# Development of Cavity-Enhanced Single-Molecule Electronic and Vibrational Spectroscopy for Mechanistic Studies of Biomolecules > **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $308,660 ## Abstract Development of Cavity-Enhanced Single-Molecule Electronic and Vibrational Spectroscopy for Mechanistic Studies of Biomolecules Single-molecule (SM) measurements are a powerful mechanistic tool because they allow multi-step unsynchro- nized dynamics to be directly observed. However, most SM observations rely on fluorescence, which lacks the sensitivity to determine oxidation state, the chemical specificity to elucidate distortion of a particular chemical bond, and requires a fluorescent label. Such information would revolutionize how biochemical mechanisms are determined and could be provided by a method of performing electronic absorption and vibrational spectroscopy on single operational biomolecules. However, surface-enhanced Raman spectroscopy (SERS) is not is suited for probing complex biomolecules, as the method requires intimate contact between the part of the biomolecule to be probed (which may be at the interior), and a metal surface. Similarly, methods exist for performing SM elec- tronic absorption spectroscopy but they lack the required sensitivity or biocompatibility for biomolecules. Thus, a new method is needed to allow SM investigations of in vitro molecular dynamics for mechanistic investigations. We propose the use of optical microcavities as platforms for ultrasensitive SM electronic and vibrational spectroscopy. In one geometry, microcavities are used as highly sensitive thermometers, capable of detecting the heat dissipated by non-fluorescent molecules upon photoexcitation. In this way, non-fluorescent and potentially even weakly absorbing spectral features, such as those diagnostic of the coordination environment of a metal- loenzyme can be elucidated. In a second complimentary geometry we take advantage of the Purcell Effect, which can significantly enhance scattering rates in optical microcavities with small mode volumes and high Quality factors. While SERS requires essentially Van der Waals contact with a plasmonic surface, the microcavity en- hancement can act at a distance of up to ~100 nm from a dielectric surface, making it suitable for probing bio- molecules without significant perturbation. We have now demonstrated the core concepts behind these two strat- egies. In Specific Aims 1-3, we will bring online and evaluate three new microcavity systems that promise to significantly enhance our measurement capacity enough to lay a concrete path to biomedical applications: planar silicon nitride ring resonators (SA 1), fiber Fabry-Perot microcavities (SA 2), and silicon nitride nanobeams (SA3). In all cases we will perform spectroscopy on a series of particles and molecules of increasing challenge, pushing toward the monitoring of a single working metalloenzyme. Supporting calculations suggest that these new resonator geometries will increase our molecular signals by orders of magnitude. Our long-term objective is to bring a new, highly informative, and even disruptive biophysical technique to bear on biological molecules ... ## Key facts - **NIH application ID:** 9943104 - **Project number:** 1R01GM136981-01 - **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON - **Principal Investigator:** Randall H Goldsmith - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $308,660 - **Award type:** 1 - **Project period:** 2020-09-05 → 2024-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9943104 ## Citation > US National Institutes of Health, RePORTER application 9943104, Development of Cavity-Enhanced Single-Molecule Electronic and Vibrational Spectroscopy for Mechanistic Studies of Biomolecules (1R01GM136981-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9943104. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*