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Why a Diffusing Single‐Molecule can be Detected in Few Minutes by a Large Capturing Bioelectronic Interface
Why a Diffusing Single‐Molecule can be Detected in Few Minutes by a Large Capturing Bioelectronic Interface
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Why a Diffusing Single‐Molecule can be Detected in Few Minutes by a Large Capturing Bioelectronic Interface
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Why a Diffusing Single‐Molecule can be Detected in Few Minutes by a Large Capturing Bioelectronic Interface
Why a Diffusing Single‐Molecule can be Detected in Few Minutes by a Large Capturing Bioelectronic Interface
Journal Article

Why a Diffusing Single‐Molecule can be Detected in Few Minutes by a Large Capturing Bioelectronic Interface

2022
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Overview
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 nanodevice is negligibly small. On the other hand, several experiments prove that macroscopic label‐free sensors based on field‐effect‐transistors, 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 µL volume has a 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 modeling. The EG‐FET assays solutions down to some tens of zM in concentrations with volumes ranging from 25 µL to 1 mL in which the functionalized gates are incubated for times ranging from 30 s to 20 min. The high level of accordance between the experimental data and a model based on the Einstein's diffusion‐theory proves how the single‐molecule detection process at large‐capturing interfaces is controlled by Brownian diffusion and yet is highly probable and fast. A single‐molecule out of few in 100 µL diffusing according to Einstein's theory, can impinge on a large‐area (0.2 cm2) gate within 10 min. This is demonstrated by modeling the data gathered with a bioelectronic platform whose gate is functionalized with a highly packed layer of capturing‐antibodies. A general equation reproduces the data measured at different incubation volume and times.