Single-molecule vibrational investigation in solution with fluorescence-encoded infrared spectroscopy

Single-molecule vibrational spectroscopy has enormous potential for investigating chemical phenomena with bond-level structural information. However, established methods rely on near-field signal enhancement mechanisms that require nanometer proximity to a surface or nanostructure, leaving solution-phase problems out of reach. We describe a new approach, fluorescence-encoded infrared (FEIR) spectroscopy, that couples IR-vibrational absorption to a fluorescent electronic transition to achieve high-sensitivity vibrational detection in solution with conventional far-field optics. Our approach uses a double resonance scheme that first excites vibrations by resonant IR absorption, followed by an electronically pre-resonant visible excitation ('encoding') that selectively brings the molecule to its fluorescent excited state. Femtosecond IR and visible pulses are used to make these transitions coincident within the picosecond vibrational lifetime, while splitting the IR pulse into a pulse-pair with an interferometer enables Fourier transform measurements of FEIR vibrational spectra. To demonstrate single-molecule sensitivity in solution, we introduce FEIR correlation spectroscopy—an IR-vibrational analogue of fluorescence correlation spectroscopy—and discuss its potential application as a vibrational probe of dynamic solution-phase chemical processes.