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The combination of AFM with conventional techniques, as well as AFM itself, allows answering biomedical questions of high interest. We could show this clearly for CFTR with single molecule imaging and observation of structural dynamics in native cell membranes. AFM also allows identification and determination of CFTR at single molecule level. The observation that the lack of CFTR influences the mechanical and, therefore, rheological properties of RBC could lead to a novel therapeutic approach for CF treatment. Regarding the fact that the defect of a single protein causes lethal diseases, research at the single molecule level would become vital in the future.

In this review, we have presented scanning probe microscopy across dimensions from large samples like single cells, via single biomolecules and nanometer small ion induced defects on crystal surfaces to subatomic features like electronic orbitals and single electron spins.

Scanning probe microscopy is on its way to a standard laboratory method: subatomic features can be imaged, and with magnetic resonance force microscopy it has even left the two-dimensional surface regime. Perhaps in the not too distant future 3D-imaging of (complex) molecules, at surfaces or in the bulk state, with atomic resolution might become possible with these powerful techniques. The 3-D MRFM would also deliver chemical specific information because each magnetic nucleus has a unique gyromagnetic ratio.

In this review, we have presented scanning probe microscopy across dimensions from large samples like single cells, via single biomolecules and nanometer small ion induced defects on crystal surfaces to subatomic features like electronic orbitals and single electron spins.

Scanning probe microscopy is on its way to a standard laboratory method: subatomic features can be imaged, and with magnetic resonance force microscopy it has even left the two-dimensional surface regime. Perhaps in the not too distant future 3D-imaging of (complex) molecules, at surfaces or in the bulk state, with atomic resolution might become possible with these powerful techniques. The 3-D MRFM would also deliver chemical specific information because each magnetic nucleus has a unique gyromagnetic ratio.

In conclusion, we have shown how scanning probe microscopy has been applied to investigate, isolate and manipulate different organic molecules on metal, semiconductor and insulating surfaces. The same chemical compounds give rise to different structures, depending on several factors, such as the adsorbate coverage, the substrate orientation or the temperature. Self-assembled patterns formed on the step edges of insulating surfaces — or raised from metal substrates by specifically designed molecular “legs” — can be used as molecular wires. The different conformations assumed by single molecules can be viewed as different logical states of a digital circuit. Scanning probe microscopy might become one of the essential ingredients to design future molecular electronics devices. Well-defined experiments to investigate self-assembly characteristics and to measure the mechanical and electrical properties of the individual molecules will be performed. Internal degrees of freedoms of the molecules and mechanical instabilities are rather complex phenomena, which will need both experimental and computational efforts to achieve the required degree of control of these novel molecular electronics devices.

The review on low-dimensional systems reported provides just a little taste of the expanding field of nanoscale materials and structures. Many works are showing that qualitatively new behavior in the physical phenomena is often produced by the size constraints. Although such changes in behavior can be the dominant effects in nanoscale structures, we still have remarkably little experience or intuition for the expected phenomena and their practical implication.

As surface scientists, we realize that we are just uncovering a wide world of physical phenomena involving complex systems spanning from physics to chemistry and biology. In particular, the study of simplicity will give way to the study of complexity as the unifying theme. In this world, simple structures interact to create new phenomena and assemble themselves into devices, or complicated structures can be designed atom by atom for desired characteristics.

We hope that the few examples reported here will stimulate researchers to engage in the exploration of this exciting world.

We would like to thank Mattia Fanetti, Maria Grazia Betti, Carlo Mariani and Cinzia Cepek as collaborators for the results we presented here. The nanospectroscopy facility in Brescia was funded by INFM under the Strumentazione Avanzata program. The research work presented here was funded by FIRB-MIUR project “Carbon-based micro and nanostructures”, by PRIN-MIUR project “Nanotribology”, and by the CARIPLO Foundation.

In this review, we have presented scanning probe microscopy across dimensions from large samples like single cells, via single biomolecules and nanometer small ion induced defects on crystal surfaces to subatomic features like electronic orbitals and single electron spins.

Scanning probe microscopy is on its way to a standard laboratory method: subatomic features can be imaged, and with magnetic resonance force microscopy it has even left the two-dimensional surface regime. Perhaps in the not too distant future 3D-imaging of (complex) molecules, at surfaces or in the bulk state, with atomic resolution might become possible with these powerful techniques. The 3-D MRFM would also deliver chemical specific information because each magnetic nucleus has a unique gyromagnetic ratio.

The most striking and impressive feature of AFM is probably related to its flexibility, with particular emphasis on detailed morphological, contact mechanics, friction and adhesion studies routinely performed under different environments. These capabilities have led the AFM to extend our fundamental knowledge on friction phenomena.

Considerable progress has been made on friction laws and it appears well-established that the phenomenological Amontons—Dejaguin equation can safely be extended down to the nanoscale, describing both single-asperity and multi-asperity contacts. Therefore, a new challenging subject regards the characterization of the shear stress τ and its dependence on the physically relevant dissipation channels and sliding parameters. On the theoretical side, models have been developed treating the role of multiscale surface roughness, thus it is now possible to predict some of the most significant properties of solid bodies in contact.

At present, there is a strong trend towards a transition from macro to micro and nanoscale that may give a new insight into the basic problems of tribology, such as the influence of deformation and adhesion mechanisms on friction and wear.

The atomic force microscope provides a unique opportunity to obtain the 3D surface topography at nanoscale, to simulate the contact interaction of rough surfaces, to measure the micro-mechanical properties of materials in the thin surface layers, and to model the elementary acts of wear. AFM can be efficiently used in the development ofmultilevel models of surface roughness and contact simulation based on these models.

There are certain drawbacks of AFM related to the dynamics of probe-to-surface interaction and effects of probe shape and hardness on the test data. These drawbacks can be overcome by using precise quasi-static devices and microtribometers in combination with AFM.

It is clear that progress in engineering will provide a lot of new fields in applications of AFM, but micro- and nanotribology continue to be fascinating and fruitful areas for such applications.