Analytical value of detecting an individual molecular binding event: the case of the surface plasmon resonance biosensor.

We explore the ultimate limits of the performance of bioanalytical approaches based on the detection of individual molecular binding events taking place at the sensor surface interfaced with a microfluidic flow-through cell. As a case study, we investigate and compare the bioanalytical performance of flow-through surface plasmon resonance (SPR) sensors based on (1) localized surface plasmons (LSP) which detect a single binding event and (2) propagating surface plasmons (PSP) which integrate a great number of simultaneously occurring binding events. We demonstrate that for the biomolecular interactions most relevant to biosensing the single-binding-event LSP approach is inferior to the integrating PSP approach. We estimate that the number of biorecognition elements available to interact with the analyte molecules would need to be, depending on the size of the analyte and parameters of the molecular interaction, in the order of 10 to 10(3) to increase the probability of the positive response of the LSP-based sensor to that of the PSP-based sensor.