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

Area of Science:

• Biophysics
• Nanotechnology
• Sensor Technology

Background:

• Single-molecule detection is crucial but often slow due to low molecular encounter rates with nanometric interfaces.
• Macroscopic, label-free sensors utilizing field-effect transistors (FETs) show promise for rapid single-molecule detection in larger volumes.

Purpose of the Study:

• To demonstrate the high probability and speed of single-molecule capture at large electronic interfaces.
• To validate a model explaining single-molecule detection governed by Brownian diffusion.

Main Methods:

• Utilized an electrolyte-gated field-effect transistor (EG-FET) with a gate functionalized with anti-immunoglobulin G antibodies.
• Performed sensing assays on solutions with concentrations down to tens of zeptomolar (zM) across various volumes (25 µL to 1 mL).
• Collected experimental data and compared it with Brownian diffusion-based modeling derived from Einstein's diffusion theory.

Main Results:

• Experimental data closely matched the Brownian diffusion model, confirming its predictive power.
• Demonstrated that single molecules diffusing in solution have a high probability of interacting with large-area capturing interfaces.
• Achieved rapid detection within short incubation times (30 s to 20 min).

Conclusions:

• Single-molecule detection at large-area interfaces is primarily controlled by Brownian diffusion.
• This diffusion-controlled process is both highly probable and rapid, enabling fast assays.
• The findings support the use of large-area electronic sensors for efficient single-molecule analysis.