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.

The identification of species is a fundamental problem in analytical chemistry and biology. Mass spectrometers identify species by their molecular mass with extremely high sensitivity (<10⁻²⁴ g). However, its application is usually limited to light analytes (<10⁻¹⁹ g). Here we demonstrate that by using nanomechanical resonators, heavier analytes can be identified by their mass and stiffness. The method is demonstrated with spherical gold nanoparticles and whole intact E. coli bacteria delivered by electrospray ionization to microcantilever resonators placed in low vacuum at 0.1 torr. We develop a theoretical procedure for obtaining the mass, position and stiffness of the analytes arriving the resonator from the adsorption-induced eigenfrequency jumps. These results demonstrate the enormous potential of this technology for identification of large biological complexes near their native conformation, a goal that is beyond the capabilities of conventional mass spectrometers.

Curved thin sheets are ubiquitously found in nature and manmade structures from macro- to nanoscale. Within the framework of classical thin plate theory, the stiffness of thin sheets is independent of its bending state for small deflections. This assumption, however, goes against intuition. Simple experiments with a cantilever sheet made of paper show that the cantilever stiffness largely increases with small amounts of transversal curvature. We here demonstrate by using simple geometric arguments that thin sheets subject to two-dimensional bending necessarily develop internal stresses. The coupling between the internal stresses and the bending moments can increase the stiffness of the plate by several times. We develop a theory that describes the stiffness of curved thin sheets with simple equations in terms of the longitudinal and transversal curvatures. The theory predicts experimental results with a macroscopic cantilever sheet as well as numerical simulations by the finite element method. The results shed new light on plant and insect wing biomechanics and provide an easy route to engineer micro- and nanomechanical structures based on thin materials with extraordinary stiffness tunability.

Microcantilever biosensors in the static operation mode translate molecular recognition into a surface stress signal. Surface stress is derived from the nanomechanical cantilever bending by applying Stoney's equation, derived more than 100 years ago. This equation ignores the clamping effect on the cantilever deformation, which induces significant errors in the quantification of the biosensing response. This leads to discrepancies in the surface stress induced by biomolecular interactions in measurements with cantilevers with different sizes and geometries. So far, more accurate solutions have been precluded by the formidable complexity of the theoretical problem that involves solving the two-dimensional biharmonic equation. In this paper, we present an accurate and simple analytical expression to quantify the response of microcantilever biosensors. The equation exhibits an excellent agreement with finite element simulations and DNA immobilization experiments on gold-coated microcantilevers.

There is an emerging need of nanotools able to quantify the mechanical properties of single biological entities. A promising approach is the measurement of the shifts of the resonant frequencies of ultrathin cantilevers induced by the adsorption of the studied biological systems. Here, we present a detailed theoretical analysis to calculate the resonance frequency shift induced by the mechanical stiffness of viral nanotubes. The model accounts for the high surface-to-volume ratio featured by single biological entities, the shape anisotropy and the interfacial adhesion. The model is applied to the case in which tobacco mosaic virus is randomly delivered to a silicon nitride cantilever. The theoretical framework opens the door to a novel paradigm for biological spectrometry as well as for measuring the Young's modulus of biological systems with minimal strains.