Provided are methods and systems for high resolution imaging of a material immersed in liquid by scanning probe microscopy. The methods further relate to imaging a material submersed in liquid by tapping mode atomic force microscopy (AFM), wherein the AFM has a microfabricated AFM probe comprising a nanoneedle probe connected to a cantilever beam. The nanoneedle probe is immersed in the liquid, and the rest of the AFM probe, including the cantilever beam to which the nanoneedle probe is attached, remains outside the liquid. The cantilever is oscillated and the nanoneedle probe tip taps the material to image the material immersed in liquid. In an aspect, the material is supported on a shaped substrate to provide a spatially-varying immersion depth with specially defined regions for imaging by any of the methods and systems of the present invention.