Detecting Single-Nucleotides by Tunneling Current Measurements at Sub-MHz Temporal Resolution

Area of Science:

• Nanotechnology
• Molecular Biophysics
• Electrochemistry

Background:

• Label-free detection of single molecules is crucial for understanding biological processes.
• Existing methods often require molecular labeling, which can alter native behavior.
• High-resolution electrical measurements offer a promising avenue for label-free analysis.

Purpose of the Study:

• To develop a label-free method for detecting single nucleotides using electrical measurements.
• To investigate the electrical signatures associated with nucleotide interactions at the nanoscale.
• To explore the potential for characterizing dynamic single-molecule conformations.

Main Methods:

• Utilized fast tunneling current measurements at a 1 MHz sampling rate.
• Employed silicon dioxide (SiO₂) protected gold (Au) nanoprobes in a polar solvent.
• Analyzed short current spikes and electrical signature dynamics.

Main Results:

• Observed short current spikes attributed to nucleotide trapping/detrapping between nanoelectrodes.
• Identified signal retardation by capacitance effects with a ~10 microsecond time constant.
• Revealed current fluctuations indicative of molecular conformation degrees of freedom.

Conclusions:

• Demonstrated label-free detection of single nucleotides via tunneling current.
• The method provides insights into dynamic molecular conformations in an electrode gap.
• This technique holds potential for direct characterization of single-molecule dynamics in liquid environments.