High Resolution Imaging of Immunoglobulin G Antibodies and Other Biomolecules Using Amplitude Modulation Atomic Force Microscopy in Air

The atomic force microscope (AFM) is a very versatile tool for studying biological samples at �nanometre-scale resolution. The resolution one achieves depends on many factors, including the sample properties, the imaging environment, the AFM tip and cantilever probe characteristics, and the signal detection and feedback control mechanism, to name a few. This chapter describes how to routinely achieve the highest possible spatial resolution on isolated protein molecules on mica surfaces. This is illustrated with Immunoglobulin G antibodies but the methods apply equally well to any other globular multi-subunit protein, as well as other biomolecules. Double-stranded DNA is used as a model sample to illustrate the effects of the force regime in amplitude modulation atomic force microscopy (AM AFM) on the image resolution and contrast. AM control is a widely used technique in biological AFM for reasons which are discussed.