The general features of tapping mode operation of a scanning force microscope are presented. Relevant factors of tapping mode such as forces, deformation, and contact times can be calculated as functions of tapping frequency, amplitude damping, and sample elastic and viscoelastic properties. Typical contact times per oscillation are about 10-7 s for hard samples and 6 × 10-7 s for soft materials, i.e., between one and two orders of magnitude smaller than their equivalents in contact mode force microscopy. The model proposed allows the determination of the phase lag between excitation signal and cantilever response. Major factors to phase contrast are viscoelastic properties and adhesion forces with little participation from elastic properties. Experiments performed on droplets of glycerin deposited on graphite illustrate the ability to image them by recording phase changes.

One-dimensional nanomechanical resonators based on nanowires and nanotubes have emerged as promising candidates for mass sensors. When the resonator is clamped at one end and the atoms or molecules being measured land on the other end (which is free to vibrate), the resonance frequency of the device decreases by an amount that is proportional to the mass of the atoms or molecules. However, atoms and molecules can land at any position along the resonator, and many biomolecules have sizes that are comparable to the size of the resonator, so the relationship between the added mass and the frequency shift breaks down. Moreover, whereas resonators fabricated by top-down methods tend to vibrate in just one dimension because they are usually shaped like diving boards, perfectly axisymmetric one-dimensional nanoresonators can support flexural vibrations with the same amplitude and frequency in two dimensions. Here, we propose a new approach to mass sensing and stiffness spectroscopy based on the fact that the nanoresonator will enter a superposition state of two orthogonal vibrations with different frequencies when this symmetry is broken. Measuring these frequencies allows the mass, stiffness and azimuthal arrival direction of the adsorbate to be determined.

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 advances in micro-and nanofabrication technologies are enabling 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 bioreceptor molecules on the surface of nanomechanical sensors and methods to attain that in large arrays of sensors. We describe then 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.2

The properties of water at the nanoscale are crucial in many areas of biology, but the confinement of water molecules in sub-nanometre channels in biological systems has received relatively little attention. Advances in nanotechnology make it possible to explore the role played by water molecules in living systems, potentially leading to the development of ultrasensitive biosensors. Here we show that the adsorption of water by a self-assembled monolayer of single-stranded DNA on a silicon microcantilever can be detected by measuring how the tension in the monolayer changes as a result of hydration. Our approach relies on the microcantilever bending by an amount that depends on the tension in the monolayer. In particular, we find that the tension changes dramatically when the monolayer interacts with either complementary or single mismatched single-stranded DNA targets. Our results suggest that the tension is mainly governed by hydration forces in the channels between the DNA molecules and could lead to the development of a label-free DNA biosensor that can detect single mutations. The technique provides sensitivity in the femtomolar range that is at least two orders of magnitude better than that obtained previously with label-free nanomechanical biosensors and with label-dependent microarrays.