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Title: A novel low energy electron microscope for DNA sequencing and surface analysis

Monochromatic, aberration-corrected, dual-beam low energy electron microscopy (MAD-LEEM) is a novel technique that is directed towards imaging nanostructures and surfaces with sub-nanometer resolution. The technique combines a monochromator, a mirror aberration corrector, an energy filter, and dual beam illumination in a single instrument. The monochromator reduces the energy spread of the illuminating electron beam, which significantly improves spectroscopic and spatial resolution. Simulation results predict that the novel aberration corrector design will eliminate the second rank chromatic and third and fifth order spherical aberrations, thereby improving the resolution into the sub-nanometer regime at landing energies as low as one hundred electron-Volts. The energy filter produces a beam that can extract detailed information about the chemical composition and local electronic states of non-periodic objects such as nanoparticles, interfaces, defects, and macromolecules. The dual flood illumination eliminates charging effects that are generated when a conventional LEEM is used to image insulating specimens. A potential application for MAD-LEEM is in DNA sequencing, which requires high resolution to distinguish the individual bases and high speed to reduce the cost. The MAD-LEEM approach images the DNA with low electron impact energies, which provides nucleobase contrast mechanisms without organometallic labels. Furthermore, the micron-size field of view whenmore » combined with imaging on the fly provides long read lengths, thereby reducing the demand on assembling the sequence. Finally, experimental results from bulk specimens with immobilized single-base oligonucleotides demonstrate that base specific contrast is available with reflected, photo-emitted, and Auger electrons. Image contrast simulations of model rectangular features mimicking the individual nucleotides in a DNA strand have been developed to translate measurements of contrast on bulk DNA to the detectability of individual DNA bases in a sequence.« less
 [1] ;  [1] ;  [2] ;  [3] ;  [4] ;  [2]
  1. Electron Optica Inc., Palo Alto, CA (United States)
  2. Stanford Univ. School of Medicine, Palo Alto, CA (United States)
  3. Electron Optica Inc., Palo Alto, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
OSTI Identifier:
Grant/Contract Number:
AC02-05CH11231; R43HG006303
Accepted Manuscript
Journal Name:
Additional Journal Information:
Journal Volume: 145; Journal ID: ISSN 0304-3991
Research Org:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
47 OTHER INSTRUMENTATION Low energy electron microscopy; Monochromator; Aberration correction; Dual beam illumination; Energy filtering; DNA Sequencing; Contrast