he refractive index (RI) of cells and tissues is emerging as a promising non-invasive biomarker for diagnosing and treating diseases in pathophysiology. However, conventional RI measurement methods using laser interferometry have limitations, such as the need for multiple image acquisitions or bulky interferometers, which compromise imaging speed and stability. Non-interferometric approaches have been explored but often require multiple intensity measurements for RI reconstruction.

To address these challenges, we present a single-shot non-interferometric imaging method for directly obtaining the RI image of the in-focus slice. By utilizing spectral multiplexing and optical transfer function engineering, we simultaneously measure three optimized intensity images with different illuminations. The RI distribution of the sample is obtained through deconvolution of the captured intensity images. Our optical setup, using cost-effective Fresnel lenses and an LCD, is compact and efficient. We successfully measured various biological cells with subcellular resolution and high spatiotemporal stability.

This proposed approach has broad applications in biological studies of pathophysiology, immunology, and developmental biology, where visualization of living systems or high-throughput RI imaging of dynamic biospecimens is crucial. It offers a valuable tool for non-invasive disease assessment and monitoring, potentially advancing diagnosis and treatment methodologies.