We present a new label-free three-dimensional(3D)microscopy technique,termed transport of intensity diffraction tomography with non-interferometric synthetic aperture(TIDT-NSA).Without resorting to interferometric detection,TIDT-NSA retrieves the 3D refractive index(RI)distribution of biological specimens from 3D intensity-only measurements at various illumination angles,allowing incoherent-diffraction-limited quantitative 3D phase-contrast imaging.The unique combination of z-scanning the sample with illumination angle diversity in TIDT-NSA provides strong defocus phase contrast and better optical sectioning capabilities suitable for high-resolution tomography of thick biological samples.Based on an off-the-shelf bright-field microscope with a programmable light-emitting-diode(LED)illumination source,TIDT-NSA achieves an imaging resolution of 206 nm laterally and 520 nm axially with a high-NA oil immersion objective.We validate the 3D RI tomographic imaging performance on various unlabeled fixed and live samples,including human breast cancer cell lines MCF-7,human hepatocyte carcinoma cell lines HepG2,mouse macrophage cell lines RAW 264.7,Caenorhabditis elegans(C.elegans),and live Henrietta Lacks(HeLa)cells.These results establish TIDT-NSA as a new non-interferometric approach to optical diffraction tomography and 3D label-free microscopy,permitting quantitative characterization of cell morphology and time-dependent subcellular changes for widespread biological and medical applications.

Jiaji Li;Ning Zhou;Jiasong Sun;Shun Zhou;Zhidong Bai;Linpeng Lu;Qian Chen;Chao Zuo

School of Electronic and Optical Engineering,Nanjing University of Science and Technology,No.200 Xiaolingwei Street,Nanjing,Jiangsu Province 210094,China;Jiangsu Key Laboratory of Spectral Imaging&Intelligent Sense,Nanjing University of Science and Technology,Nanjing,Jiangsu Province 210094,China;Smart Computational Imaging Laboratory(SCILab),Nanjing University of Science and Technology,Nanjing,Jiangsu Province 210094,China

光：科学与应用（英文版）

[1]Jiaji Li;Ning Zhou;Jiasong Sun;Shun Zhou;Zhidong Bai;Linpeng Lu;Qian Chen;Chao Zuo-.Transport of intensity diffraction tomography with non-interferometric synthetic aperture for three-dimensional label-free microscopy)[J].光：科学与应用（英文版）,2022(10):2294-2307

TIDT,Henrietta,Lacks

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