Single-Particle Plasmon Sensing of Discrete Molecular Events: Binding Position versus Signal Variations for Different Sensor Geometries

The sensitivity of a surface plasmon to the dielectric environment makes it a viable tool in detecting single molecules. To be able to precisely determine sensed molecular concentrations and carry out precise analyses of single-molecule binding/unbinding events in real time it is necessary to quantify rigorously the relation between the number of bound molecules and the spectral response of the plasmonic sensor. However, this is challenging as this relation is subject to an uncertainty which is highly dependent on the spatially varying response of the plasmonic nanosensor of choice. The origin of this uncertainty is little understood, and its effect is often disregarded in quantitative sensing experiments. Here, we employ stochastic diffusion-reaction simulations of biomolecular interactions on a sensor's surface combined with electromagnetic calculations of the plasmon resonance peak shift of three metal nanosensors (disk, cone, dimer) to clarify the interplay between position-dependent binding probability and inhomogeneous sensitivity distribution in determining the statistical characteristics of the total signal upon molecular binding. This approach is generally applicable regardless of the specific transduction mechanism at the basis of sensing. Here we identify how this interplay affects the feasibility of using certain plasmonic sensors for sensing low concentrations or real-time monitoring of individual binding reactions and how illumination conditions may affect the level of uncertainty of the measured signal upon molecular binding.