Three‐dimensional correlative single‐cell imaging utilizing fluorescence and refractive index tomography

Cells alter the path of light, a fact that leads to well-known aberrations in single cell or tissue imaging. Optical diffraction tomography (ODT) measures the biophysical property that causes these aberrations, the refractive index (RI). ODT is complementary to fluorescence imaging and does not require any markers. The present study introduces RI and fluorescence tomography with optofluidic rotation (RAFTOR) of suspended cells, facilitating the segmentation of the 3D-correlated RI and fluorescence data for a quantitative interpretation of the nuclear RI. The technique is validated with cell phantoms and used to confirm a lower nuclear RI for HL60 cells. Furthermore, the nuclear inversion of adult mouse photoreceptor cells is observed in the RI distribution. The applications shown confirm predictions of previous studies and illustrate the potential of RAFTOR to improve our understanding of cells and tissues.

[1]  Jochen Guck,et al.  Quantifying cellular differentiation by physical phenotype using digital holographic microscopy. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[2]  Anna V. Taubenberger,et al.  A pH-driven transition of the cytoplasm from a fluid- to a solid-like state promotes entry into dormancy , 2016, eLife.

[3]  Elias Kristensson,et al.  FRAME: femtosecond videography for atomic and molecular dynamics , 2017, Light: Science & Applications.

[4]  Chau-Jern Cheng,et al.  Sectional imaging of spatially refractive index distribution using coaxial rotation digital holographic microtomography , 2014 .

[5]  Aaas News,et al.  Book Reviews , 1893, Buffalo Medical and Surgical Journal.

[6]  W. Marsden I and J , 2012 .

[7]  William J. Polacheck,et al.  Noncontact three-dimensional mapping of intracellular hydro-mechanical properties by Brillouin microscopy , 2015, Nature Methods.

[8]  Jing-Wei Su,et al.  Digital holographic microtomography for high‐resolution refractive index mapping of live cells , 2013, Journal of biophotonics.

[9]  L. E. Larsen,et al.  Limitations of Imaging with First-Order Diffraction Tomography , 1984 .

[10]  R. Barer Interference Microscopy and Mass Determination , 1952, Nature.

[11]  S. Anna,et al.  Microfluidic methods for generating continuous droplet streams , 2007 .

[12]  A. Devaney A filtered backpropagation algorithm for diffraction tomography. , 1982, Ultrasonic imaging.

[13]  Jochen Guck,et al.  Refractive index measurements of single, spherical cells using digital holographic microscopy. , 2018, Methods in cell biology.

[14]  Marta Ibisate,et al.  Refractive Index Properties of Calcined Silica Submicrometer Spheres , 2002 .

[15]  Joseph A. Izatt,et al.  Refractive index tomography with structured illumination , 2017, 1702.03595.

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

[17]  Vladislav V. Yakovlev,et al.  Seeing cells in a new light: a renaissance of Brillouin spectroscopy , 2016 .

[18]  O. Haeberlé,et al.  Holographic microscopy and diffractive microtomography of transparent samples , 2008 .

[19]  B. Kemper,et al.  Digital holographic microscopy for live cell applications and technical inspection. , 2008, Applied optics.

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

[21]  Annie Chateau,et al.  Exact approaches for scaffolding , 2015, BMC Bioinformatics.

[22]  J. Guck,et al.  Direct observation of light focusing by single photoreceptor cell nuclei. , 2014, Optics express.

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

[24]  Yongjin Sung,et al.  Stain-Free Quantification of Chromosomes in Live Cells Using Regularized Tomographic Phase Microscopy , 2012, PloS one.

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

[26]  Jochen Guck,et al.  Viscoelastic properties of individual glial cells and neurons in the CNS , 2006, Proceedings of the National Academy of Sciences.

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

[28]  Changhuei Yang,et al.  Cellular organization and substructure measured using angle-resolved low-coherence interferometry. , 2002, Biophysical journal.

[29]  Adam Wax,et al.  Is the nuclear refractive index lower than cytoplasm? Validation of phase measurements and implications for light scattering technologies , 2017, Journal of biophotonics.

