A scanning electron microscope (SEM) provides real-time imaging with nanometer resolution and a large scanning area, which enables the development and integration of robotic nanomanipulation systems inside a vacuum chamber to realize simultaneous imaging and direct interactions with nanoscaled samples. Emerging techniques for nanorobotic manipulation during SEM imaging enable the characterization of nanomaterials and nanostructures and the prototyping/assembly of nanodevices. This paper presents a comprehensive survey of recent advances in nanorobotic manipulation, including the development of nanomanipulation platforms, tools, changeable toolboxes, sensing units, control strategies, electron beam-induced deposition approaches, automation techniques, and nanomanipulation-enabled applications and discoveries. The limitations of the existing technologies and prospects for new technologies are also discussed.

Mammalian oocytes such as mouse oocytes have a highly elastic outer membrane, zona pellucida (ZP) that cannot be penetrated without significantly deforming the oocyte, even with a sharp micropipette. Piezo drill devices leverage lateral and axial vibration of the micropipette to accomplish ZP penetration with greatly reduced oocyte deformation. However, existing piezo drills all rely on a large lateral micropipette vibration amplitude ( 20 ) and a small axial vibration amplitude (0.1 ). The very large lateral vibration amplitude has been deemed to be necessary for ZP penetration although it also induces larger oocyte deformation and more oocyte damage. This paper reports on a new piezo drill device that uses a flexure guidance mechanism and a systematically designed pulse train with an appropriate base frequency. Both simulation and experimental results demonstrate that a small lateral vibration amplitude (e.g., 2 ) and an axial vibration amplitude as large as 1.2 were achieved. Besides achieving 100% effectiveness in the penetration of mouse oocytes (n = 45), the new piezo device during ZP penetration induced a small oocyte deformation of 3.4 versus larger than 10 using existing piezo drill devices.

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