Wide-field high-resolution 3D microscopy with Fourier ptychographic diffraction tomography

We report a computational 3D microscopy technique, termed Fourier ptychographic diffraction tomography (FPDT), that iteratively stitches together numerous variably illuminated, low-resolution images acquired with a low-numerical aperture (NA) objective in 3D Fourier space to create a wide field-of-view (FOV), high-resolution, depth-resolved complex refractive index (RI) image across large volumes. Unlike conventional optical diffraction tomography (ODT) approaches that rely on controlled bright-field illumination, holographic phase measurement, and high-NA objective detection, FPDT employs tomographic RI reconstruction from low-NA intensity-only measurements. In addition, FPDT incorporates high-angle dark-field illuminations beyond the NA of the objective, significantly expanding the accessible object frequency. With FPDT, we present the highest-throughput ODT results with 390 nm lateral resolution and 899 nm axial resolution across a 10 × FOV of 1.77 mm2 and a depth of focus of ~ 20 µm. Billion-voxel 3D tomographic imaging results of biological samples establish FPDT as a powerful non-invasive and label-free tool for high-throughput 3D microscopy applications.