Single-molecule methods have revolutionized molecular science, but techniques possessing the structural sensitivity required for chemical problems-e.g. vibrational spectroscopy-remain difficult to apply in solution. Here, we describe how coupling infrared-vibrational absorption to a fluorescent electronic transition (fluorescence-encoded infrared (FEIR) spectroscopy) can achieve single-molecule sensitivity in solution with conventional far-field optics. Using the fluorophore Coumarin 6, we illustrate the principles by which FEIR spectroscopy measures vibrational spectra and relaxation and introduce FEIR correlation spectroscopy, a vibrational analogue of fluorescence correlation spectroscopy, to demonstrate single-molecule sensitivity. With further improvements, FEIR spectroscopy could become a powerful tool for single-molecule vibrational investigations in the solution or condensed phase.
