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The evolution of optical microscopy from an imaging technique into a tool for materials modification and fabrication is now being repeated with other characterization techniques, including scanning electron microscopy (SEM), focused ion beam (FIB) milling/imaging, and atomic force microscopy (AFM). Fabrication and in situ imaging of materials undergoing a three-dimensional (3D) nano-structuring within a 1−100 nm resolution window is required for future manufacturing of devices. This level of precision is critically in enabling the cross-over between different device platforms (e.g. from electronics to micro-/nano-fluidics and/or photonics) within future devices that will be interfacing with biological and molecular systems in a 3D fashion. Prospective trends in electron, ion, and nano-tip based fabrication techniques are presented.