Single-image phase retrieval for off-the-shelf Zernike phase-contrast microscopes

Quantitative phase imaging (QPI), such as digital holography, is considered a promising tool in the field of life science due to its noninvasive and quantitative visualization capabilities without the need for fluorescence labeling. However, the popularity of QPI systems is limited due to the cost and complexity of their hardware. In contrast, Zernike phase-contrast microscopy (ZPM) has been widely used in practical scenarios but has not been categorized as QPI, owing to halo and shade-off artifacts and the weak phase condition. Here, we present a single-image phase retrieval method for ZPM that addresses these issues without requiring hardware modifications. By employing a rigorous physical model of ZPM and a gradient descent algorithm for its inversion, we achieve single-shot QPI with an off-the-shelf ZPM system. Our approach is validated in simulations and experiments, demonstrating QPI of a polymer microbead and biological cells. The quantitative nature of our method for single-cell imaging is confirmed through comparisons with observations from an established QPI technique conducted through digital holography. This study paves the way for transforming non-QPI ZPM systems into QPI systems.