High-throughput intensity diffraction tomography with a computational microscope.

We demonstrate a motion-free intensity diffraction tomography technique that enables the direct inversion of 3D phase and absorption from intensity-only measurements for weakly scattering samples. We derive a novel linear forward model featuring slice-wise phase and absorption transfer functions using angled illumination. This new framework facilitates flexible and efficient data acquisition, enabling arbitrary sampling of the illumination angles. The reconstruction algorithm performs 3D synthetic aperture using a robust computation and memory efficient slice-wise deconvolution to achieve resolution up to the incoherent limit. We demonstrate our technique with thick biological samples having both sparse 3D structures and dense cell clusters. We further investigate the limitation of our technique when imaging strongly scattering samples. Imaging performance and the influence of multiple scattering is evaluated using a 3D sample consisting of stacked phase and absorption resolution targets. This computational microscopy system is directly built on a standard commercial microscope with a simple LED array source add-on, and promises broad applications by leveraging the ubiquitous microscopy platforms with minimal hardware modifications.

[1]  L. Tian,et al.  3D intensity and phase imaging from light field measurements in an LED array microscope , 2015 .

[2]  A. Kak,et al.  Distortion in Diffraction Tomography Caused by Multiple Scattering , 1983, IEEE Transactions on Medical Imaging.

[3]  Changhuei Yang,et al.  Microscopy refocusing and dark-field imaging by using a simple LED array. , 2011, Optics letters.

[4]  YongKeun Park,et al.  Active illumination using a digital micromirror device for quantitative phase imaging. , 2015, Optics letters.

[5]  Gabriel Popescu,et al.  Synthetic aperture tomographic phase microscopy for 3D imaging of live cells in translational motion. , 2008, Optics express.

[6]  Shalin B. Mehta,et al.  Quantitative phase-gradient imaging at high resolution with asymmetric illumination-based differential phase contrast. , 2009, Optics letters.

[7]  C. Sheppard,et al.  Three-dimensional transfer functions for high-aperture systems , 1994 .

[8]  Ose,et al.  Optical diffraction tomography with fully and partially coherent illumination in high numerical aperture label-free microscopy , 2018 .

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

[10]  Demetri Psaltis,et al.  Optical Tomographic Image Reconstruction Based on Beam Propagation and Sparse Regularization , 2016, IEEE Transactions on Computational Imaging.

[11]  Mario Bertero,et al.  Introduction to Inverse Problems in Imaging , 1998 .

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

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

[14]  Marc Levoy,et al.  Light field microscopy , 2006, ACM Trans. Graph..

[15]  C. Fang-Yen,et al.  Optical diffraction tomography for high resolution live cell imaging. , 2009, Optics express.

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

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

[18]  B. Wattellier,et al.  Enhanced 3D spatial resolution in quantitative phase microscopy using spatially incoherent illumination. , 2014, Optics express.

[19]  M. Schmid Principles Of Optics Electromagnetic Theory Of Propagation Interference And Diffraction Of Light , 2016 .

[20]  E. Cuche,et al.  Cell refractive index tomography by digital holographic microscopy. , 2006, Optics letters.

[21]  L. Tian,et al.  3D differential phase-contrast microscopy with computational illumination using an LED array. , 2014, Optics letters.

[22]  J. Rodrigo,et al.  Optical diffraction tomography with fully and partially coherent illumination in high numerical aperture label-free microscopy [Invited]. , 2018, Applied optics.

[23]  Greg Gbur,et al.  Image reconstruction in spherical-wave intensity diffraction tomography. , 2005, Journal of the Optical Society of America. A, Optics, image science, and vision.

[24]  J. Rodrigo,et al.  Fast label-free microscopy technique for 3D dynamic quantitative imaging of living cells. , 2017, Biomedical optics express.

[25]  YongKeun Park,et al.  Simultaneous 3D visualization and position tracking of optically trapped particles using optical diffraction tomography , 2015 .

[26]  N. Streibl Three-dimensional imaging by a microscope , 1985 .

[27]  Greg Gbur,et al.  Spherical-wave intensity diffraction tomography. , 2005, Journal of the Optical Society of America. A, Optics, image science, and vision.

[28]  Greg Gbur,et al.  Hybrid diffraction tomography without phase information. , 2002, Journal of the Optical Society of America. A, Optics, image science, and vision.

[29]  Jonathan Bailleul,et al.  Tomographic diffractive microscopy with isotropic resolution , 2017 .

[30]  Kyoohyun Kim,et al.  Synthetic Fourier transform light scattering. , 2013, Optics express.

[31]  Hugues Giovannini,et al.  Far-field diffraction microscopy at λ/10 resolution , 2016 .

[32]  E. Manders,et al.  Controlled light-exposure microscopy reduces photobleaching and phototoxicity in fluorescence live-cell imaging , 2007, Nature Biotechnology.

[33]  E. Wolf Three-dimensional structure determination of semi-transparent objects from holographic data , 1969 .

[34]  Greg Gbur,et al.  Diffraction tomography without phase information. , 2002, Optics letters.

[35]  Mor Habaza,et al.  Tomographic phase microscopy with 180° rotation of live cells in suspension by holographic optical tweezers. , 2015, Optics letters.

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

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

[38]  N. Streibl Phase imaging by the transport equation of intensity , 1984 .

[39]  S. D. Babacan,et al.  White-light diffraction tomography of unlabelled live cells , 2014, Nature Photonics.

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

[41]  Victoria J Allan,et al.  Light Microscopy Techniques for Live Cell Imaging , 2003, Science.

[42]  YongKeun Park,et al.  Tomographic active optical trapping of arbitrarily shaped objects by exploiting 3D refractive index maps , 2017, Nature communications.

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

[44]  B. Chen,et al.  Validity of diffraction tomography based on the first born and the first rytov approximations. , 1998, Applied optics.

[45]  T. Gaylord,et al.  Three-dimensional quantitative phase imaging via tomographic deconvolution phase microscopy. , 2015, Applied optics.

[46]  Youngchan Kim,et al.  Common-path diffraction optical tomography for investigation of three-dimensional structures and dynamics of biological cells. , 2014, Optics express.

[47]  Anthony J. Devaney,et al.  Phase-retrieval and intensity-only reconstruction algorithms for optical diffraction tomography , 1993 .

[48]  S. van de Linde,et al.  Light-induced cell damage in live-cell super-resolution microscopy , 2015, Scientific Reports.

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

[50]  Laura Waller,et al.  3D differential phase contrast microscopy , 2016, SPIE BiOS.

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