An interferometric technique that relies on measuring differential displacement between two microcantilevers (a sensing/reference pair) was used to measure the cocaine/aptamer binding induced surface stress changes. Sensing experiments were performed for different concentrations of cocaine from 25 to 500 μM in order to determine the sensor response as a function of cocaine concentration. In the lower concentration range from 25 to 100 μM, surface stress values increased proportionally to coverage of aptamer/cocaine complexes from 11 to 26 mN/m; however, as the cocaine concentration was increased beyond 100 μM, the surface stress values demonstrated a weaker dependence on the affinity complex surface coverage. Based on a sensitivity of 3 mN/m for the surface stress measurement, the lowest detectable threshold for the cocaine concentration was estimated to be 5 μM. Sensing cantilevers could be regenerated and reused because of reversible thermal denaturation of aptamer. 1 figure (publisher abstract modified)