Preferential immobilization of biomolecules on silicon microstructure array by means of electron beam lithography on organosilane self-assembled monolayer resist

A novel fabrication process of silicon microstructure array for preferential immobilization of biomolecules is proposed. We perform electron beam lithography on a self-assembled monolayer (SAM), and achieve high-density silicon patterns terminated with both 3-aminopropyltriethoxysilane (APTES) and octadecyltrimethoxysilane (ODS). The amino-terminated surface produces the site-directed covalent immobilization of DNA inside the pattern, while the hydrophobic surface of the ODSSAM prevents the adsorption. As a result, we have succeeded in immobilizing the DNA within the amino-modified area. By using this methodology, we demonstrate the miniaturization of deoxyribonucleic acid (DNA) chip. After the covalent attachment of the amino-modified oligonucleotides to the microstructures, we hybridize the immobilized DNAwith the target DNA labeled with a fluorescent dye. The signals from the DNA chip exhibit the specific binding due to the DNA–DNA interaction. These results show the feasibility of this technique for high-density information storage and biochip miniaturization. # 2004 Elsevier B.V. All rights reserved.