SHG nanoprobes: Advancing harmonic imaging in biology

Second harmonic generating (SHG) nanoprobes have recently emerged as versatile and durable labels suitable for in vivo imaging, circumventing many of the inherent drawbacks encountered with classical fluorescent probes. Since their nanocrystalline structure lacks a central point of symmetry, they are capable of generating second harmonic signal under intense illumination – converting two photons into one photon of half the incident wavelength – and can be detected by conventional two‐photon microscopy. Because the optical signal of SHG nanoprobes is based on scattering, rather than absorption as in the case of fluorescent probes, they neither bleach nor blink, and the signal does not saturate with increasing illumination intensity. When SHG nanoprobes are used to image live tissue, the SHG signal can be detected with little background signal, and they are physiologically inert, showing excellent long‐term photostability. Because of their photophysical properties, SHG nanoprobes provide unique advantages for molecular imaging of living cells and tissues with unmatched sensitivity and temporal resolution.

[1]  D. Nikogosyan,et al.  Nonlinear Optical Crystals: A Complete Survey , 2005 .

[2]  T. Maiman Stimulated Optical Radiation in Ruby , 1960, Nature.

[3]  S. Hell,et al.  Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[4]  S. Brasselet,et al.  Balanced homodyne detection of second-harmonic generation from isolated subwavelength emitters , 2006 .

[5]  T. Basché Fluorescence intensity fluctuations of single atoms, molecules and nanoparticles , 1998 .

[6]  L. Svaasand,et al.  Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy. , 2000, Neoplasia.

[7]  Paul J Campagnola,et al.  Macromolecular structure of cellulose studied by second-harmonic generation imaging microscopy. , 2003, Optics letters.

[8]  F. V. van Veggel,et al.  Silica-coated Ln3+-Doped LaF3 nanoparticles as robust down- and upconverting biolabels. , 2006, Chemistry.

[9]  Rafael Yuste,et al.  Imaging membrane potential in dendritic spines. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Y. Mugnier,et al.  Polar Fe(IO3)3 nanocrystals as local probes for nonlinear microscopy , 2007 .

[11]  K. Eisenthal,et al.  Kinetics of molecular transport across a liposome bilayer , 1998 .

[12]  Shuming Nie,et al.  Re-examining the origins of spectral blinking in single-molecule and single-nanoparticle SERS. , 2006, Faraday discussions.

[13]  H. Tanke,et al.  Infrared up-converting phosphors for bioassays. , 2005, IEE proceedings. Nanobiotechnology.

[14]  A. Lipovskii,et al.  Hyper-Rayleigh scattering from BaTiO3 and PbTiO3 nanocrystals , 2009 .

[15]  May D. Wang,et al.  In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags , 2008, Nature Biotechnology.

[16]  W. Hübner,et al.  Nonlinear Mie scattering from spherical particles , 2004 .

[17]  Shaul Hanany,et al.  Comparison of the crossed and the Gregorian Mizuguchi-Dragone for wide-field millimeter-wave astronomy. , 2008, Applied optics.

[18]  William A Mohler,et al.  Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues. , 2002, Biophysical journal.

[19]  J. Roch,et al.  Coherent nonlinear emission from a single KTP nanoparticle with broadband femtosecond pulses. , 2009, Optics Express.

[20]  S. L. Mayo,et al.  A designed phenylalanyl-tRNA synthetase variant allows efficient in vivo incorporation of aryl ketone functionality into proteins. , 2002, Journal of the American Chemical Society.

[21]  Shiwei Wu,et al.  Non-blinking and photostable upconverted luminescence from single lanthanide-doped nanocrystals , 2009, Proceedings of the National Academy of Sciences.

[22]  Isaac Freund,et al.  Second harmonic generation in collagen , 1979 .

[23]  Thierry Gacoin,et al.  Photostable second-harmonic generation from a single KTiOPO4 nanocrystal for nonlinear microscopy. , 2008, Small.

[24]  P. Prasad,et al.  Zinc Oxide Nanocrystals for Non-resonant Nonlinear Optical Microscopy in Biology and Medicine. , 2008, The journal of physical chemistry. C, Nanomaterials and interfaces.

[25]  Michael Z. Lin,et al.  Selective labeling of proteins with chemical probes in living cells. , 2008, Physiology.

[26]  W. Denk,et al.  Two-photon laser scanning fluorescence microscopy. , 1990, Science.

[27]  Rafael Yuste,et al.  Second harmonic generation in neurons: electro-optic mechanism of membrane potential sensitivity. , 2007, Biophysical journal.

[28]  Peter J. Pauzauskie,et al.  Tunable nanowire nonlinear optical probe , 2007, Nature.

[29]  Demetri Psaltis,et al.  Three-dimensional harmonic holographic microcopy using nanoparticles as probes for cell imaging. , 2009, Optics express.

