High-Sensitivity, High-Throughput Double Sagnac Lateral Shearing Quantitative Phase Microscopy and Tomography with Pseudo-Thermal Illumination

Abstract: Quantitative phase microscopy (QPM) enables label-free measurement of local optical path length variations, providing critical insight into the structure and dynamics of transparent biological specimens. Here, a highly sensitive lateral shearing QPM (LS-QPM) system is presented, based on a novel double Sagnac common-path interferometric configuration combined with pseudo-thermal illumination. The pseudo-thermal light source plays a central role in enhancing spatial phase sensitivity by suppressing coherent noise and speckle artifacts, while maintaining sufficient temporal coherence to generate high-density interference fringes, thereby enabling robust single-shot phase retrieval. In addition, the double Sagnac architecture introduces an inherently stable common-path geometry, significantly enhancing temporal phase stability. Unlike conventional quadriwave lateral shearing interferometry (QWLSI)-based QPM systems, which typically suffer from a trade-off between spatial resolution and field of view (FOV), the proposed approach enables simultaneous achievement of diffraction-limited resolution and a large FOV. Experimental validation using calibrated polystyrene beads demonstrates accurate and spatially uniform phase reconstruction across the entire imaging area. Further, the system's capability for biological imaging is demonstrated through experiments on fixed and live HeLa cells, where subcellular features and dynamic processes are captured in a label-free manner. Furthermore, volumetric imaging of embedded bead samples highlights the potential of the approach for three-dimensional phase tomography. The lateral shearing mechanism, analogous to differential interference contrast (DIC), improves robustness to multiple scattering, indicating strong potential for future applications in imaging thick and heterogeneous samples.