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

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

doi:10.1038/s41377-022-00815-7

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

Light Sci Appl. 2022 Jun 2;11(1):154. doi: 10.1038/s41377-022-00815-7.

Authors

Jiaji Li^{1

2

3}, Ning Zhou^{1

2

3}, Jiasong Sun^{1

2

3}, Shun Zhou^{1

2

3}, Zhidong Bai^{1

2

3}, Linpeng Lu^{1

2

3}, Qian Chen^{4

5}, Chao Zuo^{6

7

8}

Affiliations

¹ School of Electronic and Optical Engineering, Nanjing University of Science and Technology, No. 200 Xiaolingwei Street, Nanjing, Jiangsu Province, 210094, China.
² Jiangsu Key Laboratory of Spectral Imaging & Intelligent Sense, Nanjing University of Science and Technology, Nanjing, Jiangsu Province, 210094, China.
³ Smart Computational Imaging Laboratory (SCILab), Nanjing University of Science and Technology, Nanjing, Jiangsu Province, 210094, China.
⁴ School of Electronic and Optical Engineering, Nanjing University of Science and Technology, No. 200 Xiaolingwei Street, Nanjing, Jiangsu Province, 210094, China. chenqian@njust.edu.cn.
⁵ Jiangsu Key Laboratory of Spectral Imaging & Intelligent Sense, Nanjing University of Science and Technology, Nanjing, Jiangsu Province, 210094, China. chenqian@njust.edu.cn.
⁶ School of Electronic and Optical Engineering, Nanjing University of Science and Technology, No. 200 Xiaolingwei Street, Nanjing, Jiangsu Province, 210094, China. zuochao@njust.edu.cn.
⁷ Jiangsu Key Laboratory of Spectral Imaging & Intelligent Sense, Nanjing University of Science and Technology, Nanjing, Jiangsu Province, 210094, China. zuochao@njust.edu.cn.
⁸ Smart Computational Imaging Laboratory (SCILab), Nanjing University of Science and Technology, Nanjing, Jiangsu Province, 210094, China. zuochao@njust.edu.cn.

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.

Abstract

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