Label-free ultra-sensitive visualization of structure below the diffraction resolution limit

For both fundamental study of biological processes and early diagnosis of diseases, information about nanoscale changes in tissue and cell structure is crucial. Nowadays, almost all currently known nanoscopy methods rely upon the contrast created by fluorescent stains attached to the object or molecule of interest. This causes limitations due to the impact of the label on the object and its environment, as well as its applicability in vivo, particularly in humans. In this paper, a new label-free approach to visualize small structure with nano-sensitivity to structural alterations is introduced. Numerically synthesized profiles of the axial spatial frequencies are used to probe the structure within areas whose size can be beyond the diffraction resolution limit. Thereafter, nanoscale structural alterations within such areas can be visualized and objects, including biological ones, can be investigated with sub-wavelength resolution, in vivo, in their natural environment. Some preliminary results, including numerical simulations and experiments, which demonstrate the nano-sensitivity and super-resolution ability of our approach, are presented.