Why a diffusing single-molecule can be detected in few minutes by a large capturing bioelectronic interface

Single-molecule detection at a nanometric interface in a femtomolar solution, can take weeks as the encounter rate between the diffusing molecule to be detected and the transducing nano-device is negligibly small. On the other hand, several experiments prove that macroscopic label-free sensors based on field-effect-transistors (FET), engaging micrometric or millimetric detecting interfaces are capable to assay a single-molecule in a large volume within few minutes. The present work demonstrates why at least a single molecule out of a few diffusing in a 100 ul volume has a very high probability to hit a large capturing and detecting electronic interface. To this end, sensing data, measured with an electrolyte-gated FET whose gate is functionalized with 1012 capturing anti-immunoglobulin G, are here provided along with a Brownian diffusion-based modelling. The EG-FET assays solutions down to some tens of zM in concentrations with volumes ranging from 25 ul to 1 ml in which the functionalized gates are incubated for times ranging from 30 s to 20 min.