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Zhang S L, Liu L W, Ren S, Li Z L, Zhao Y H et al. Recent advances in nonlinear optics for bio-imaging applications. Opto-Electron Adv 3, 200003 (2020). doi: 10.29026/oea.2020.200003
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Review Open Access
Recent advances in nonlinear optics for bio-imaging applications
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Abstract
Nonlinear optics, which is a subject for studying the interaction between intense light and materials, has great impact on various research fields. Since many structures in biological tissues exhibit strong nonlinear optical effects, nonlinear optics has been widely applied in biomedical studies. Especially in the aspect of bio-imaging, nonlinear optical techniques can provide rapid, label-free and chemically specific imaging of biological samples, which enable the investigation of biological processes and analysis of samples beyond other microscopy techniques. In this review, we focus on the introduction of nonlinear optical processes and their applications in bio-imaging as well as the recent advances in this filed. Our perspective of this field is also presented.-
Keywords:
- nonliner optics /
- microscopic imaging /
- bio-imaging /
- label-free /
- chemical specific
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References
[1] Shen Y R. The Principles of Nonlinear Optics (Wiley Press, New York, 1984). [2] Boyd R W. Nonlinear Optics (Academic Press, New York, 2007). [3] Agrawal G P. Applications of Nonlinear Fiber Optics (Academic Press, London, 2001). [4] Saleh B E A, Teich M C. Fundamentals of Photonics 2nd ed (Wiley, Hoboken, 2007). [5] Garmire E. Nonlinear optics in daily life. Opt Exp 21, 30532–30544 (2013). doi: 10.1364/OE.21.030532 [6] Chen L W, Zhou Y, Wu M X, Hong M H. Remote-mode microsphere nano-imaging: new boundaries for optical microscopes. Opto Electron Adv 1, 170001 (2018). [7] Liu Z X, Jiang M L, Hu Y L, Lin F, Shen B et al. Scanning cathodoluminescence microscopy: applications in semiconductor and metallic nanostructures. Opto-Electron Adv 1, 180007 (2018). [8] Franken P A, Hill A E, Peters C W, Weinreich G.Generation of optical harmonics. Phys Rev Lett 7, 118–119 (1961). doi: 10.1103/PhysRevLett.7.118 [9] Maiman T H. Optical and microwave-optical experiments in ruby. Phys Rev Lett 4, 564–566 (1960). doi: 10.1103/PhysRevLett.4.564 [10] Nikogosyan D N. Nonlinear Optical Crystals: A Complete Survey (Springer, New York, 2005). [11] Myers L E, Bosenberg W R. Periodically poled lithium niobate and quasi-phase-matched optical parametric oscillators. IEEE J Quantum Electron 33, 1663–1672 (1997). doi: 10.1109/3.631262 [12] Chen Q, Risk W P. Periodic poling of KTiOPO4 using an applied electric field. Electron Lett 30, 1516–1517 (1994). doi: 10.1049/el:19941019 [13] Karlsson H, Laurell F, Henriksson P, Arvidsson G.Frequency doubling in periodically poled RbTiOAsO4. Electron Lett 32, 556–557 (1996). doi: 10.1049/el:19960402 [14] Mizuuchi K, Yamamoto K. Generation of 340-nm light by frequency doubling of a laser diode in bulk periodically poled LiTaO3. Opt Lett 21, 107–109 (1996). doi: 10.1364/OL.21.000107 [15] Meyn J P, Fejer M M. Tunable ultraviolet radiation by second-harmonic generation in periodically poled lithium tantalate. Opt Lett 22, 1214–1216 (1997). doi: 10.1364/OL.22.001214 [16] Setzler S D, Schunemann P G, Pollak T M, Pomeranz L A, Missey M J. Advanced Solid-State Lasers, OSA Trends in Optics and Photonics Series. Washington DC: Optical Society of America, 1999: 676. [17] Meyn J P, Klein M E, Woll D, Wallenstein R, Rytz D.Periodically poled potassium niobate for second-harmonic generation at 463 nm. Opt Lett 24, 1154–1156 (1999). doi: 10.1364/OL.24.001154 [18] Johnson J C, Yan H Q, Schaller R D, Petersen P B, Yang P D et al.Near-field imaging of nonlinear optical mixing in single zinc oxide nanowires. Nano Lett 2, 279–283 (2002). doi: 10.1021/nl015686n [19] Nakayama Y, Pauzauskie P J, Radenovic A, Onorato R M, Saykally R J et al.Tunable nanowire nonlinear optical probe. Nature 447, 1098–1101 (2007). doi: 10.1038/nature05921 [20] Long J P, Simpkins B S, Rowenhorst D J, Pehrsson P E.Far-field imaging of optical second-harmonic generation in single GaN nanowires. Nano Lett 7, 831–836 (2007). doi: 10.1021/nl0624420 [21] Sanatinia R, Swillo M, Anand S. Surface second-harmonic generation from vertical GaP nanopillars. Nano Lett 12, 820–826 (2012). doi: 10.1021/nl203866y [22] Casadei A, Pecora E F, Trevino J, Forestiere C, Rüffer D et al.Photonic-plasmonic coupling of GaAs single nanowires to optical nanoantennas. Nano Lett 14, 2271–2278 (2014). doi: 10.1021/nl404253x [23] Bautista G, Mäkitalo J, Chen Y, Dhaka V, Grasso M et al.Second-harmonic generation imaging of semiconductor nanowires with focused vector beams. Nano Lett 15, 1564–1569 (2015). doi: 10.1021/nl503984b [24] Yin X B, Ye Z L, Chenet D A, Ye Y, O'Brien K et al.Edge nonlinear optics on a MoS2 atomic monolayer. Science 344, 488–490 (2014). doi: 10.1126/science.1250564 [25] Zhou X, Cheng J X, Zhou Y B, Cao H, Hong H et al.Strong second-harmonic generation in atomic layered GaSe. J Am Chem Soc 