Wavelength-encoded reflection matrix for nano-scale quantitative phase tomography with breaking-through diffraction-limit resolution

Quantitative phase microscopy (QPM) has emerged as a valuable method for cell and tissue research due to its lower phototoxicity and no photobleaching. Interference-based phase microscopy is typically dependent on establishing the relationship between the optical path difference (OPD) and phase to accomplish label-free three-dimensional (3D) imaging. However, the 3D imaging in this case merely depicts the surface morphology of the samples, without providing depth information. The development of a wavelength-encoding reflection matrix Quantitative phase tomography (RM-QPT) with ultra-high axial resolution of 8 nm has enabled the realisation of tomographic imaging. Initially, a standard resolution target testing experiment was employed to demonstrate the lateral resolution of RM-QPT, which has been shown to enhance the diffraction limit value by 22 %. Additionally, the system has been demonstrated to provide an imaging speed of 1 second for a volume of 300 × 300 × 5 μm 3 . Subsequently, the 3D OPD-based phase tomography imaging performance is validated for quantitative analysis of the brain slice of the ventricle and nucleus accumbens in mice. In comparison with conventional commercial phase microscopy, our system is capable of detecting the absence of cerebrospinal fluid. At last, a comparison of the imaging results of ex-vivo pig intestinal tissue demonstrated that OPD-based structural imaging provides greater detail and clarity than fluorescence-based techniques. This work paves the way towards a new computational phase tomography with nano-scale axial resolution, breakthrough diffraction-limit lateral resolution, and high-speed imaging features for label-free biomedical research and endoscopy applications.