Mass spectrometry (MS) is an invaluable tool in chemical analysis with application in areas such as metabolomics, environmental monitoring, and forensics. Traditionally, targeted MS analyses have been employed for analyte detection and quantification, but in recent years the development of non-targeted approaches has become a priority for the community. In a typical non-targeted MS workflow, signals are labelled with, e.g., exact ion mass, isotope patterns, tandem MS fragmentation patterns (i.e., MS n ), and liquid chromatographic retention times (or a subset of these parameters), and analytes are annotated based on matches to a library or agreement with the predictions of a model. For unambiguous assignment, the measured parameters must match those of an internal standard. This approach, of course, is limited by the availability of chemical standards and the chemical coverage of MS libraries. Consequently, novel compounds such as previously uncharacterized natural products and "dark metabolites" typically cannot be identified using these routine approaches. Further to this, the mechanisms of fragmentation (e.g., cyclization, neutral losses) observed via MS n methods are often unclear and it can be challenging to distinguish closely related isomeric species from one another. As a result, traditional mass spectrometric measurements (viz. MS n methods) are often insufficient for complete experimental characterization of molecular structure. This limitation is reflected in the performance of top de novo methods, which identify the correct molecular structure as the best candidate less than 30% of the time. Experimentalists have turned to orthogonal techniques to improve structural elucidation of small molecules. A key challenge in this regard is the separation and isolation of analytes from complex mixtures. For example, traditional benchtop Fourier transform infrared (FT-IR) spectroscopy measures simultaneously the IR spectrum for all components in a mixture, which results in spectra that are the convolution of the components in the mixture, often leading to nondetection of low-abundance species. By coupling MS with infrared ion spectroscopy (IRIS), one can overcome this hurdle by mass-selecting analytes of interest prior to spectroscopic interrogation. Selected ions that absorb IR photons can be internally heated to induce photofragmentation, thereby providing a measurable change in the MS signal. Owing to the sensitivity of the MS detector, this form of action spectroscopy overcomes the limitation of absorption measurements for which the number density of the absorbing analyte must be several orders of magnitude higher than is common in a mass spectrometer. By monitoring ion fragmentation efficiency as a function of IR excitation wavelength, one can generate a vibrational spectrum wherein the vibrational frequencies may be directly related to the molecular structure .