Label-free quantitative 3D intensity diffraction tomographic imaging in high numerical aperture microscopy

We propose label-free and motion-free resolution-enhanced intensity diffraction tomography recovering the 3D complex refractive index distribution of an object. By combining an annular illumination strategy with a high numerical aperture (NA) condenser, we achieve near diffraction-limited lateral resolution of 346 nm and axial resolution of 1.2 µm over 130 130 8 µm3 volume. Our annular pattern matches the system’s maximum NA to reduce the data requirement to 48 intensity frames. The small data requirement and high resolution enable fast 3D quantitative refractive index imaging of biological cells across hundreds of nanometers scales. The reIDT system is directly built on a standard commercial microscope with a simple LED array source and condenser lens adds-on, and promises broad applications for natural biological imaging with minimal hardware modifications. To test the capabilities of our technique, we present the 3D complex refractive index reconstructions on the Henrietta Lacks (HeLa) and HT29 human cancer cells. Our work provides an important step in intensity-based diffraction tomography towards high resolution imaging applications.

[1]  D. Louvard,et al.  Absorptive and mucus-secreting subclones isolated from a multipotent intestinal cell line (HT-29) provide new models for cell polarity and terminal differentiation , 1987, The Journal of cell biology.

[2]  Chao Zuo,et al.  Single-shot isotropic quantitative phase microscopy based on color-multiplexed differential phase contrast , 2019, APL Photonics.

[3]  Chao Zuo,et al.  Three-dimensional tomographic microscopy technique with multi-frequency combination with partially coherent illuminations. , 2018, Biomedical optics express.

[4]  Jihong Zhang,et al.  A novel cycloartane triterpenoid from Cimicifuga induces apoptotic and autophagic cell death in human colon cancer HT-29 cells. , 2017, Oncology reports.

[5]  Kyoohyun Kim,et al.  Label-free characterization of white blood cells by measuring 3D refractive index maps. , 2015, Biomedical optics express.

[6]  Michael Unser,et al.  Learning approach to optical tomography , 2015, 1502.01914.

[7]  Tan H. Nguyen,et al.  Gradient light interference microscopy for 3D imaging of unlabeled specimens , 2017, Nature Communications.

[8]  Lei Tian,et al.  High-throughput intensity diffraction tomography with a computational microscope. , 2018, Biomedical optics express.

[9]  Qian Chen,et al.  Efficient positional misalignment correction method for Fourier ptychographic microscopy. , 2016, Biomedical optics express.

[10]  R. Horstmeyer,et al.  Wide-field, high-resolution Fourier ptychographic microscopy , 2013, Nature Photonics.

[11]  Alex Matlock,et al.  High-throughput, volumetric quantitative phase imaging with multiplexed intensity diffraction tomography. , 2019, Biomedical optics express.

[12]  L. Tian,et al.  Optimal illumination scheme for isotropic quantitative differential phase contrast microscopy , 2019, Photonics Research.

[13]  Björn Kemper,et al.  Tomographic phase microscopy of living three-dimensional cell cultures , 2014, Journal of biomedical optics.

[14]  Qian Chen,et al.  Optimal principal component analysis-based numerical phase aberration compensation method for digital holography. , 2016, Optics letters.

[15]  A. Ozcan,et al.  On the use of deep learning for computational imaging , 2019, Optica.

[16]  Guoan Zheng,et al.  Quantitative phase imaging via Fourier ptychographic microscopy. , 2013, Optics letters.

[17]  Chao Zuo,et al.  Highly efficient quantitative phase microscopy using programmable annular LED illumination , 2017, 1707.04003.

[18]  A. Asundi,et al.  High-resolution transport-of-intensity quantitative phase microscopy with annular illumination , 2017, Scientific Reports.

[19]  Lei Tian,et al.  Reliable deep-learning-based phase imaging with uncertainty quantification. , 2019 .

[20]  P. Marquet,et al.  Marker-free phase nanoscopy , 2013, Nature Photonics.

[21]  C. Fang-Yen,et al.  Tomographic phase microscopy , 2008, Nature Methods.

[22]  Qian Chen,et al.  Adaptive step-size strategy for noise-robust Fourier ptychographic microscopy. , 2016, Optics express.

[23]  L. Tian,et al.  Quantitative differential phase contrast imaging in an LED array microscope. , 2015, Optics express.

[24]  Chao Zuo,et al.  Transport of intensity equation: a tutorial , 2020 .

[25]  Yibo Zhang,et al.  Phase recovery and holographic image reconstruction using deep learning in neural networks , 2017, Light: Science & Applications.

[26]  A. Asundi,et al.  Wide-field high-resolution 3D microscopy with Fourier ptychographic diffraction tomography , 2019, Optics and Lasers in Engineering.

[27]  Qian Chen,et al.  Optimal illumination pattern for transport-of-intensity quantitative phase microscopy. , 2018, Optics express.

[28]  L. Tian,et al.  The transport of intensity equation for optical path length recovery using partially coherent illumination. , 2013, Optics express.

[29]  Chao Zuo,et al.  Resolution-enhanced Fourier ptychographic microscopy based on high-numerical-aperture illuminations , 2017, Scientific Reports.

[30]  L. Tian,et al.  Transport of Intensity phase-amplitude imaging with higher order intensity derivatives. , 2010, Optics express.

[31]  Qian Chen,et al.  Transport-of-intensity phase imaging using Savitzky-Golay differentiation filter--theory and applications. , 2013, Optics express.

[32]  Kannan Ramchandran,et al.  Multiplexed coded illumination for Fourier Ptychography with an LED array microscope. , 2014, Biomedical optics express.

[33]  R. Horstmeyer,et al.  Diffraction tomography with Fourier ptychography. , 2015, Optica.

[34]  Lei Tian,et al.  Deep speckle correlation: a deep learning approach toward scalable imaging through scattering media , 2018, Optica.

[35]  J. Rodrigo,et al.  Rapid quantitative phase imaging for partially coherent light microscopy. , 2014, Optics express.

[36]  Yongkeun Park,et al.  Kramers–Kronig holographic imaging for high-space-bandwidth product , 2019, Optica.

[37]  P. Ferraro,et al.  Quantitative phase-contrast microscopy by a lateral shear approach to digital holographic image reconstruction. , 2006, Optics letters.

[38]  Laura Waller,et al.  Computational illumination for high-speed in vitro Fourier ptychographic microscopy , 2015, 1506.04274.

[39]  Chao Zuo,et al.  Optical diffraction tomography microscopy with transport of intensity equation using a light-emitting diode array , 2017 .

[40]  A. Asundi,et al.  High-speed transport-of-intensity phase microscopy with an electrically tunable lens. , 2013, Optics express.

[41]  Liang Zhang,et al.  Fringe pattern analysis using deep learning , 2018, Advanced Photonics.

[42]  J. Rodrigo,et al.  Label-free quantitative 3D tomographic imaging for partially coherent light microscopy. , 2017, Optics express.