The advances in micro- and nanofabrication technologies enable the preparation of increasingly smaller mechanical transducers capable of detecting the forces, motion, mechanical properties and masses that emerge in biomolecular interactions and fundamental biological processes. Thus, biosensors based on nanomechanical systems have gained considerable relevance in the last decade. This review provides insight into the mechanical phenomena that occur in suspended mechanical structures when either biological adsorption or interactions take place on their surface. This review guides the reader through the parameters that change as a consequence of biomolecular adsorption: mass, surface stress, effective Young's modulus and viscoelasticity. The mathematical background needed to correctly interpret the output signals from nanomechanical biosensors is also outlined here. Other practical issues reviewed are the immobilization of biomolecular receptors on the surface of nanomechanical systems and methods to attain that in large arrays of sensors. We then describe some relevant realizations of biosensor devices based on nanomechanical systems that harness some of the mechanical effects cited above. We finally discuss the intrinsic detection limits of the devices and the limitation that arises from non-specific adsorption.

Force curves taken during a load–unload cycle show the presence of a hysteresis loop. The area enclosed by the loop is used to measure the energy dissipated by the tip-sample interaction in tapping-mode scanning force microscopy. The values of the energy loss obtained from force curves are compared with the results derived from a model based on phase shift measurements. The agreement obtained between both methods demonstrates that for the same operating conditions, the higher the phase shift the larger the amount of energy dissipated by the tip-sample interaction. It also confirms the prediction that phase-contrast images can only arise if there are tip-sample inelastic interactions.

The dependence of phase contrast in tapping-mode scanning force microscopy on elastic and inelastic interactions is studied. The cantilever–tip ensemble is simulated as a driven, damped harmonic oscillator. It is found that for tip–sample elastic interactions, phase contrast is independent of the sample’s elastic properties. However, phase contrast associated with elastic modulus variations are observed if viscous damping or adhesion energy hysteresis is considered during tip–sample contact. The phase shift versus tip–sample equilibrium separation was measured for a compliant material (polypropylene) and for a stiff sample (mica). The agreement obtained between theory and experiment supports the conclusions derived from the model. These results emphasize the relevance of energy dissipating processes at the nanometer scale to explain phase contrast imaging in tapping-mode force microscopy.