasurface-enhanced coherent Raman scattering - Project Summary Surface-enhanced Raman scattering (SERS) is a popular approach for molecular biosensing, and for a good reason: it enables the identification of molecular targets in a label-free fashion, down to the level of single molecules. This tremendously attractive capability has triggered developments that aim to use SERS for rapid screening of sequences of molecular residues, which would enable applications such as sequencing the nucleobases in DNA. SERS-based sequencing overcomes persistent problems with label-based sequencing methods, including the ability to read out longer sequences and the possibility of directly detecting epigenetic modifications to the nucleobases. Despite successful examples of Raman-based sensing of single molecules, the photophysics of single-molecule SERS measurements on plasmonic substrates limits spectral acquisition rates to the 0.1-10 Hz range, many order of magnitude below the rates needed to render SERS practical for DNA analysis and other biosensing applications where detection speed is of the essence. In this proposal, we overcome the fundamental speed limit in surface-enhanced Raman-based biosensing in particular and label-free single-molecule sensing in general. We achieve label-free detection of single molecules at acquisition rates that are at least 104 faster compared to SERS measurements. Such unprecedented detection speeds are obtained by combining surface-enhanced coherent anti-Stokes Raman scattering (SE-CARS) with the state-of-the-art design of dielectric enhancement structures. Through systematic tailoring of dielectric nano-antennas, and arranging them in a lattice, this project delivers a thermally robust enhancement platform that enables label-free single molecule detection with microsecond signal acquisition times. Our team is comprised of experts in coherent Raman scattering microscopy and advanced engineering of nanophotonic metasurfaces. The proposed work is innovative in that it uniquely fuses the accelerated signal rates of coherent Raman scattering with the latest insights in dielectric nano-antenna design. By pushing the limits of both Raman photophysics and the collective resonances afforded by metasurfaces, our innovation tackles a major obstacle in label-free biosensing and opens up new high- speed applications that have hitherto remained out of reach.