137, 7994–7997 (2015). doi: 10.1021/jacs.5b04305 [26] Handelman A, Lavrov S, Kudryavtsev A, Khatchatouriants A, Rosenberg Y et al. Nonlinear optical bioinspired peptide nanostructures. Adv Opt Mater 1, 875–884 (2013). doi: 10.1002/adom.201300282 [27] Semin S, Van Etteger A, Cattaneo L, Amdursky N, Kulyuk L et al.Strong thermo-induced single and two-photon green luminescence in self-organized peptide microtubes. Small 11, 1156–1160 (2015). doi: 10.1002/smll.201401602 [28] Farrar D, Ren K L, Cheng D, Kim S, Moon W et al.Permanent polarity and piezoelectricity of electrospun α-Helical Poly(α-Amino Acid) Fibers. Adv Mat 23, 3954–3958 (2011). doi: 10.1002/adma.201101733 [29] Zhang H H, Liao Q, Wang X D, Xu Z Z, Fu H B.Self-assembled organic hexagonal micro-prisms with high second harmonic generation efficiency for photonic devices. Nanoscale 7, 10186–10192 (2015). doi: 10.1039/C5NR00365B [30] Gibbs H M, Khitrova G, Peyghambarian N. Nonlinear Photonics (Springer, Berlin, 1990). [31] Philip R, Ravikanth M, Ravindra Kumar G. Studies of third order optical nonlinearity in iron (III) phthalocyanine μ-oxo dimers using picosecond four-wave mixing. Opt Comm 165, 91–97 (1999). doi: 10.1016/S0030-4018(99)00231-X [32] de la Torre G, Vázquez P, Agulló-López, Torres T.Role of structural factors in the nonlinear optical properties of phthalocyanines and related compounds. Chem Rev 104, 3723–3750 (2004). doi: 10.1021/cr030206t [33] Senge M O, Fazekas M, Notaras E G A, Blau W J, Zawadzka M et al.Nonlinear optical properties of porphyrins. Adv Mat 19, 2737–2774 (2007). doi: 10.1002/adma.200601850 [34] Xu J, Boyd R W, Fischer G L. Nonlinear optical materials. Reference Module in Materials Science and Materials Engineering, Elsevier (2016). [35] Wang K, Zhou J, Yuan L Y, Tao Y T, Chen J et al.Anisotropic third-order optical nonlinearity of a single ZnO micro/nanowire. Nano Lett 12, 833–838 (2012). doi: 10.1021/nl203884j [36] Zhang L C, Wang K, Liu Z, Yang G, Shen G Z et al.Two-photon pumped lasing in a single CdS microwire. Appl Phys Lett 102, 211915 (2013). doi: 10.1063/1.4809537 [37] Zhang C F, Zhang F, Xia T, Kumar N, Hahm J I et al.Low-threshold two-photon pumped ZnO nanowire lasers. Opt Express 17, 7893–7900 (2009). doi: 10.1364/OE.17.007893 [38] Chelnokov E V, Bityurin N.Two-photon pumped random laser in nanocrystalline ZnO. Appl Phy. Lett 89, 171119 (2006). doi: 10.1063/1.2370879 [39] HYPERLINK \l "_bookmark84" Zhang C, Zou C L, Yan Y L, Hao R, Sun F W et al. Two-photon pumped lasing in single-crystal organic nanowire exciton polariton resonators. J Am Chem Soc 133, 7276–7279 (2011). doi: 10.1021/ja200549v [40] Yu J C, Cui Y J, Xu H, Yang Y, Wang Z Y et al.Confinement of pyridinium hemicyanine dye within an anionic metal-organic framework for two-photon-pumped lasing. Nat Comm 4, 2719 (2013). doi: 10.1038/ncomms3719 [41] Helmchen F, Denk W. Deep tissue two-photon microscopy. Nat Methods 2, 932–940 (2005). doi: 10.1038/nmeth818 [42] Schenke-Layland K, Riemann I, Damour O, Stock U A, König K.Two-photon microscopes and in vivo multiphoton tomographs-Powerful diagnostic tools for tissue engineering and drug delivery. Adv Drug Deliv Rev 58, 878–896 (2006). doi: 10.1016/j.addr.2006.07.004 [43] Miller D R, Jarrett J W, Hassan A M, Dunn A K.Deep tissue imaging with multiphoton fluorescence microscopy. Curr Opin Biomed Eng 4, 32–39 (2017). doi: 10.1016/j.cobme.2017.09.004 [44] Denk W, Strickler J H, Webb W W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990). doi: 10.1126/science.2321027 [45] Piston D W, Kirby M S, Cheng H, Lederer W J, Webb W W.Two-photon-excitation fluorescence imaging of three-dimensional calcium-ion activity. Appl Opt 33, 662–669 (1994). doi: 10.1364/AO.33.000662 [46] Patterson G H, Knobel S M, Arkhammar P, Thastrup O, Piston D W.Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet β cells. Proc Natl Acad Sci USA 97, 5203–5207 (2000). doi: 10.1073/pnas.090098797 [47] Bennett B D, Jetton T L, Ying G T, Magnuson M A, Piston D W.Quantitative subcellular imaging of glucose metabolism within intact pancreatic islets. J Biol Chem 271, 3647–3651 (1996). doi: 10.1074/jbc.271.7.3647 [48] Huang S H, Heikal A A, Webb W W. Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein. Biophys J 82, 2811–2825 (2002). doi: 10.1016/S0006-3495(02)75621-X [49] Deyl Z, Macek K, Adam M, Vančíková.Studies on the chemical nature of elastin fluorescence. Biochimi Biophys Acta 625, 248–254 (1980). doi: 10.1016/0005-2795(80)90288-3 [50] Zipfel W R, Williams R M, Christie R, Nikitin A Y, Hyman B T et al.Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc Natl Acad Sci USA 100, 7075–7080 (2003). doi: 10.1073/pnas.0832308100 [51] Yu Q R, Heikal A A. Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level. J Photochem Photobiol B 95, 46–57 (2009). doi: 10.1016/j.jphotobiol.2008.12.010 [52] Kasischke K A, Lambert E M, Panepento B, Sun A, Gelbard H A et al.Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions. J Cereb Blood Flow Metab 31, 68–81 (2010). [53] Balu M, Mazhar A, Hayakawa C K, Mittal R, Krasieva T B et al.In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin. Biophys J 104, 258–267 (2013). doi: 10.1016/j.bpj.2012.11.3809 [54] Mansour A A, Gonçalves J T, Bloyd C W, Li H, Fernandes S et al.An in vivo model of functional and vascularized human brain organoids. Nat Biotechnol 36, 432–441 (2018). doi: 10.1038/nbt.4127 [55] Mei J, Huang Y H, Tian H. Progress and trends in AIE-based bioprobes: a brief overview. ACS Appl Mater Interfaces 10, 12217–12261 (2018). doi: 10.1021/acsami.7b14343 [56] Collot M, Fam T K, Ashokkumar P, Faklaris O, Galli T et al.Ultrabright and fluorogenic probes for multicolor imaging and tracking of lipid droplets in cells and tissues. J Am Chem Soc 140, 5401–5411 (2018). doi: 10.1021/jacs.7b12817 [57] Lou X D, Zhao Z J, Tang B Z. Organic dots based on AIEgens for two-photon fluorescence bioimaging. Small 12, 6430–6450 (2016). doi: 10.1002/smll.201600872 [58] Ding D, Goh C C, Feng G X, Zhao Z J, Liu J et al.Ultrabright organic dots with aggregation-induced emission characteristics for real-time two-photon intravital vasculature imaging. Adv Mat 25, 6083–6088 (2013). doi: 10.1002/adma.201301938 [59] Yi R X, Das P, Lin F R, Shen B L, Yang Z G et al.Fluorescence enhancement of small squaraine dye and its two-photon excited fluorescence in long-term near-infrared I & II bioimaging. Opt Express 27, 12360–12372 (2019). doi: 10.1364/OE.27.012360 [60] Wang H F, Huff T B, Zweifel D A, He W, Low P S et al. In vitro and in vivo two-photon luminescence imaging of single gold nanorods. Proc Natl Acad Sci USA 102, 15752–15756 (2005). doi: 10.1073/pnas.0504892102 [61] Rane T D, Armani A M. Two-photon microscopy analysis of gold nanoparticle uptake in 3D cell spheroids. PLoS One 11, e0167548 (2016). doi: 10.1371/journal.pone.0167548 [62] Tong L, Cobley C M, Chen J Y, Xia Y N, Cheng J X.Bright three-photon luminescence from gold/silver alloyed nanostructures for bioimaging with negligible photothermal toxicity. Angew Chem Int Ed 49, 3485–3488 (2010). doi: 10.1002/anie.201000440 [63] Au L, Zhang Q, Cobley C M, Gidding M, Schwartz A G et al.Quantifying the cellular uptake of antibody-conjugated Au nanocages by two-photon microscopy and inductively coupled plasma mass spectrometry. ACS Nano 4, 35–42 (2010). doi: 10.1021/nn901392m [64] Park Y I, Lee K T, Suh Y D, Hyeon T.Upconverting nanoparticles: a versatile platform for wide-field two-photon microscopy and multi-modal in vivo imaging. Chem Soc Rev 44, 1302–1317 (2015). doi: 10.1039/C4CS00173G [65] Yang S T, Cao L, Luo P G, Lu F S, Wang X et al.Carbon dots for optical imaging in vivo. J Am Chem Soc 131, 11308–11309 (2009). doi: 10.1021/ja904843x [66] Li D, Jing P T, Sun L H, An Y, Shan X Y et al.Near-infrared excitation/emission and multiphoton-induced fluorescence of carbon dots. Adv Mat 30, 1705913 (2018). doi: 10.1002/adma.201705913 [67] Wu C F, Chiu D T. Highly fluorescent semiconducting polymer dots for biology and medicine. Angew Chem Int Ed 52, 3086–3109 (2013). doi: 10.1002/anie.201205133 [68] Gao Y T, Feng G X, Jiang T, Goh C, Ng L et al.Biocompatible Nanoparticles based on diketo-pyrrolo-pyrrole (DPP) with aggregation-induced Red/NIR emission for in vivo two-photon fluorescence imaging. Adv Funct Mater 25, 2857–2866 (2015). doi: 10.1002/adfm.201500010 [69] Horton N G, Wang K, Kobat D, Clark C G, Wise F W et al. In vivo three-photon microscopy of subcortical structures within an intact mouse brain. Nat Photon 7 205–209 (2013). doi: 10.1038/nphoton.2012.336 [70] Ouzounov D G, Wang T Y, Wang M R, Feng D D, Horton N G et al. In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain. Nat Methods 14, 388–390 (2017). doi: 10.1038/nmeth.4183 [71] Wang T Y, Ouzounov D G, Wu C Y, Horton N G, Zhang B et al.Three-photon imaging of mouse brain structure and function through the intact skull. Nat Methods 15, 789–792 (2018). doi: 10.1038/s41592-018-0115-y [72] Rowlands C J, Park D, Bruns O T, Piatkevich K D, Fukumura D et al.Wide-field three-photon excitation in biological samples. Light Sci Appl 6, e16255 (2017). doi: 10.1038/lsa.2016.255 [73] Guesmi K, Abdeladim L, Tozer S, Mahou P, Kumamoto T et al.Dual-color deep-tissue three-photon microscopy with a multiband infrared laser. Light Sci Appl 7, 12 (2018). doi: 10.1038/s41377-018-0012-2 [74] Campagnola P J, Loew L M. Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms. Nat Biotechnol 21, 1356–1360 (2003). doi: 10.1038/nbt894 [75] Mohler W, Millard A C, Campagnola P J.Second harmonic generation imaging of endogenous structural proteins. Methods 29, 97–109 (2003). doi: 10.1016/S1046-2023(02)00292-X [76] Hellwarth R, Christensen P. Nonlinear optical microscopic examination of structure in polycrystalline ZnSe. Opt Comm 12, 318–322 (1974). doi: 10.1016/0030-4018(74)90024-8 [77] Sheppard C, Gannaway J, Kompfner R, Walsh D.The scanning harmonic optical microscope. IEEE J Quantum Electron 13, 912 (1977). [78] Freund I, Deutsch M, Sprecher A. Connective tissue polarity. Optical second-harmonic microscopy, crossed-beam summation, and small-angle scattering in rat-tail tendon. Biophys J 50, 693–712 (1986). doi: 10.1016/S0006-3495(86)83510-X [79] Lodish H, Berk A, Kaiser C A, Krieger M, Bretscher A et al. Molecular Cell Biology 7th ed (W. H. Freeman and Company, New York, 2013). [80] Bueno J M, Ávila F J, Artal P. Second harmonic generation microscopy: a tool for quantitative analysis of tissues, Microscopy and Analysis. London: IntechOpen, 2016: 19–27. [81] Campagnola P. Second harmonic generation imaging microscopy: applications to diseases diagnostic. Anal Chem 83, 3224–3231 (2011). doi: 10.1021/ac1032325 [82] Gusachenko I, Tran V, Houssen Y G, Allain J M, Schanne-Klein M C. Polarization-resolved second-harmonic generation in tendon upon mechanical stretching. Biophys J 102, 2220–2229 (2012). doi: 10.1016/j.bpj.2012.03.068 [83] Chen X Y, Nadiarynkh O, Plotnikov S, Campagnola P J.Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure. Nat Protoc 7, 654–669 (2012). doi: 10.1038/nprot.2012.009 [84] Lo W, Chen W L, Hsueh C M, Ghazaryan A A, Chen S J et al. Fast Fourier transform-based analysis of second-harmonic generation Image in keratoconic cornea. Invest Ophthalmol Vis Sci 53, 3501–3507 (2012). doi: 10.1167/iovs.10-6697 [85] Tan H Y, Chang Y L, Lo W, Hsueh C M, Chen W L et al.Characterizing the morphologic changes in collagen crosslinked–treated corneas by Fourier transform–second harmonic generation imaging. J Cat Refract Surg 39, 779–788 (2013). doi: 10.1016/j.jcrs.2012.11.036 [86] Provenzano P P, Eliceiri K W, Campbell J M, Inman D R, White J G et al. Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med 4, 38 (2006). doi: 10.1186/1741-7015-4-38 [87] Conklin M W, Eickhoff J C, Riching K M, Pehlke C A, Eliceiri K W et al.Aligned collagen is a prognostic signature for survival in human breast carcinoma. Am J Pathol 178, 1221–1232 (2011). doi: 10.1016/j.ajpath.2010.11.076 [88] Sahai E, Wyckoff J, Philippar U, Segall J E, Gertler F et al.Simultaneous imaging of GFP, CFP and collagen in tumors in vivo using multiphoton microscopy. BMC Biotechnol 5, 14 (2005). doi: 10.1186/1472-6750-5-14 [89] Kirkpatrick N D, Brewer M A, Utzinger U. Endogenous optical biomarkers of ovarian cancer evaluated with multiphoton microscopy. Cancer Epidemiol Biomarkers Prev 16, 2048–2057 (2007). doi: 10.1158/1055-9965.EPI-07-0009 [90] Nadiarnykh O, LaComb R B, Brewer M A, Campagnola P J.Alterations of the extracellular matrix in ovarian cancer studied by second harmonic generation imaging microscopy. BMC Cancer 10, 94 (2010). doi: 10.1186/1471-2407-10-94 [91] Lin S J, Jee S H, Kuo C J, Wu R J, Lin W C et al.Discrimination of basal cell carcinoma from normal dermal stroma by quantitative multiphoton imaging. Opt Lett 31, 2756–2758 (2006). doi: 10.1364/OL.31.002756 [92] Cicchi R, Massi D, Sestini S, Carli P, De Giorgi V et al.Multidimensional non-linear laser imaging of Basal Cell Carcinoma. Opt Express 15, 10135–10148 (2007). doi: 10.1364/OE.15.010135 [93] Dimitrow E, Ziemer M, Koehler M J, Norgauer J, König K et al. Sensitivity and specificity of multiphoton laser tomography for in vivo and ex vivo diagnosis of malignant melanoma. J Invest Dermatol 129, 1752–1758 (2009). doi: 10.1038/jid.2008.439 [94] Chen S Y, Chen S U, Wu H Y, Lee W J, Liao Y H et al. In vivo virtual biopsy of human skin by using noninvasive higher harmonic generation microscopy. IEEE J Sel Top Quant Electron 16, 478–492 (2010). doi: 10.1109/JSTQE.2009.2031987 [95] Sun W X, Chang S, Tai D C S, Tan N, Xiao G F et al. Nonlinear optical microscopy: use of second harmonic generation and two-photon microscopy for automated quantitative liver fibrosis studies. J Biomed Opt 13, 064010 (2008). doi: 10.1117/1.3041159 [96] Strupler M, Pena A M, Hernest M, Tharaux P L, Martin J L et al.Second harmonic imaging and scoring of collagen in fibrotic tissues. Opt Express 15, 4054–4065 (2007). doi: 10.1364/OE.15.004054 [97] Lacomb R, Nadiarnykh O, Campagnola P J. Quantitative Second Harmonic Generation imaging of the diseased state osteogenesis imperfecta: experiment and simulation. Biophys J 94, 4504–4514 (2008). doi: 10.1529/biophysj.107.114405 [98] Schenke-Layland K, Xie J S, Angelis E, Starcher B, Wu K J et al.Increased degradation of extracellular matrix structures of lacrimal glands implicated in the pathogenesis of Sjögren's syndrome. Matrix Biol 27, 53–66 (2008). [99] Lin S J, Wu R E, Tan H Y, Lo W, Lin W C et al. Evaluating cutaneous photoaging by use of multiphoton fluorescence and second-harmonic generation microscopy. Opt Lett 30, 2275–2277 (2005). doi: 10.1364/OL.30.002275 [100] Le T T, Langohr I, Locker M J, Sturek M, Cheng J X.Label-free molecular imaging of atherosclerotic lesions using multimodal nonlinear optical microscopy. J Biomed Opt 12, 054007 (2007). doi: 10.1117/1.2795437 [101] Kwon G P, Schroeder J L, Amar M J, Remaley A T, Balaban R S et al.Contribution of macromolecular structure to the retention of low-density lipoprotein at arterial branch points. Circulation 117, 2919–2927 (2008). doi: 10.1161/CIRCULATIONAHA.107.754614 [102] Kachynski A V, Pliss A, Kuzmin A N, Ohulchanskyy T Y, Baev A et al.Photodynamic therapy by in situ nonlinear photon conversion. Nat Photonics 8, 455–461 (2014). doi: 10.1038/nphoton.2014.90 [103] Bonacina L, Mugnier Y, Courvoisier F, Le Dantec R, Extermann J et al. Polar Fe(IO3)3 nanocrystals as local probes for nonlinear microscopy. Appl Phys B 87, 399–403 (2007). [104] Le X L, Zhou C Y, Slablab A, Chauvat D, Tard C et al. Photostable