Method and apparatus which uses harmonic cantilevers, such as used in atomic force microscopy, to detect variations in the attractive and repulsive forces on a solid surface as a result of macromolecular binding, for example, hybridization of a single stranded DNA molecule attached to the surface with another DNA molecule. The complexed macromolecule is less flexible than an uncomplexed molecule. It will typically have more negative charge due to amino acids or DNA monomers. Both stiffness of the surface and the attractive capillary forces will change after binding and may be detected. By scanning the harmonic cantilever across a surface with macromolecules attached in tapping-mode and by recording the signals at the high frequency vibrations provided by harmonic cantilever, complexed molecules on a surface may be identified and quantified.