We demonstrated that it is possible to break apart double-stranded DNA using a thickness shear mode resonator. This procedure measures the force of bond rupture. The measured rupture forces were in the range of 10–40 pN. The procedure was tested experimentally with model complementary and non-complementary oligonucleotides. In the case of the DNA mismatch we observed a signal at a driving voltage of 0.8 V (corresponding to a shear force of 11 pN), while in the case of complementarity the signal at the voltage of 3 V (36 pN) appeared. This procedure may be the ground for the development of new types of biosensors measuring the force of affine interactions (probe/biomolecular target) on the surface of the sensor element.