second-harmonic generation from a single KTiOPO4 nanocrystal for nonlinear microscopy. Small 4, 1332–1336 (2008). doi: 10.1002/smll.200701093 [105] Kachynski A V, Kuzmin A N, Nyk M, Roy I, Prasad P N. Zinc oxide nanocrystals for nonresonant nonlinear optical microscopy in biology and medicine. J Phys Chem C 112, 10721–10724 (2008). [106] Butet J, Bachelier G, Russier-Antoine I, Jonin C, Benichou E et al.Interference between selected dipoles and octupoles in the optical second-harmonic generation from spherical gold nanoparticles. Phys Rev Lett 105, 077401 (2010). doi: 10.1103/PhysRevLett.105.077401 [107] Butet J, Duboisset J, Bachelier G, Russier-Antoine I, Benichou E et al.Optical second harmonic generation of single metallic nanoparticles embedded in a homogeneous medium. Nano Lett 10, 1717–1721 (2010). doi: 10.1021/nl1000949 [108] Zavelani-Rossi M, Celebrano M, Biagioni P, Polli D, Finazzi M et al.Near-field second-harmonic generation in single gold nanoparticles. Appl Phys Lett 92, 093119 (2008). doi: 10.1063/1.2889450 [109] Hsieh C L, Grange R, Pu Y, Psaltis D.Bioconjugation of barium titanate nanocrystals with immunoglobulin G antibody for second harmonic radiation imaging probes. Biomaterials 31, 2272–2277 (2010). doi: 10.1016/j.biomaterials.2009.11.096 [110] Pantazis P, Maloney J, Wu D, Fraser S E.Second harmonic generating (SHG) nanoprobes for in vivo imaging. Proc Natl Acad Sci USA 107, 14535–14540 (2010). doi: 10.1073/pnas.1004748107 [111] Kuo T R, Wu C L, Hsu C T, Lo W, Chiang S J et al.Chemical enhancer induced changes in the mechanisms of transdermal delivery of zinc oxide nanoparticles. Biomaterials 30, 3002–3008 (2009). doi: 10.1016/j.biomaterials.2009.02.003 [112] Magouroux T, Extermann J, Hoffmann P, Mugnier Y, Dantec R L et al.High-speed tracking of murine cardiac stem cells by harmonic nanodoublers. Small 8, 2752–2756 (2012). [113] de Boer W D A M, Hirtz J J, Capretti A, Gregorkiewicz T, Izquierdo-Serra et al.Neuronal photoactivation through second-harmonic near-infrared absorption by gold nanoparticles. Light Sci Appl 7: 100. (2018) doi: 10.1038/s41377-018-0103-0 [114] Cheng J X, Xie X S. Green's function formulation for third-harmonic generation microscopy. J Opt Soc Am B 19, 1604–1610 (2002). doi: 10.1364/JOSAB.19.001604 [115] Sordillo L A, Pu Y, Pratavieira S, Budansky Y, Alfano R R.Deep optical imaging of tissue using the second and third near-infrared spectral windows. J. Biomed Opt 19, 056004 (2014). doi: 10.1117/1.JBO.19.5.056004 [116] Tsang T Y F. Optical third-harmonic generation at interfaces. Phys Rev A 52, 4116–4125 (1995). doi: 10.1103/PhysRevA.52.4116 [117] Barad Y, Eisenberg H, Horowitz M, Silberberg Y.Nonlinear scanning laser microscopy by third harmonic generation. Appl Phys Lett 70, 922–924 (1997). doi: 10.1063/1.118442 [118] Yelin D, Silberberg Y. Laser scanning third-harmonic-generation microscopy in biology. Opt Express 5, 169–175 (1999). doi: 10.1364/OE.5.000169 [119] Débarre D, Supatto W, Pena A M, Fabre A, Tordjmann T et al.Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy. Nat Methods 3, 47–53 (2006). doi: 10.1038/nmeth813 [120] Chen S Y, Hsieh C S, Chu S W, Lin C Y, Ko C Y et al.Noninvasive harmonics optical microscopy for long-term observation of embryonic nervous system development in vivo. J Biomed Opt 11, 054022 (2006). doi: 10.1117/1.2363369 [121] Pryke S R, Rollins L A, Griffith S C. Females use multiple mating and genetically loaded sperm competition to target compatible genes. Science 329, 964–967 (2010). doi: 10.1126/science.1192407 [122] Chu S W, Chen S Y, Tsai T H, Liu T M, Lin C Y et al.In vivo developmental biology study using noninvasive multi-harmonic generation microscopy. Opt Express 11, 3093–3099 (2003). doi: 10.1364/OE.11.003093 [123] Yildirim M, Durr N, Ben-Yakar A. Tripling the maximum imaging depth with third-harmonic generation microscopy. J. Biomed Opt 20, 096013 (2015). doi: 10.1117/1.JBO.20.9.096013 [124] Karunendiran A, Cisek R, Tokarz D, Barzda V, Stewart B A.Examination of Drosophila eye development with third harmonic generation microscopy. Biomed Opt Express 8, 4504–4513 (2017). doi: 10.1364/BOE.8.004504 [125] Tai S P, Lee W J, Shieh D B, Wu P C, Huang H Y et al. In vivo optical biopsy of hamster oral cavity with epi-third-harmonic-generation microscopy. Opt Express 14, 6178–6187 (2006). doi: 10.1364/OE.14.006178 [126] Tsai M R, Chen S Y, Shieh D B, Lou P J, Sun C K. In vivo optical virtual biopsy of human oral mucosa with harmonic generation microscopy. Biomed Opt Express 2, 2317–2328 (2011). doi: 10.1364/BOE.2.002317 [127] Lee W J, Lee C F, Chen S Y, Chen Y S, Sun C K.Virtual biopsy of rat tympanic membrane using higher harmonic generation microscopy. J. Biomed Opt 15, 046012 (2010). doi: 10.1117/1.3469848 [128] Genthial R, Beaurepaire E, Schanne-Klein M C, Peyrin F, Farlay D et al.Label-free imaging of bone multiscale porosity and interfaces using third-harmonic generation microscopy. Sci Rep 7, 3419 (2017). doi: 10.1038/s41598-017-03548-5 [129] Tokarz D, Cisek R, Wein M N, Turcotte R, Haase C et al.Intravital imaging of osteocytes in mouse calvaria using third harmonic generation microscopy. PLoS One 12, e0186846 (2017). doi: 