Multimode fibre: Light-sheet microscopy at the tip of a needle

Light-sheet fluorescence microscopy has emerged as a powerful platform for 3-D volumetric imaging in the life sciences. Here, we introduce an important step towards its use deep inside biological tissue. Our new technique, based on digital holography, enables delivery of the light-sheet through a multimode optical fibre – an optical element with extremely small footprint, yet permitting complex control of light transport processes within. We show that this approach supports some of the most advanced methods in light-sheet microscopy: by taking advantage of the cylindrical symmetry of the fibre, we facilitate the wavefront engineering methods for generation of both Bessel and structured Bessel beam plane illumination. Finally, we assess the quality of imaging on a sample of fluorescent beads fixed in agarose gel and we conclude with a proof-of-principle imaging of a biological sample, namely the regenerating operculum prongs of Spirobranchus lamarcki.

[1]  Y. Silberberg,et al.  Parallel transmission of images through single optical fibers , 1983, Proceedings of the IEEE.

[2]  F. Del Bene,et al.  Optical Sectioning Deep Inside Live Embryos by Selective Plane Illumination Microscopy , 2004, Science.

[3]  Tomáš Čižmár,et al.  Seeing through chaos in multimode fibres , 2015, Nature Photonics.

[4]  Tomáš Čižmár,et al.  Shaping the light transmission through a multimode optical fibre: complex transformation analysis and applications in biophotonics. , 2011, Optics express.

[5]  Moonseok Kim,et al.  Scanner-free and wide-field endoscopic imaging by using a single multimode optical fiber. , 2012, Physical review letters.

[6]  Fritjof Helmchen,et al.  Miniaturized selective plane illumination microscopy for high-contrast in vivo fluorescence imaging. , 2010, Optics letters.

[7]  Tomáš Čižmár,et al.  Wavefront corrected light sheet microscopy in turbid media , 2012 .

[8]  Tomáš Čižmár,et al.  Compact multimode fiber beam-shaping system based on GPU accelerated digital holography. , 2015, Optics letters.

[9]  A. Rohrbach,et al.  Microscopy with self-reconstructing beams , 2010 .

[10]  M. Davidson,et al.  Rapid three-dimensional isotropic imaging of living cells using Bessel beam plane illumination , 2011, Nature Methods.

[11]  Demetri Psaltis,et al.  Delivery of focused short pulses through a multimode fiber. , 2014, Optics express.

[12]  Philipp J. Keller,et al.  Reconstruction of Zebrafish Early Embryonic Development by Scanned Light Sheet Microscopy , 2008, Science.

[13]  Wesley R. Legant,et al.  Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution , 2014, Science.

[14]  Ming Zhao,et al.  Cellular imaging of deep organ using two-photon Bessel light-sheet nonlinear structured illumination microscopy. , 2014, Biomedical optics express.

[15]  K. Dholakia,et al.  Exploiting multimode waveguides for pure fibre-based imaging , 2012, Nature Communications.

[16]  Satomi Teraoka,et al.  [Three Dimensional Display in Nuclear Medicine]. , 2015, Igaku butsuri : Nihon Igaku Butsuri Gakkai kikanshi = Japanese journal of medical physics : an official journal of Japan Society of Medical Physics.

[17]  Pierre Nassoy,et al.  Light-sheet microscopy in thick media using scanned Bessel beams and two-photon fluorescence excitation. , 2013, Optics express.

[18]  W. Denk,et al.  Two-photon imaging to a depth of 1000 microm in living brains by use of a Ti:Al2O3 regenerative amplifier. , 2003, Optics letters.

[19]  Colin J R Sheppard Pupil filters for generation of light sheets. , 2013, Optics express.

[20]  Jerome Mertz,et al.  Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection. , 2010, Journal of biomedical optics.

[21]  D N Payne,et al.  Mode conversion coefficients in optical fibers. , 1975, Applied optics.

[22]  David S. Koos,et al.  Deep and fast live imaging with two-photon scanned light-sheet microscopy , 2011, Nature Methods.

[23]  David Artigas,et al.  Image formation by linear and nonlinear digital scanned light-sheet fluorescence microscopy with Gaussian and Bessel beam profiles , 2012, Biomedical optics express.

[24]  T Čižmár,et al.  GPU accelerated toolbox for real-time beam-shaping in multimode fibres. , 2014, Optics express.

[25]  Silvio Bianchi,et al.  A multi-mode fiber probe for holographic micromanipulation and microscopy. , 2012, Lab on a chip.

[26]  Jonathan M. Taylor,et al.  3D adaptive optics in a light sheet microscope. , 2012, Optics express.

[27]  D. Ferrier,et al.  Cell proliferation dynamics in regeneration of the operculum head appendage in the annelid Pomatoceros lamarckii. , 2014, Journal of experimental zoology. Part B, Molecular and developmental evolution.

[28]  H. Sang,et al.  Myosin II-mediated cell shape changes and cell intercalation contribute to primitive streak formation , 2015, Nature Cell Biology.

[29]  V. Ntziachristos Going deeper than microscopy: the optical imaging frontier in biology , 2010, Nature Methods.

[30]  Kunal K. Ghosh,et al.  Advances in light microscopy for neuroscience. , 2009, Annual review of neuroscience.