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Updated: May 3, 2026

Nanopore DNA Sequencing for Metagenomic Soil Analysis
Published on: December 14, 2017
A novel low energy electron microscope for DNA sequencing and surface analysis.
M Mankos1, K Shadman1, H H J Persson2
1Electron Optica Inc., 1000 Elwell Court ♯110, Palo Alto, CA 94303, USA.
Monochromatic, aberration-corrected, dual-beam low energy electron microscopy (MAD-LEEM) offers sub-nanometer imaging resolution for nanostructures. This novel technique shows promise for high-speed DNA sequencing by imaging nucleobases without labels.
Area of Science:
- Surface Science and Nanotechnology
- Electron Microscopy and Spectroscopy
- Biophysics and Genomics
Background:
- Conventional low-energy electron microscopy (LEEM) faces limitations in resolution and charging effects when imaging insulating specimens.
- Existing techniques struggle to provide high-resolution, label-free imaging of biological macromolecules like DNA.
- Sub-nanometer resolution is crucial for applications such as DNA sequencing, requiring precise identification of individual bases.
Purpose of the Study:
- To introduce and characterize a novel Monochromatic, Aberration-corrected, Dual-beam Low Energy Electron Microscopy (MAD-LEEM) instrument.
- To demonstrate the capability of MAD-LEEM for high-resolution imaging of nanostructures and surfaces.
- To explore the potential of MAD-LEEM for label-free DNA sequencing by achieving base-specific contrast.
Main Methods:
- Integration of a monochromator, mirror aberration corrector, energy filter, and dual flood illumination into a single LEEM instrument.
- Utilizing low electron landing energies (as low as 100 eV) to minimize sample damage and enhance contrast.
- Developing image contrast simulations to correlate experimental measurements with the detectability of individual DNA bases.
Main Results:
- The MAD-LEEM design predicts the elimination of chromatic and spherical aberrations, enabling sub-nanometer spatial resolution.
- Dual beam illumination effectively suppresses charging effects on insulating specimens.
- Experimental results show base-specific contrast using reflected, photo-emitted, and Auger electrons from immobilized oligonucleotides.
Conclusions:
- MAD-LEEM is a powerful new technique for high-resolution imaging of nanostructures and surfaces.
- The instrument's capabilities, including dual beam illumination and aberration correction, overcome limitations of conventional LEEM.
- MAD-LEEM presents a promising avenue for high-speed, label-free DNA sequencing with potential for reduced costs.
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