Atomic Force Microscopy: Applications in the Field of Biology

Abstract

The invention of telescopes and microscopes about 400 years ago revolutionized our perception of the world, extending our sense of seeing. Extending it further and further has since been the driving force for major scientific developments. Local probe techniques extend our sense of touching into the micro- and nanoworld and in this way provide complementary new insight into these worlds we see with microscopic techniques. Furthermore, touching things is an essential prerequisite to manipulating things, and the ability to feel and manipulate single molecules and atoms for sure marks another of these revolutionizing steps in our relation to the world in which we live.

Local probes are small-sized objects, such as the very end of sharp tips, which interact with a sample, or better, the surface of a sample at selected positions. Proximity to or contact with the sample is required to have a high spatial resolution. This, in principle, is an old idea that appeared in the literature from time to time in context with bringing a source of electromagnetic radiation in close contact with a sample (Synge, Philos Mag 6:356, 1928; O’Keefe, J Opt Soc 46:359, 1956; Ash and Nicolls, Nature 237:510, 1972). It found no resonance and therefore was not pursued until the early 1980s. Nanoscale local probes require atomically stable tips and high-precision manipulation devices. The latter are based on mechanical deformations of spring-like structures by piezoelectric, electrostatic, or magnetic forces to ensure continuous and reproducible displacements with precision down to the picometer level. They also require very good vibration isolation. The resolution that can be achieved with local probes is given mainly by the effective probe size, its distance from the sample, and the distance dependence of the interaction between the probes and the sample measured. The last can be considered creating an effective aperture by selecting a small feature of the overall geometry of the probe tip, which then corresponds to the effective probe. One of the great advantages of local probes is that they can work in any environment; this way, they provide the possibility to study live biological processes similar to optical microscopy, but at a resolution similar to electron microscopy (EM).