Lambda bacteriophage deoxyribonucleic acid (DNA) molecules stained with YOYO-I were deposited and stretched on chemically modified Si(I 0 0) wafer and cover glass substrates. The Si(I 0 0) wafer with a natural oxide layer and the cover glass surface were first chemically modified by vapor phase chemisorption with mixed two organosilanes. DNA molecules were then aligned on the substrate surfaces by chemical and physical adsorption from an aqueous solution during molecular combing. The aligned DNA molecules were observed by Kelvin probe force microscopy and intermittent contact-mode atomic force microscopy (AFM) as well as fluorescence microscopy. Interaction between the stretched DNA molecules and the chemically modified Si(1 0 0) substrate surface was examined using these AFMs. (C) 2002 Elsevier Science B.V. All rights reserved.