Quantitative phase imaging (QPI) with its high-contrast images of optical phase delay (OPD) maps is often used for label-free single-cell analysis. Contrary to other imaging methods, sensitivity improvement has not been intensively explored because conventional QPI is sensitive enough to observe the surface roughness of a substrate that restricts the minimum measurable OPD. However, emerging QPI techniques that utilize, for example, differential image analysis of consecutive temporal frames, such as mid-infrared photothermal QPI, mitigate the minimum OPD limit by decoupling the static OPD contribution and allow measurement of much smaller OPDs. Here, we propose and demonstrate supersensitive QPI with an expanded dynamic range. It is enabled by adaptive dynamic range shift through a combination of wavefront shaping and dark-field QPI techniques. As a proof-of-concept demonstration, we show dynamic range expansion (sensitivity improvement) of QPI by a factor of 6.6 and its utility in improving the sensitivity of mid-infrared photothermal QPI. This technique can also be applied for wide-field scattering imaging of dynamically changing nanoscale objects inside and outside a biological cell without losing global cellular morphological image information.

Light: Science & Applications 10, 1 (2021), UTokyoFOCUS

We present a single-image numerical phase retrieval method for Zernike phase-contrast microscopy (ZPM) that addresses halo and shade-off artifacts, as well as the weak phase condition, without requiring hardware modifications. By employing a rigorous physical model of ZPM and a gradient descent algorithm for its inversion, we achieve quantitative ZPM imaging. Our approach is experimentally validated using biological cells and its quantitative nature is confirmed through comparisons with digital holography observations.

arXiv:2305.05156