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Updated: Jul 15, 2026

High Resolution Physical Characterization of Single Metallic Nanoparticles
Published on: June 28, 2019
Single-molecule mass spectrometry in solution using a solitary nanopore
Joseph W F Robertson1, Claudio G Rodrigues, Vincent M Stanford
1Electronics and Electrical Engineering Laboratory, Semiconductor Electronics Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8120, USA.
We developed a new mass spectrometry technique using nanopores to analyze molecules in solution. This method distinguishes molecules by their mass, offering real-time characterization of analytes like poly(ethylene glycol).
Area of Science:
- Analytical Chemistry
- Biophysics
- Nanotechnology
Background:
- Traditional mass spectrometry often requires sample ionization and vacuum conditions.
- Characterizing molecules in their native solution state presents significant analytical challenges.
- Nanopore-based sensing offers a label-free approach for analyzing individual molecules.
Purpose of the Study:
- To introduce a novel two-dimensional mass spectrometry method for analyzing analytes in solution.
- To demonstrate the capability of nanopore-analyte interactions for mass-dependent detection.
- To establish a method for real-time molecular characterization.
Main Methods:
- Utilizing a nanometer-scale pore (alpha-hemolysin) to interact with analytes in solution.
- Measuring changes in ionic conductance through the pore as analytes translocate.
- Correlating distinct conductance states and mean residence times with analyte mass.
Main Results:
- Poly(ethylene glycol) molecules entering the nanopore induced distinct, mass-dependent conductance states.
- The technique successfully resolved the repeat unit mass of ethylene glycol.
- A monotonic increase in mean residence time was observed with increasing poly(ethylene glycol) mass.
Conclusions:
- The developed nanopore-based method provides a sensitive, two-dimensional mass spectrometry approach in solution.
- This technique enables real-time, label-free characterization of molecules based on their mass and translocation dynamics.
- The method holds promise for analyzing complex biological and synthetic molecules in their native environments.
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