[30]  Christian Dietrich,et al.  The optical cell rotator. , 2008, Optics express.

[31]  R. Stephenson A and V , 1962, The British journal of ophthalmology.

[32]  Dean C Ripple,et al.  The Use of Index-Matched Beads in Optical Particle Counters , 2014, Journal of research of the National Institute of Standards and Technology.

[33]  S. Lung,et al.  Effects of Extreme Precipitation to the Distribution of Infectious Diseases in Taiwan, 1994–2008 , 2012, PloS one.

[34]  Stefan Schinkinger,et al.  Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. , 2005, Biophysical journal.

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

[36]  Serge Monneret,et al.  Optical detection and measurement of living cell morphometric features with single-shot quantitative phase microscopy. , 2012, Journal of biomedical optics.

[37]  J. Käs,et al.  Reactive glial cells: increased stiffness correlates with increased intermediate filament expression , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

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

[39]  Graeme Whyte,et al.  Optofluidic rotation of living cells for single‐cell tomography , 2015, Journal of biophotonics.

[40]  Stefan Schinkinger,et al.  High-throughput rheological measurements with an optical stretcher. , 2007, Methods in cell biology.

[41]  Maria Carmo-Fonseca,et al.  To be or not to be in the nucleolus , 2000, Nature Cell Biology.

[42]  Christian Depeursinge,et al.  Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy , 2010, Journal of biophotonics.

[43]  H. G. Davies,et al.  Interference Microscopy and Mass Determination , 1952, Nature.

[44]  J. Käs,et al.  The optical stretcher: a novel laser tool to micromanipulate cells. , 2001, Biophysical journal.

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

[46]  Jochen Guck,et al.  Single-cell diffraction tomography with optofluidic rotation about a tilted axis , 2015, SPIE NanoScience + Engineering.

[47]  A. Hyman,et al.  Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation , 2009, Science.

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

[49]  J. Guck,et al.  Physical insight into light scattering by photoreceptor cell nuclei. , 2010, Optics letters.

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

[51]  Thomas Cremer,et al.  Nuclear Architecture of Rod Photoreceptor Cells Adapts to Vision in Mammalian Evolution , 2009, Cell.

[52]  M. Glas,et al.  Principles of Computerized Tomographic Imaging , 2000 .

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

[54]  Ichiro Yamada,et al.  Diffraction microtomography with sample rotation: influence of a missing apple core in the recorded frequency space , 2008 .

[55]  P. F. Mullaney,et al.  Differential light scattering from spherical mammalian cells. , 1974, Biophysical journal.

[56]  Stefan Schinkinger,et al.  Reconfigurable microfluidic integration of a dual-beam laser trap with biomedical applications , 2007, Biomedical microdevices.

[57]  J. Kostencka,et al.  Accurate approach to capillary-supported optical diffraction tomography. , 2015, Optics express.

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

[59]  Kevin Barraclough,et al.  I and i , 2001, BMJ : British Medical Journal.

[60]  B. Wattellier,et al.  Quadriwave lateral shearing interferometry for quantitative phase microscopy of living cells. , 2009, Optics express.

[61]  Bertrand Simon,et al.  High‐resolution tomographic diffractive microscopy of biological samples , 2010, Journal of biophotonics.

[62]  D. Agard,et al.  Computational adaptive optics for live three-dimensional biological imaging , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[63]  Natan T. Shaked,et al.  Rapid 3D Refractive‐Index Imaging of Live Cells in Suspension without Labeling Using Dielectrophoretic Cell Rotation , 2016, Advanced science.

[64]  Paul Müller,et al.  ODTbrain: a Python library for full-view, dense diffraction tomography , 2015, BMC Bioinformatics.

[65]  Robin Diekmann,et al.  Nanoscopy of bacterial cells immobilized by holographic optical tweezers , 2016, Nature Communications.

[66]  Marco Y. Hein,et al.  A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation , 2015, Cell.

[67]  J. Guck,et al.  The Theory of Diffraction Tomography , 2015, 1507.00466.