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Spatially multiplexed single-molecule translocations through a nanopore at controlled speeds
S M Leitao1, V Navikas2, H Miljkovic2
1Laboratory for Bio- and Nano-Instrumentation, Institute of Bioengineering, School of Engineering, EPFL, Lausanne, Switzerland.
Nature Nanotechnology
|June 19, 2023
Summary
This study introduces a new method for controlled single-molecule analysis using nanopores. It enhances signal-to-noise ratio for precise detection of molecular structures and features.
Area of Science:
- Nanotechnology
- Biophysics
- Analytical Chemistry
Background:
- Stochastic processes in nanopore sensing limit control over molecule translocation.
- Current label-free single-molecule sensing faces challenges in spatial and temporal control.
Purpose of the Study:
- To develop a method for controlled spatial selection and translocation of single molecules using nanopores.
- To enhance signal-to-noise ratio for improved single-molecule analysis.
Main Methods:
- Utilizing a glass nanopore on a 3D nanopositioner for spatial molecule selection.
- Tethering molecules to a glass surface for controlled translocation.
- Actively controlling nanopore-to-surface distance, scanning velocity, and translocation events.
Main Results:
- Achieved two orders of magnitude increase in signal-to-noise ratio compared to free translocations.
- Demonstrated precise control over molecule scanning and translocation velocity.
- Successfully detected DNA-protein complexes, DNA rulers, and single-nucleotide DNA gaps.
Conclusions:
- The developed method offers unprecedented control over single-molecule nanopore analysis.
- This technique significantly improves the sensitivity and resolution of label-free molecular detection.
- The versatility of the method allows for diverse applications in molecular analysis and diagnostics.
