Patterning Biomolecules using Self-Assembled Monolayer Templates

The emerging biochip requires preferential immobilization of functional biomolecules on nanostructures. Biomolecules have sophisticated functions, such as catalysis, molecular recognition and self-restoration. In order to combine these functions with solid-state devices and realize a novel biomimetic device, the functional biomolecules should be immobilized on an electronic transducer. On the other hand, some functions of a biomolecule can be revealed only by immobilizing the biomolecule on a molecular surgery bed. This novel nanostructure enables us to clarify morphology, kinetics, interaction, and chemistry of the biomolecule of interest. These concepts strongly encourage us to miniaturize the structure to a molecular scale, on which the functional biomolecules are preferentially immobilized.

A self-assembled monolayer (SAM), the thickness of which corresponds to a single standing molecule, is promising as a high-resolution electron beam resist film because the pattern expansion due to the proximity effect is negligible. From the viewpoint of biochip applications, a patterned SAM is also attractive because its surface exhibits various functions according to its end group. It was reported that the silane molecules with long alkyl chains immobilized on the silicon dioxide surface stood side by side, resulting in a self-assembled monolayer of several nanometer in the thickness. The monolayer is prepared by exposing the activated silicon dioxide surface to silane-containing organic solvents or by chemical vapor deposition. The structure of the formed monolayer strongly depends on the deposition process. The SAM is photosensitive to vacuum ultraviolet exposure. There are also several reports on EB lithography performed directly on a silane monolayer in which ozone or hydrofluoric acid is utilized as the developer.

Thus far, we have achieved the smallest and the highest-density nanopattern with sub-10 nm in diameter and 25 nm intervals using a silane SAM as the electron beam-sensitive resist film. By using such a SAM pattern as a template, we have succeeded in site-directed immobilization of deoxyribonucleic acids and proteins, preferential hybridization of deoxyribonucleic acids, and antigen-antibody reactions. The templates are now applied for the quantitative evaluation of adhesion force of cancer cells through the collaborative work involving Waseda University and Research Institute, International Medical Center of Japan (Prof. Yuko Sato's group). The effect of green tea catechin on the proliferation of cancer cells was investigated by using the silane self-assembled monolayer pattern template.


G.-J.Zhang, T.Tanii, T.Funatsu, I.Ohdomari: Patterning of DNA Nanostructures on Silicon Surface by Electron Beam Lithography of Self-Assembled Monolayer, Chem. Commun., 2004 786.

G.-J.Zhang, T.Tanii, T.Zako, T.Hosaka, T.Miyake, Y.Kanari, T.Funatsu, I.Ohdomari: Nanoscale Patterning of Protein Using Electron Beam Lithography of Organosilane Self-Assembled Monolayers, small 1, 2005, 833.

T.Tanii, T.Hosaka, T.Miyake, I.Ohdomari: Electron Beam Lithography on Organosilane Self-Assembled Monolayer Resist, Jpn. J. Appl. Phys. 43, 2004, 4396.

T.Tanii, T.Hosaka, T.Miyake, Y.Kanari, G.-J.Zhang, T.Funatsu, I.Ohdomari: Hybridization of Deoxyribonucleic Acid and Immobilization of Green Fluorescent Protein on Nanostructured Organosilane Templates, Jpn. J. Appl. Phys. 44, 2005, 5851.

M.Tanaka, S.Imai, T.Tanii, Y.Numao, N.Shimamoto, I.Ohdomari, H.Nishide: Nanometer-Sized Polyradical Particles; Organic Magnetic Dot Array Formed on a Silicon Microfabricated Substrate, Journal of Polymer Science A, 2006 521.

T.Miyake, T.Tanii, T.Zako, T.Funatsu, I.Ohdomari: Selectivity Improvement in Protein Nanopatterning with a Hydroxy-Terminated Self-Assembled Monolayer Template, Nanotechnology 18, 2007, 305034.