The most lacking information of biological macromolecules is their dynamic behavior in action. AFM has a potential to acquire this information because it allows high-resolution imaging of biological macromolecules in physiological solutions. To materialize this potential, the high-speed scan ability has to be attained. The scan speed is governed by two factors; the feedback bandwidth and the scannerfs bandwidth (i.e., the maximum scan-frequency at which the scanner does not produce unwanted vibrations). In the feedback loop, various devices are contained such as cantilever, sensor, amplitude detector, feedback circuit, and scanner. Hence, all of these devices have to be optimized for high-speed scanning. In addition, to visualize biological processes, weak tip-sample interaction is required. However, this requirement is difficult to be reconciled with high-speed scanning. In the past few years, various devices and techniques have been developed to increase the scan speed as well as to reduce the tip-sample interaction1-6. By these efforts, video-rate AFM imaging under feedback operation has been realized, and dynamic behaviors of some biological processes have been captured on video, such as hand-over-hand movement of myosin V along actin filaments and GroEL-GroES interaction in a negatively cooperative manner. Thus, a dream in life science that had been longed for has been realized to some extent. A task to be solved in the next step is to reduce the tip-sample interaction more extensively without degrading the scan speed, so that even dynamic behavior of membrane proteins on a live cell can be visualized. In this talk, I review recent progress of high-speed AFM and describe a possibility of high-speed non-contact AFM.
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