Biomedical sensing with the atomic force microscope

In this chapter we highlight the use and advantages of the atomic force microscope (AFMatomic force microscopy (AFM)) in life science. Our aim is to present the wealth of experimental possibilities provided by this powerful toolbox with special regard to biomedical sensing applications. Originally invented in the 1980s to visualize solid surfaces on the nanometer scale, today AFM imaging is routinely used to nondestructively map the surface-ultrastructure of soft biological samples under physiological conditions with unprecedented lateral resolution. Owing to its force detection sensitivity that ranges from nano-Newtons down to a few pico-Newtons, the AFM has become an established technique for exploring kinetic and structural details of inter- and intramolecular interactions and biomolecular recognition processes. The combination of such single-molecule force measurements with topographical imaging has led to the development of recognition imaging, which allows for identification and mapping of specific components in complex biological samples with high spatial accuracy. In the following, the basic principles of biologically relevant AFM imaging modes, as well as the methods of single-molecule force spectroscopy (SMFSsingle-moleculeforce spectroscopy (SMFS)) and simultaneous topography and recognition imaging (TREC) will be introduced and discussed. Selected experiments will be presented in more detail to illustrate the combined application of these techniques in the elucidation of questions in molecular biology, pharmaceutical science and the medical field.