10.1371/journal.pone.0186846 [130] Tsai C K, Wang T D, Lin J W, Hsu R B, Guo L Z et al.Virtual optical biopsy of human adipocytes with third harmonic generation microscopy. Biomed Opt Express 4, 178–186 (2013). doi: 10.1364/BOE.4.000178 [131] Weigelin B, Bakker G J, Friedl P. Intravital third harmonic generation microscopy of collective melanoma cell invasion: Principles of interface guidance and microvesicle dynamics. IntraVital 1, 32–43 (2012). doi: 10.4161/intv.21223 [132] Lee G G, Lin H H, Tsai M R, Chou S Y, Lee W J et al.Automatic cell segmentation and nuclear-to-cytoplasmic ratio analysis for third harmonic generated microscopy medical images. IEEE Trans Biomed Circuits Syst 7, 158–168 (2013). doi: 10.1109/TBCAS.2013.2253463 [133] Lee J H, Chen S Y, Yu C H, Chu S W, Wang L F et al.Noninvasive in vitro and in vivo assessment of epidermal hyperkeratosis and dermal fibrosis in atopic dermatitis. J Biomed Opt 14, 014008 (2009). doi: 10.1117/1.3077182 [134] Tai S P, Tsai T H, Lee W J, Shieh D B, Liao Y H et al.Optical biopsy of fixed human skin with backward-collected optical harmonics signals. Opt Express 13, 8231–8242 (2005). doi: 10.1364/OPEX.13.008231 [135] Tsai M R, Cheng Y H, Chen J S, Sheen Y S, Liao Y H et al.Differential diagnosis of nonmelanoma pigmented skin lesions based on harmonic generation microscopy. J Biomed Opt 19, 036001 (2014). doi: 10.1117/1.JBO.19.3.036001 [136] Wu P C, Hsieh T Y, Tsai Z U, Liu T M. In vivo quantification of the structural changes of collagens in a melanoma microenvironment with second and third harmonic generation microscopy. Sci Rep 5, 8879 (2015). doi: 10.1038/srep08879 [137] Adur J, Pelegati V B, De Thomaz A A, Baratti M O, Almeida D B et al.Optical biomarkers of serous and mucinous human ovarian tumor assessed with nonlinear optics microscopies. PLoS One 7, e47007 (2012). doi: 10.1371/journal.pone.0047007 [138] Kuzmin N V, Wesseling P, de Witt Hamer P C, Noske D P, Galgano G D et al.Third harmonic generation imaging for fast, label-free pathology of human brain tumors. Biomed Opt Express 7, 1889–1904 (2016). doi: 10.1364/BOE.7.001889 [139] Lim H, Sharoukhov D, Kassim I, Zhang Y Q, Salzer J L et al.Label-free imaging of Schwann cell myelination by third harmonic generation microscopy. Proc Natl Acad Sci USA111, 18025–18030 (2014). doi: 10.1073/pnas.1417820111 [140] Witte S, Negrean A, Lodder J C, de Kock C P J, Silva G T et al.Label-free live brain imaging and targeted patching with third-harmonic generation microscopy. Proc Natl Acad Sci USA108, 5970–5975 (2011). doi: 10.1073/pnas.1018743108 [141] Lanin A A, Chebotarev A S, Pochechuev M S, Kelmanson I V, Fedotov A B et al. Three-photon-resonance-enhanced third-harmonic generation for label-free deep-brain imaging: In search of a chemical contrast. J Raman Spectrosc 50, 1296–1302 (2019). doi: 10.1002/jrs.5566 [142] Kazarine A, Baakdah F, Gopal A A, Oyibo W, Georges E et al.Malaria detection by third-harmonic generation image scanning cytometry. Anal Chem 91, 2216–2223 (2019). doi: 10.1021/acs.analchem.8b04791 [143] van Huizen L M G, Kuzmin N V, Barbé E, van der Velde S, te Velde E A et al.Second and third harmonic generation microscopy visualizes key structural components in fresh unprocessed healthy human breast tissue. J Biophoton 12, e201800297 (2019). [144] Yelin D, Oron D, Thiberge S, Moses E, Silberberg Y.Multiphoton plasmon-resonance microscopy. Opt Express 11, 1385–1391 (2003). doi: 10.1364/OE.11.001385 [145] Lippitz M, van Dijk M A, Orrit M. Third-harmonic generation from single gold nanoparticles. Nano Lett 5, 799–802 (2005). doi: 10.1021/nl0502571 [146] Schwartz O, Oron D. Background-free third harmonic imaging of gold nanorods. Nano Lett 9, 4093–4097 (2009). doi: 10.1021/nl902305w [147] Liu T M, Tai S P, Yu C H, Wen Y C, Chu S W et al.Measuring plasmon-resonance enhanced third-harmonic χ(3) of Ag nanoparticles. Appl Phys Lett 89, 043122 (2006). doi: 10.1063/1.2240738 [148] Tai S P, Wu Y, Shieh D B, Chen L J, Lin K J et al.Molecular imaging of cancer cells using plasmon-resonant-enhanced third-harmonic-generation in silver nanoparticles. Adv Mat 19, 4520–4523 (2007). doi: 10.1002/adma.200602213 [149] Jung Y, Tong L, Tanaudommongkon A, Cheng J X, Yang C et al.In vitro and in vivo nonlinear optical imaging of silicon nanowires. Nano Lett 9, 2440–2444 (2009). doi: 10.1021/nl901143p [150] Chang C F, Chen H C, Chen M J, Liu W R, Hsieh W F et al.Direct backward third-harmonic generation in nanostructures. Opt Express 18, 7397–7406 (2010). doi: 10.1364/OE.18.007397 [151] Chen N, He Y, Su Y Y, Li X M, Huang Q et al.The cytotoxicity of cadmium-based quantum dots. Biomaterials 33, 1238–1244 (2012). doi: 10.1016/j.biomaterials.2011.10.070 [152] Dubreil L, Leroux I, Ledevin M, Schleder C, Lagalice L et al. Multi-harmonic imaging in the second near-infrared window of nanoparticle-labeled stem cells as a monitoring tool in tissue depth. ACS Nano 11, 6672–6681 (2017). doi: 10.1021/acsnano.7b00773 [153] Lee C W, Wu P C, Hsu I L, Liu T M, Chong W H et al.New templated ostwald ripening process of mesostructured FeOOH for third-harmonic generation bioimaging. Small 15, 1805086 (2019). doi: 10.1002/smll.201805086 [154] Terhune R W, Maker P D, Savage C M. Measurements of nonlinear light scattering. Phys Rev Lett 14, 681–684 (1965). doi: 10.1103/PhysRevLett.14.681 [155] Begley R F, Harvey A B, Byer R L. Coherent anti-stokes Raman spectroscopy. Appl Phys Lett 25, 387–390 (1974). doi: 10.1063/1.1655519 [156] Zumbusch A, Holtom G R, Xie X S. Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering. Phys Rev Lett 82, 4142–4145 (1999). doi: 10.1103/PhysRevLett.82.4142 [157] Cheng J X, Jia Y K, Zheng G F, Xie X S.Laser-scanning coherent anti-Stokes Raman scattering microscopy and applications to cell biology. Biophys J 83, 502–509 (2002). doi: 10.1016/S0006-3495(02)75186-2 [158] Volkmer A, Cheng J X, Xie X S. Vibrational imaging with high sensitivity via epidetected coherent anti-Stokes Raman scattering microscopy. Phys Rev Lett 87, 023901 (2001). doi: 10.1103/PhysRevLett.87.023901 [159] Cheng J X, Volkmer A, Book L D, Xie X S.Multiplex coherent anti-Stokes Raman scattering microspectroscopy and study of lipid vesicles. J Phys Chem B 106, 8493–8498 (2002). doi: 10.1021/jp025771z [160] Müller M, Schins J M. Imaging the thermodynamic state of lipid membranes with multiplex CARS microscopy. J Phys Chem B 106, 3715–3723 (2002). doi: 10.1021/jp014012y [161] Nan X L, Yang W Y, Xie X S. CARS microscopy lights up lipids in living cells. Biophoton Int 11, 44–47 (2004). [162] Rakic B, Sagan S M, Noestheden M, Bélanger S, Nan X L et al.Peroxisome proliferator–activated receptor α antagonism inhibits hepatitis C virus replication. Chem Biol 13, 23–30 (2006). doi: 10.1016/j.chembiol.2005.10.006 [163] Nan X L, Tonary A M, Stolow A, Xie X S, Pezacki J P et al.Intracellular imaging of HCV RNA and cellular lipids by using simultaneous two-photon fluorescence and coherent anti-Stokes Raman scattering microscopies. Chem Bio Chem 7, 1895–1897 (2006). doi: 10.1002/cbic.200600330 [164] Hellerer T, Axäng C, Brackmann C, Hillertz P, Pilon M et al. Monitoring of lipid storage in Caenorhabditis elegans using coherent anti-Stokes Raman scattering (CARS) microscopy. Proc Natl Acad Sci USA 104, 14658–14663 (2007). doi: 10.1073/pnas.0703594104 [165] Xie X S, Yu J, Yang W Y. Living cells as test tubes. Science 312, 228–230 (2006). doi: 10.1126/science.1127566 [166] Yen K, Le T T, Bansal A, Narasimhan S D, Cheng J X et al.A comparative study of fat storage quantitation in nematode Caenorhabditis elegans using label and label-free methods. PLoS One 5, e12810 (2010). doi: 10.1371/journal.pone.0012810 [167] Nan X L, Potma E O, Xie X S. Nonperturbative chemical imaging of organelle transport in living cells with coherent anti-Stokes Raman scattering microscopy. Biophys J 91, 728–735 (2006). doi: 10.1529/biophysj.105.074534 [168] Lyn R K, Kennedy D C, Stolow A, Ridsdale A, Pezacki J P et al.Dynamics of lipid droplets induced by the hepatitis C virus core protein. Biochem Biophys Res Commun 399, 518–524 (2010). doi: 10.1016/j.bbrc.2010.07.101 [169] Paar M, Jüngst C, Steiner N A, Magnes C, Sinner F et al.Remodeling of lipid droplets during lipolysis and growth in adipocytes. J Biol Chem 287, 11164–11173 (2012). doi: 10.1074/jbc.M111.316794 [170] Evans C L, Potma E O, Puoris'haag M, Côté D, Lin C P et al.Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy. Proc Natl Acad Sci USA 102, 16807–16812 (2005). doi: 10.1073/pnas.0508282102 [171] Breunig H G, Weinigel M, Bückle R, Kellner-Höfer M, Lademann J et al. Clinical coherent anti-Stokes Raman scattering and multiphoton tomography of human skin with a femtosecond laser and photonic crystal fiber. Laser Phys Lett 10, 025604 (2013). doi: 10.1088/1612-2011/10/2/025604 [172] Evans C L, Xie X S. Coherent anti-Stokes Raman Scattering microscopy: chemical imaging for biology and medicine. Annu Rev Anal Chem 1, 883–909 (2008). doi: 10.1146/annurev.anchem.1.031207.112754 [173] Toytman I, Cohn K, Smith T, Simanovskii D, Palanker D.Wide-field coherent anti-Stokes Raman scattering microscopy with non-phase-matching illumination. Opt Lett 32, 1941–1943 (2007). doi: 10.1364/OL.32.001941 [174] Brackmann C, Esguerra M, Olausson D, Delbro D, Krettek A et al.Coherent anti-Stokes Raman scattering microscopy of human smooth muscle cells in bioengineered tissue scaffolds. J Biomed Opt 16, 021115 (2011). doi: 10.1117/1.3534782 [175] Wang H W, Le T T, Cheng J X. Label-free imaging of arterial cells and extracellular matrix using a multimodal CARS microscope. Opt Comm 281, 1813–1822 (2008). doi: 10.1016/j.optcom.2007.07.067 [176] Wang H F, Fu Y, Zickmund P, Shi R, Cheng J X.Coherent anti-stokes Raman scattering imaging of axonal myelin in live spinal tissues. Biophys J 89, 581–591 (2005). doi: 10.1529/biophysj.105.061911 [177] Huff T B, Cheng J X. In vivo coherent anti-Stokes Raman scattering imaging of sciatic nerve tissue. J Microsc 225, 175–182 (2007). doi: 10.1111/j.1365-2818.2007.01729.x [178] Fu Y, Wang H F, Huff T B, Shi R, Cheng J X. Coherent anti-Stokes Raman scattering imaging of myelin degradation reveals a calcium-dependent pathway in lyso-PtdCho-induced demyelination. J Neurosci Res 85, 2870–2881 (2007). doi: 10.1002/jnr.21403 [179] Yookyung J, Ng J H, Keating C P, Senthil-Kumar P, Zhao J et al.Comprehensive evaluation of