@article{Fluorescence-Encoded:5274,
      recid = {5274},
      author = {Whaley-Mayda, Lukas},
      title = {Fluorescence-Encoded Infrared Spectroscopy for  Single-Molecule Vibrational Investigation in Solution},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2022-12},
      pages = {437},
      abstract = {Single-molecule methods have revolutionized molecular  science, but techniques possessing the bond-level  structural sensitivity required for chemical problems—e.g.  vibrational spectroscopy—remain difficult to apply in  solution. This thesis describes 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. 

An FEIR instrument is described  that combines design principles of ultrafast IR  spectroscopy with single-molecule fluorescence microscopy  to achieve high detection sensitivity. Specifically, a  trade-off in repetition-rate between the requirements of  efficient fluorescence photon counting and intense,  femtosecond mid-IR pulse generation is satisfied by  employing a 1 MHz Yb fiber laser to pump the experiment,  and the IR pulse delivery is integrated into a confocal  fluorescence microscope configuration. FEIR correlation  spectroscopy, an IR-vibrational analogue of fluorescence  correlation spectroscopy, is introduced to demonstrate  single-molecule sensitivity in solution. Potential  applications of this method as a vibrational probe of  dynamic solution-phase chemical processes are proposed. The  role of FEIR resonance conditions and other practical  experimental factors in achieving single-molecule  sensitivity are discussed through a comparative study of  coumarin fluorophores.

To aid in understanding the  spectroscopic information content of FEIR experiments, a  theoretical description based on fourth-order response  functions for the electronic excited population is  developed. Incorporating the effect of finite pulses and  inter-mode vibrational coherence explains the appearance  and encoding-delay dependence of FEIR signals in our  measurements. Polarization-dependent FEIR experiments that  probe the relative orientation of the vibrational and  electronic transitions, as well as the manifestation of  vibrational relaxation phenomena in FEIR signals, are  discussed.},
      url = {http://knowledge.uchicago.edu/record/5274},
      doi = {https://doi.org/10.6082/uchicago.5274},
}