Mutation screening based on the mechanical properties of DNA molecules tethered to a solid surface.

We report a rapid gene mutation screening method by making use of the mechanical properties of single-strand DNA (ssDNA) tethered to a solid surface. With proper temperature control, ssDNA in solution undergoes intrabase pairing and forms a specific complex 3D structure. By tethering such ssDNA strands to a solid surface, a DNA film can be formed. The mechanical properties of such DNA films, probed by devices such as a quartz crystal resonator, are directly related to the specific structure of the ssDNA which is characteristic of its base sequence and thus can be used as the basis for mutation screening. Using this approach, we have detected a single base mutation among 545 bases in the P53 gene. This result suggests promising potential of employing the mechanical properties of DNA strands for rapid screening of mutations.