Optical diffraction tomography for high resolution live cell imaging.

We report the experimental implementation of optical diffraction tomography for quantitative 3D mapping of refractive index in live biological cells. Using a heterodyne Mach-Zehnder interferometer, we record complex field images of light transmitted through a sample with varying directions of illumination. To quantitatively reconstruct the 3D map of complex refractive index in live cells, we apply optical diffraction tomography based on the Rytov approximation. In this way, the effect of diffraction is taken into account in the reconstruction process and diffraction-free high resolution 3D images are obtained throughout the entire sample volume. The quantitative refractive index map can potentially serve as an intrinsic assay to provide the molecular concentrations without the addition of exogenous agents and also to provide a method for studying the light scattering properties of single cells.

[1]  F. Zernike Phase contrast, a new method for the microscopic observation of transparent objects , 1942 .

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

[3]  A. Devaney Inverse-scattering theory within the Rytov approximation. , 1981, Optics letters.

[4]  K. Tam,et al.  Tomographical imaging with limited-angle input , 1981 .

[5]  V. Perez-Mendez,et al.  TOMOGRAPHICAL IMAGING WITH LIMITED‐ANGLE INPUT , 1982 .

[6]  William R. Brody,et al.  Iterative convolution backprojection algorithms for image reconstruction from limited data , 1983 .

[7]  K. Nugent,et al.  Quantitative optical phase microscopy. , 1998, Optics letters.

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

[9]  K. Nugent,et al.  Quantitative phase tomography , 2000 .

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

[11]  E. Cuche,et al.  Measurement of the integral refractive index and dynamic cell morphometry of living cells with digital holographic microscopy. , 2005, Optics express.

[12]  E. Cuche,et al.  Digital holographic microscopy: a noninvasive contrast imaging technique allowing quantitative visualization of living cells with subwavelength axial accuracy. , 2005, Optics letters.

[13]  R. Dasari,et al.  Diffraction phase microscopy for quantifying cell structure and dynamics. , 2006, Optics letters.

[14]  Suliana Manley,et al.  Optical measurement of cell membrane tension. , 2006, Physical review letters.

[15]  P. Marquet,et al.  Living specimen tomography by digital holographic microscopy: morphometry of testate amoeba. , 2006, Optics express.

[16]  Gabriel Popescu,et al.  Diffraction phase and fluorescence microscopy. , 2006, Optics express.

[17]  K. Badizadegan,et al.  Live cell refractometry using microfluidic devices. , 2006, Optics letters.

[18]  W. Górski,et al.  Tomographic imaging of photonic crystal fibers. , 2007, Optics letters.

[19]  Michael S Feld,et al.  Imaging voltage-dependent cell motions with heterodyne Mach-Zehnder phase microscopy. , 2007, Optics letters.

[20]  Kamran Badizadegan,et al.  Extended depth of focus in tomographic phase microscopy using a propagation algorithm. , 2008, Optics letters.

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

[22]  Yongkeun Park,et al.  Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum , 2008, Proceedings of the National Academy of Sciences.

[23]  Christian Depeursinge,et al.  Simultaneous cell morphometry and refractive index measurement with dual-wavelength Digital Holographic Microscopy , 2008 .

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

[25]  Kamran Badizadegan,et al.  Field-based angle-resolved light-scattering study of single live cells. , 2008, Optics letters.