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Kuzuya and coworkers developed a versatile sensing system to detect a variety of chemical and biological targets at molecular resolution by using nanomechanical DNA devices [50]. They designed functional nanomechanical DNA origami devices that can be used as “single‐molecule beacons” and function as pinching devices (Figure 1.8a). Using “DNA origami pliers” and “DNA origami forceps,” which consist of two levers ~170 nm long connected at a fulcrum, various single‐molecule targets ranging from metal ions to proteins could be detected by observing a shape transition of the DNA origami devices using AFM (Figure 1.8b). Any detection mechanism suitable for the target of interest, pinching, zipping, or unzipping can be chosen and used orthogonally with differently shaped origami devices in the same mixture using a single platform.