Scanned probe microscopy in biology

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Numerous scanned probe microscopes (SPM) have been developed over the past decade. Most are based on the precise positioning of sample and probe using piezoelectric transducers, and some have the capability of imaging flat surfaces with atomic resolution. The first atomic resolution SPM applied to biological samples was the scanning tunneling microscope (STM). The atomic force microscope (AFM) was subsequently developed and over the past few years has become the instrument of choice for biological applications.Early investigators applied the STM to examinations of organic and biological systems ranging from small molecules to nucleic acids, globular and fibrillar proteins, and larger structures such as viruses, membranes, and even whole cells. Much of this work was done during the mid-80s using electricallyconductive highly-oriented pyrolytic graphite (HOPG) as a substrate. Images were often difficult to obtain and control experiments were lacking. Unfortunately, when careful experiments were undertaken, they revealed that HOPG itself was capable of generating images previously thought to be biological.