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Biochem Biophys Res Commun. 2013 Mar 8;432(2):345-9. doi: 10.1016/j.bbrc.2013.01.100. Epub 2013 Feb 8.

Closed-looped in situ nano processing on a culturing cell using an inverted electron beam lithography system.

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Graduate School of Information Science and Technology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.


The beam profile of an electron beam (EB) can be focused onto less than a nanometer spot and scanned over a wide field with extremely high speed sweeping. Thus, EB is employed for nano scale lithography in applied physics research studies and in fabrication of semiconductors. We applied a scanning EB as a control system for a living cell membrane which is representative of large scale complex systems containing nanometer size components. First, we designed the opposed co-axial dual optics containing inverted electron beam lithography (I-EBL) system and a fluorescent optical microscope. This system could provide in situ nano processing for a culturing living cell on a 100-nm-thick SiN nanomembrane, which was placed between the I-EBL and the fluorescent optical microscope. Then we demonstrated the EB-induced chemical direct nano processing for a culturing cell with hundreds of nanometer resolution and visualized real-time images of the scanning spot of the EB-induced luminescent emission and chemical processing using a high sensitive camera mounted on the optical microscope. We concluded that our closed-loop in situ nano processing would be able to provide a nanometer resolution display of virtual molecule environments to study functional changes of bio-molecule systems.

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