Generalized reciprocal diffractive imaging for reference-free, single-shot quantitative phase microscopy

Abstract Quantitative phase imaging (QPI) enables label-free measurement of intrinsic optical properties such as the refractive index, offering valuable insights into biological and medical samples. While reciprocal diffractive imaging (RDI) has demonstrated single-shot, reference-free reconstruction of complex optical fields from diffusive samples, its applicability to biological specimens has been limited due to dominant low-frequency components that hinder algorithmic convergence. Here, we present a generalized RDI method that overcomes this limitation by modulating the Fourier spectrum in the pupil plane using a custom-designed Fourier mask and a neutral density (ND) filter. This modification attenuates the DC term and enhances support boundary definition, enabling robust phase retrieval for non-diffusive samples. We validate the proposed method through both simulation and experiments, reconstructing known amplitude and phase objects as well as a range of biological samples including live cells and stained tissue sections. The approach is implemented in a conventional microscope without a reference arm, requiring only a simple pupil-plane modification. Our method provides a compact, non-interferometric solution for high-fidelity QPI and holds significant potential for broad applications in biomedical imaging and real-time dynamic studies.