We report the first use of a surface forces apparatus to study the hybridiz
ation of DNA. We study the regime of very high ionic strength (approximate
to1 M) at which commercial DNA chip operations are performed. Using a thiol
end-attached single-stranded oligonucleotide, we find that exposure to the
complementary strand resulted in larger thickness. In addition, the resist
ance to small-amplitude shear deformations when opposed to a nonadsorbing s
urface (mica) increased significantly after hybridization. The thickness at
onset of significant shear resistance was, for single-stranded DNA, consid
erably less than that of hybridized DNA. This could provide a new method to
detect DNA hybridization efficiency.