Correlative three-dimensional fluorescence and refractive index tomography: bridging the gap between molecular specificity and quantitative bioimaging.

Optical diffraction tomography (ODT) provides label-free three-dimensional (3D) refractive index (RI) measurement of biological samples. However, due to the nature of the RI values of biological specimens, ODT has limited access to molecular specific information. Here, we present an optical setup combining ODT with three-channel 3D fluorescence microscopy, to enhance the molecular specificity of the 3D RI measurement. The 3D RI distribution and 3D deconvoluted fluorescence images of HeLa cells and NIH-3T3 cells are measured, and the cross-correlative analysis between RI and fluorescence of live cells are presented.

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

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

[3]  YongKeun Park,et al.  Measurements of morphological and biophysical alterations in individual neuron cells associated with early neurotoxic effects in Parkinson's disease , 2017, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[4]  Kyoohyun Kim,et al.  Three-dimensional label-free imaging and quantification of lipid droplets in live hepatocytes , 2016, Scientific Reports.

[5]  YongKeun Park,et al.  High-resolution three-dimensional imaging of red blood cells parasitized by Plasmodium falciparum and in situ hemozoin crystals using optical diffraction tomography , 2013, Journal of biomedical optics.

[6]  SangYun Lee,et al.  Refractive index tomograms and dynamic membrane fluctuations of red blood cells from patients with diabetes mellitus , 2017 .

[7]  YongKeun Park,et al.  Time-multiplexed structured illumination using a DMD for optical diffraction tomography. , 2017, Optics letters.

[8]  YoungJu Jo,et al.  Quantitative Phase Imaging Techniques for the Study of Cell Pathophysiology: From Principles to Applications , 2013, Sensors.

[9]  Jonghee Yoon,et al.  Optical diffraction tomography using a digital micromirror device for stable measurements of 4D refractive index tomography of cells , 2016, SPIE BiOS.

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

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

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

[13]  J. Guck,et al.  Cell nuclei have lower refractive index and mass density than cytoplasm , 2016, Journal of biophotonics.

[14]  E. Cuche,et al.  Spatial filtering for zero-order and twin-image elimination in digital off-axis holography. , 2000, Applied optics.

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

[16]  Joseph A Izatt,et al.  Structured illumination multimodal 3D-resolved quantitative phase and fluorescence sub-diffraction microscopy. , 2017, Biomedical optics express.

[17]  Jong Chul Ye,et al.  Real-time Visualization of 3-d Dynamic Microscopic Objects Using Optical Diffraction Tomography References and Links , 2022 .

[18]  YongKeun Park,et al.  Holotomography: refractive index as an intrinsic imaging contrast for 3-D label-free live cell imaging , 2017, bioRxiv.

[19]  Subra Suresh,et al.  Biophysics of Malarial Parasite Exit from Infected Erythrocytes , 2011, PloS one.

[20]  Im,et al.  Correlative three-dimensional fluorescence and refractive index tomography : bridging the gap between molecular specificity and quantitative bioimaging , 2017 .

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

[22]  Kyoohyun Kim,et al.  Melittin-induced alterations in morphology and deformability of human red blood cells using quantitative phase imaging techniques , 2016, bioRxiv.

[23]  Joseph M. Martel,et al.  Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel. , 2014, Physical review applied.

[24]  Pilhan Kim,et al.  Holographic intravital microscopy for 2-D and 3-D imaging intact circulating blood cells in microcapillaries of live mice , 2016, Scientific Reports.

[25]  Gabriel Popescu,et al.  Optical imaging of cell mass and growth dynamics. , 2008, American journal of physiology. Cell physiology.

[26]  Ang,et al.  Diffraction tomography with Fourier ptychography : supplementary material , 2016 .

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

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

[29]  YongKeun Park,et al.  Measuring cell surface area and deformability of individual human red blood cells over blood storage using quantitative phase imaging , 2016, Scientific Reports.

[30]  A G Hoekstra,et al.  Osmotic response of lymphocytes measured by means of forward light scattering: theoretical considerations. , 1988, Cytometry.

[31]  Michael B. Wallace,et al.  Observation of periodic fine structure in reflectance from biological tissue: A new technique for measuring nuclear size distribution , 1998 .

[32]  P. Brown,et al.  On the distribution of protein refractive index increments. , 2011, Biophysical journal.

[33]  Hongying Zhu,et al.  Optofluidic Tomography on a Chip. , 2011, Applied physics letters.

[34]  Jong Chul Ye,et al.  Comparative study of iterative reconstruction algorithms for missing cone problems in optical diffraction tomography. , 2015, Optics express.

[35]  Sung-Hee Hong,et al.  Characterizations of individual mouse red blood cells parasitized by Babesia microti using 3-D holographic microscopy , 2015, Scientific Reports.

[36]  M. Takeda,et al.  Fourier-transform method of fringe-pattern analysis for computer-based topography and interferometry , 1982 .

[37]  YongKeun Park,et al.  Hyperspectral optical diffraction tomography. , 2016, Optics express.

[38]  Bryant B. Chhun,et al.  Super-Resolution Video Microscopy of Live Cells by Structured Illumination , 2009, Nature Methods.

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

[40]  V. Lauer.  New approach to optical diffraction tomography yielding a vector equation of diffraction tomography and a novel tomographic microscope , 2002, Journal of microscopy.

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

[42]  Pasquale Memmolo,et al.  Tomographic flow cytometry by digital holography , 2016, Light: Science & Applications.

[43]  J Beuthan,et al.  The spatial variation of the refractive index in biological cells. , 1996, Physics in medicine and biology.

[44]  R. Barer.  Determination of Dry Mass, Thickness, Solid and Water Concentration in Living Cells , 1953, Nature.

[45]  Kyoohyun Kim,et al.  Optical diffraction tomography techniques for the study of cell pathophysiology , 2016, 1603.00592.

[46]  M. Gustafsson.  Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy , 2000, Journal of microscopy.