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

TL;DR

This paper explains why large bioelectronic interfaces can detect single molecules quickly in large solutions, combining experimental data with diffusion modeling to show high hit probabilities.

Contribution

It demonstrates the high likelihood of molecule capture at large bioelectronic interfaces, supported by experimental data and Brownian diffusion modeling.

Findings

Large interfaces increase molecule hit probability

Detection in large volumes occurs within minutes

Experimental data supports diffusion-based model

Abstract

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.