[30]  L Sacconi,et al.  Overcoming photodamage in second-harmonic generation microscopy: real-time optical recording of neuronal action potentials. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J. Pawley,et al.  Handbook of Biological Confocal Microscopy , 1990, Springer US.

[32]  Chen-Yuan Dong,et al.  Chemical enhancer induced changes in the mechanisms of transdermal delivery of zinc oxide nanoparticles. , 2009, Biomaterials.

[33]  Masato Yasuhara,et al.  Physicochemical Properties and Cellular Toxicity of Nanocrystal Quantum Dots Depend on Their Surface Modification , 2004 .

[34]  W. Webb,et al.  Molecular dynamics in living cells observed by fluorescence correlation spectroscopy with one- and two-photon excitation. , 1999, Biophysical journal.

[35]  M. Fejer,et al.  Observation of 99% pump depletion in single-pass second-harmonic generation in a periodically poled lithium niobate waveguide. , 2002, Optics letters.

[36]  M. Bruchez,et al.  Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots , 2003, Nature Biotechnology.

[37]  Demetri Psaltis,et al.  Second harmonic generating (SHG) nanoprobes: a new tool for biomedical imaging , 2009, BiOS.

[38]  M. Dahan,et al.  Imaging the lateral diffusion of membrane molecules with quantum dots , 2007, Nature Protocols.

[39]  P. Bourgine,et al.  Cell Lineage Reconstruction of Early Zebrafish Embryos Using Label-Free Nonlinear Microscopy , 2010, Science.

[40]  John Silcox,et al.  Non-blinking semiconductor nanocrystals , 2009, Nature.

[41]  Shuming Nie,et al.  Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry , 2007, Nature Protocols.

[42]  Anna-Katerina Hadjantonakis,et al.  Dynamic in vivo imaging and cell tracking using a histone fluorescent protein fusion in mice , 2004, BMC biotechnology.

[43]  D. Murphy Fundamentals of Light Microscopy and Electronic Imaging , 2001 .

[44]  C. C. Wang,et al.  Nonlinear optics. , 1966, Applied optics.

[45]  Steven R. Emory,et al.  Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering , 1997, Science.

[46]  George H Patterson,et al.  Photobleaching and photoactivation: following protein dynamics in living cells. , 2003, Nature cell biology.

[47]  M. J. Cormier,et al.  Primary structure of the Aequorea victoria green-fluorescent protein. , 1992, Gene.

[48]  Demetri Psaltis,et al.  Harmonic holography: a new holographic principle. , 2008, Applied optics.

[49]  C. Kimmel,et al.  Stages of embryonic development of the zebrafish , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[50]  M Deutsch,et al.  Connective tissue polarity. Optical second-harmonic microscopy, crossed-beam summation, and small-angle scattering in rat-tail tendon. , 1986, Biophysical journal.

[51]  J. Matthew Mauro,et al.  Long-term multiple color imaging of live cells using quantum dot bioconjugates , 2003, Nature Biotechnology.

[52]  J. Mertz,et al.  Second-harmonic generation by focused excitation of inhomogeneously distributed scatterers , 2001 .

[53]  Richard D. Schaller,et al.  Near-Field Imaging of Nonlinear Optical Mixing in Single Zinc Oxide Nanowires , 2002 .

[54]  B. Gates,et al.  Two-way photoswitching using one type of near-infrared light, upconverting nanoparticles, and changing only the light intensity. , 2010, Journal of the American Chemical Society.

[55]  V Lombardi,et al.  Probing myosin structural conformation in vivo by second-harmonic generation microscopy , 2010, Proceedings of the National Academy of Sciences.

[56]  Chi-Kuang Sun,et al.  A sub-100 fs self-starting Cr:forsterite laser generating 1.4 W output power. , 2010, Optics express.

[57]  Thomas Feurer,et al.  Nanodoublers as deep imaging markers for multi-photon microscopy. , 2009, Optics express.

[58]  J. G. Solé,et al.  Multicolour second harmonic generation by strontium barium niobate nanoparticles , 2009, Journal of Physics D: Applied Physics.

[59]  W B Amos,et al.  How the Confocal Laser Scanning Microscope entered Biological Research , 2003, Biology of the cell.

[60]  Leslie M Loew,et al.  Sensitivity of second harmonic generation from styryl dyes to transmembrane potential. , 2004, Biophysical journal.

[61]  M. Nirmal,et al.  Fluorescence intermittency in single cadmium selenide nanocrystals , 1996, Nature.

[62]  Michael D. Mason,et al.  Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. , 2006, Biophysical journal.

[63]  Naomi J. Halas,et al.  Nanoengineering of optical resonances , 1998 .

[64]  Michael Kasha,et al.  Characterization of electronic transitions in complex molecules , 1950 .

[65]  M. Bruchez,et al.  Long-term persistence and spectral blue shifting of quantum dots in vivo. , 2009, Nano letters.

