My Research

Our recent work published at Light: Science & Applications 12, 200 (2023). Resolving three-dimensional morphological features in thick specimens remains a significant challenge for label-free imaging. We report a new speckle diffraction tomography (SDT) approach that can image thick biological specimens with ~500 nm lateral resolution and ~1 μm axial resolution in a reflection geometry.In SDT, multiple-scattering background is rejected through spatiotemporal gating provided by dynamic speckle-field interferometry, while depth-resolved refractive index maps are reconstructed by developing a comprehensive inverse-scattering model that also considers specimen-induced aberrations. Benefiting from the high-resolution and full-field quantitative imaging capabilities of SDT, we successfully imaged red blood cells and quantified their membrane fluctuations behind a turbid medium with a thickness of 2.8 scattering mean-free paths. Most importantly, we performed volumetric imaging of cornea inside an ex vivo rat eye and quantified its optical properties, including the mapping of nanoscale topographic features of Dua’s and Descemet’s membranes that had not been previously visualized.

Our recent work has been published in Nature Communications 13, 3465 (2022). Quantitative characterisation of micro-scale mechanical properties of the extracellular matrix (ECM) and dynamic cell-ECM interactions can significantly enhance fundamental discoveries and their translational potential in the rapidly growing field of mechanobiology. However, quantitative 3D imaging of ECM mechanics with cellular-scale resolution and dynamic monitoring of cell-mediated changes to pericellular viscoelasticity remain a challenge for existing mechanical characterisation methods. Here, we present light-sheet photonic force optical coherence elastography (LS-pfOCE) to address this need by leveraging a light-sheet for parallelised, non-invasive, and localised mechanical loading. We demonstrate the capabilities of LS-pfOCE by imaging the micromechanical heterogeneity of fibrous collagen matrices and perform live-cell imaging of cell-mediated ECM micromechanical dynamics. By providing access to 4D spatiotemporal variations in the micromechanical properties of 3D biopolymer constructs and engineered cellular systems, LS-pfOCE has the potential to drive new discoveries in mechanobiology and contribute to the development of novel biomechanics-based clinical diagnostics and therapies.