Transport of intensity diffraction tomography with non-interferometric synthetic aperture for three-dimensional label-free microscopy

Autor: Jiaji Li, Ning Zhou, Jiasong Sun, Shun Zhou, Zhidong Bai, Linpeng Lu, Qian Chen, Chao Zuo
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Light: Science & Applications, Vol 11, Iss 1, Pp 1-14 (2022)
Druh dokumentu: article
ISSN: 2047-7538
DOI: 10.1038/s41377-022-00815-7
Popis: Abstract 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.
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