High-speed AFM and nano-visualization of biomolecular processes

Conventional atomic force microscopes (AFMs) take at least 30–60 s to capture an image, while dynamic biomolecular processes occur on a millisecond timescale or less. To narrow this large difference in timescale, various studies have been carried out in the past decade. These efforts have led to a maximum imaging rate of 30–60 ms/frame for a scan range of ~250 nm, with a weak tip–sample interaction force being maintained. Recent imaging studies using high-speed AFM with this capacity have shown that this new microscope can provide straightforward and prompt answers to how and what structural changes progress while individual biomolecules are at work. This article first compares high-speed AFM with its competitor (single-molecule fluorescence microscopy) on various aspects and then describes high-speed AFM instrumentation and imaging studies on biomolecular processes. The article concludes by discussing the future prospects of this cutting-edge microscopy.