Masataka Murakami (Assoc. Prof.)Masato Ohashi (Assis. Prof.)
Radostin Danev (Assis. Prof.)Masanori Kataoaka (Assis. Prof.)
1. Development of Phase Contrast Electron Microscopy and Biological and Medical Applications
Even for unstained biological specimens images can be highly contrasted in a microscope if equipped with phase plates inserted into the back-focal plane of the objective lens. This microscopic notion was extended to electron microscopy and two contrast methods, Zernike phase contrast and Hilbert differential contrast, have been developed. Examples of phase contrast EM images for biological samples are shown in Figs. 1 to 4.
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2. High Speed DNA Sequencer Based on Electron Microscopy
As an application of phase contrast electron microscopy, a high-throughput base-sequencing method targeting a single DNA molecule has been developed. Figure 5 shows a methodological schematics of the system, which is expected to read one person’s genome per day.
- Y. Kaneko, R. Danev, K. Nitta & K. Nagayama: "In vivo subcellular ultrastructures recognized with Hilbert-differential-contrast transmission electron microscopy." J. Electr. Microsc. 54, 79-84 (2005)
- A. Shimada, H. Niwa, K. Tsujita, S. Suetsugu, K. Nitta, K. Hanawa-Suetsugu, R. Akasaka, Y. Nishino, M. Toyama, L. Chen, Z. J. Liu, B. C. Wang, M. Yamamoto, T. Terada, A. Miyazawa, A. Tanaka, S. Sugano, M. Shirouzu, K. Nagayama, T. Takenawa & S. Yokoyama: "Curved EFC/F-BAR-Domain Dimers Are Joined End to End into a Filament for Membrane Invagination in Endocytosis." Cell, 129, 761-772 (2007)
- R. Danev & K. Nagayama: "Single Particle Analysis Based on Zernike Phase Contrast Microscopy." J. Struct. Biol., 161, 211-218 (2008)
- M. Yamaguchi, R. Danev, K. Nishiyama, K. Sugawara & K. Nagayama: "Zernike phase contrast electron microscopy of ice-embedded influenza A virus." J. Struct. Biol., 162, 271-276 (2008)
- R. Danev, R. Glaeser & K. Nagayama: "Practical factors affecting the performance of a thin-film phase plate for transmission electron microscopy." Ultramicroscopy, doi:10.1016/j.ultramic.2008.12.006 (2008)