Transport-of-intensity Fourier ptychographic diffraction tomography: defying the matched illumination condition

Abstract

Optical diffraction tomography (ODT) is a promising label-free three-dimensional (3D) microscopic method capable of measuring the 3D refractive index (RI) distribution of optically transparent samples (e.g., unlabeled biological cells). In recent years, non-interferometric ODT techniques have received increasing attention for their system simplicity, speckle-free imaging quality, and compatibility with existing microscopes. However, ODT methods for implementing non-interferometric measurements in high numerical aperture (NA) microscopy systems are often plagued by low-frequency missing problems—a consequence of violating the matched illumination condition. Here, we present transport-of-intensity Fourier ptychographic diffraction tomography (TI-FPDT) to address this challenging issue by combining ptychographic angular diversity with additional “transport of intensity” measurements. TI-FPDT exploits the defocused phase contrast to circumvent the stringent requirement on the illumination NA imposed by the matched illumination condition. It effectively overcomes the reconstruction quality deterioration and RI underestimation problems in conventional FPDT, as demonstrated by high-resolution tomographic imaging of various unlabeled transparent samples (including microspheres, USAF targets, HeLa cells, and C2C12 cells). Due to its simplicity and effectiveness, TI-FPDT is anticipated to open new possibilities for label-free 3D microscopy in various biomedical applications.