[66]  S. Hell Far-Field Optical Nanoscopy , 2007, Science.

[67]  J. Lippincott-Schwartz,et al.  Imaging Intracellular Fluorescent Proteins at Nanometer Resolution , 2006, Science.

[68]  David A. Williams,et al.  Diffusion Dynamics of Glycine Receptors Revealed by Single – Quantum Dot Tracking , 2012 .

[69]  J Mertz,et al.  Coherent scattering in multi-harmonic light microscopy. , 2001, Biophysical journal.

[70]  A. Welch,et al.  A review of the optical properties of biological tissues , 1990 .

[71]  S. Bhatia,et al.  Probing the Cytotoxicity Of Semiconductor Quantum Dots. , 2004, Nano letters.

[72]  Michael J Rust,et al.  Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM) , 2006, Nature Methods.

[73]  Watt W Webb,et al.  Interpreting second-harmonic generation images of collagen I fibrils. , 2005, Biophysical journal.

[74]  J Mertz,et al.  Membrane imaging by simultaneous second-harmonic generation and two-photon microscopy. , 2000, Optics letters.

[75]  A. Menciassi,et al.  Preparation of stable dispersion of barium titanate nanoparticles: Potential applications in biomedicine. , 2010, Colloids and surfaces. B, Biointerfaces.

[76]  D. Psaltis,et al.  Nonlinear optical properties of core-shell nanocavities for enhanced second-harmonic generation. , 2010, Physical review letters.

[77]  Leonardo Sacconi,et al.  Optical recording of fast neuronal membrane potential transients in acute mammalian brain slices by second-harmonic generation microscopy. , 2005, Journal of neurophysiology.

[78]  P. Pantazis,et al.  Localized multiphoton photoactivation of paGFP in Drosophila wing imaginal discs. , 2007, Journal of biomedical optics.

[79]  R. Tsien,et al.  The Fluorescent Toolbox for Assessing Protein Location and Function , 2006, Science.

[80]  Brian Seed,et al.  Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation , 2003, Nature Medicine.

[81]  Igor V. Stiopkin,et al.  Experimental study of optical second-harmonic scattering from spherical nanoparticles , 2006 .

[82]  S. Hell,et al.  Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. , 1994, Optics letters.

[83]  Huan-Cheng Chang,et al.  Bright fluorescent nanodiamonds: no photobleaching and low cytotoxicity. , 2005, Journal of the American Chemical Society.

[84]  Richard L. Sutherland,et al.  Handbook of Nonlinear Optics , 1996 .

[85]  Hsiao-Yun Wu,et al.  Characterization and application of single fluorescent nanodiamonds as cellular biomarkers , 2007, Proceedings of the National Academy of Sciences.

[86]  J. Twamley,et al.  Observation and control of blinking nitrogen-vacancy centres in discrete nanodiamonds. , 2010, Nature nanotechnology.

[87]  Leslie M Loew,et al.  Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms , 2003, Nature Biotechnology.

[88]  Sanjiv S. Gambhir,et al.  Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy , 2009, Proceedings of the National Academy of Sciences.

[89]  Louis E. Brus,et al.  Surface Enhanced Raman Spectroscopy of Individual Rhodamine 6G Molecules on Large Ag Nanocrystals , 1999 .

[90]  Eric Betzig,et al.  Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues , 2010, Nature Methods.

[91]  Ralph Weissleder,et al.  Design and demonstration of a small-animal up-conversion imager. , 2008, Optics express.

[92]  S. Brasselet,et al.  Defocused imaging of second harmonic generation from a single nanocrystal. , 2007, Optics express.

[93]  John E. Sipe,et al.  Phenomenological treatment of surface second-harmonic generation , 1988 .

[94]  Y. Shen,et al.  Surface properties probed by second-harmonic and sum-frequency generation , 1989, Nature.

[95]  Nathan C Shaner,et al.  A guide to choosing fluorescent proteins , 2005, Nature Methods.

[96]  Koen Clays,et al.  Amphiphilic porphyrins for second harmonic generation imaging. , 2009, Journal of the American Chemical Society.

[97]  Tony F. Heinz,et al.  Spectroscopy of Molecular Monolayers by Resonant Second-Harmonic Generation , 1982 .

[98]  Huan-Cheng Chang,et al.  Mass production and dynamic imaging of fluorescent nanodiamonds. , 2008, Nature nanotechnology.

[99]  S. Fraser,et al.  Receptor-targeted co-transport of DNA and magnetic resonance contrast agents. , 1995, Chemistry & biology.

[100]  C. Peters,et al.  Generation of optical harmonics , 1961 .

[101]  Periklis Pantazis,et al.  Second harmonic generating (SHG) nanoprobes for in vivo imaging , 2010, Proceedings of the National Academy of Sciences.