Single-Molecule Sensitivity in Hot Microcavities in the Unstable Regime

Fiber Fabry-Perot microcavities (FFPCs) enhance light-matter interactions by localizing light in time and space. A new detection scheme exploiting photothermal non-linearities and Pound-Drever-Hall frequency locking enabled label-free detection of solution-phase single biomolecules with unprecedented sensitivity. Here, we deploy a combination of experiment and simulation to provide a quantitative mechanism for the observed single-molecule sensitivity and achieve quantitative agreement with experiment. Key elements of the mechanism include maintaining the FFPC in an unstable regime, allowing it to rapidly shift to hot and cold pho-tothermal equilibria upon perturbation. We show how Brownian molecular trajectories introducing resonance fluctuations less than one thousandth of a linewidth can produce selective and highly amplified responses as long as the perturbations exist in a specific and tunable frequency window termed the molecular velocity filter window. The model’s predictive capacity suggest it will be an im-portant tool to identify new regimes of single-molecule hydrodynamic profiling.