Nano-sensitive optical coherence tomography.

Depth resolved label-free detection of structural changes with nanoscale sensitivity is an outstanding problem in the biological and physical sciences and has significant applications in both the fundamental research and healthcare diagnostics arenas. Here we experimentally demonstrate a novel label-free depth resolved sensing technique based on optical coherence tomography (OCT) to detect structural changes at the nanoscale. Structural components of the 3D object, spectrally encoded in the remitted light, are transformed from the Fourier domain into each voxel of the 3D OCT image without compromising sensitivity. Spatial distribution of the nanoscale structural changes in the depth direction is visualized in just a single OCT scan. This label free approach provides new possibilities for depth resolved study of pathogenic and physiologically relevant molecules in the body with high sensitivity and specificity. It offers a powerful opportunity for early diagnosis and treatment of diseases. Experimental results show the ability of the approach to differentiate structural changes of 30 nm in nanosphere aggregates, located at different depths, from a single OCT scan, and structural changes less than 30 nm in time from two OCT scans. Application for visualization of the structure of human skin in vivo is also demonstrated.