peripheral nerve regeneration in the acute healing phase using tissue clearing and optical microscopy in a rodent model. PLoS One 9, e94054 (2014). doi: 10.1371/journal.pone.0094054 [180] Evans C L, Xu X Y, Kesari S, Xie X S, Wong S T C et al.Chemically-selective imaging of brain structures with CARS microscopy. Opt Express 15, 12076–12087 (2007). doi: 10.1364/OE.15.012076 [181] Légaré F, Evans C L, Ganikhanov, Xie X S.Towards CARS endoscopy. Optics Express 14, 4427–4432 (2006). doi: 10.1364/OE.14.004427 [182] Camp Jr C H, Lee Y J, Heddleston J M, Hartshorn C M, Walker A R H et al.High-speed coherent Raman fingerprint imaging of biological tissues. Nat Photon 8, 627–634(2014). doi: 10.1038/nphoton.2014.145 [183] Bocklitz T W, Salah F S, Vogler N, Heuke S, Chernavskaia O et al.Pseudo-HE images derived from CARS/TPEF/SHG multimodal imaging in combination with Raman-spectroscopy as a pathological screening tool. BMC Cancer 16, 534 (2016). doi: 10.1186/s12885-016-2520-x [184] Petersen D, Mavarani L, Niedieker D, Freier E, Tannapfel A et al.Virtual staining of colon cancer tissue by label-free Raman micro-spectroscopy. Analyst 142, 1207–1215 (2017). doi: 10.1039/C6AN02072K [185] Galli R, Uckermann O, Temme A, Leipnitz E, Meinhardt M et al. Assessing the efficacy of coherent anti-Stokes Raman scattering microscopy for the detection of infiltrating glioblastoma in fresh brain samples. J Biophoton 10, 404–414 (2017). doi: 10.1002/jbio.201500323 [186] Karuna A, Masia F, Wiltshire M, Errington R, Langbein W.Label-free volumetric quantitative imaging of the human somatic cell division by hyperspectral coherent anti-Stokes Raman scattering. Anal Chem 91, 2813–2821 (2019). doi: 10.1021/acs.analchem.8b04706 [187] Niedieker D, Grosserüschkamp F, Schreiner A, Barkovits K, Kötting C et al.Label-free identification of myopathological features with coherent anti-Stokes Raman scattering. Muscle Nerve 58, 456–459 (2018). doi: 10.1002/mus.26140 [188] Hirose K, Fukushima S, Fukushima T, Niioka H, Hashimoto M.Invited Article: Label-free nerve imaging with a coherent anti-Stokes Raman scattering rigid endoscope using two optical fibers for laser delivery. APL Photon 3, 092407 (2018). doi: 10.1063/1.5031817 [189] Kang E, Wang H F, Kwon I K, Robinson J, Cheng J X.In situ visualization of paclitaxel distribution and release by coherent anti-Stokes Raman scattering microscopy. Anal Chem 78, 8036–8043 (2006). doi: 10.1021/ac061218s [190] Hartshorn C M, Lee Y J, Camp Jr C H, Liu Z, Heddleston J et al.Multicomponent chemical imaging of pharmaceutical solid dosage forms with broadband CARS microscopy. Anal Chem 85, 8102–8111 (2013). doi: 10.1021/ac400671p [191] Fussell A L, Grasmeijer F, Frijlink H W, de Boer A H, Offerhaus H L. CARS microscopy as a tool for studying the distribution of micronised drugs in adhesive mixtures for inhalation. J Raman Spectrosc 45, 495–500 (2014). doi: 10.1002/jrs.4515 [192] Tong L, Lu Y H, Lee R J, Cheng J X.Imaging receptor-mediated endocytosis with a polymeric nanoparticle-based coherent anti-Stokes Raman scattering probe. J Phys Chem B 111, 9980–9985 (2007). doi: 10.1021/jp073478z [193] Xu P S, Gullotti E, Tong L, Highley C B, Errabelli D R et al.Intracellular drug delivery by poly(lactic-co-glycolic acid) nanoparticles, revisited. Mol Pharm 6, 190–201 (2009). doi: 10.1021/mp800137z [194] Garrett N L, Lalatsa A, Begley D, Mihoreanu L, Uchegbu I F et al.Label-free imaging of polymeric nanomedicines using coherent anti-stokes Raman scattering microscopy. J Raman Spectrosc 43, 681–688 (2012). doi: 10.1002/jrs.3170 [195] Darville N, Saarinen J, Isomäki A, Khriachtchev L, Cleeren D et al. Multimodal non-linear optical imaging for the investigation of drug nano-/microcrystal–cell interactions. Eur J Pharm Biopharm 96, 338–348 (2015). doi: 10.1016/j.ejpb.2015.09.003 [196] Freudiger C W, Min W, Saar B G, Lu S J, Holtom G R et al.Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy. Science 322, 1857–1861 (2008). doi: 10.1126/science.1165758 [197] Ozeki Y, Dake F, Kajiyama S, Fukui K, Itoh K. Analysis and experimental assessment of the sensitivity of stimulated Raman scattering microscopy. Opt Express 17, 3651–3658 (2009). doi: 10.1364/OE.17.003651 [198] Nandakumar P, Kovalev A, Volkmer A.Vibrational imaging based on stimulated Raman scattering microscopy. New J Phys 11, 033026 (2009). doi: 10.1088/1367-2630/11/3/033026 [199] Zhang D L, Slipchenko M N, Cheng J X. Highly sensitive vibrational imaging by femtosecond pulse stimulated Raman loss. J Phys Chem Lett 2, 1248–1253 (2011). doi: 10.1021/jz200516n [200] Andresen E R, Berto P, Rigneault H. Stimulated Raman scattering microscopy by spectral focusing and fiber-generated soliton as Stokes pulse. Opt Lett 36, 2387–2389 (2011). doi: 10.1364/OL.36.002387 [201] Beier H T, Noojin G D, Rockwell B A. Stimulated Raman scattering using a single femtosecond oscillator with flexibility for imaging and spectral applications. Opt Express 19, 18885–18892 (2011). doi: 10.1364/OE.19.018885 [202] Slipchenko M N, Oglesbee R A, Zhang D L, Wu W, Cheng J X.Heterodyne detected nonlinear optical imaging in a lock-in free manner. J Biophoton 5, 801–807 (2012). doi: 10.1002/jbio.201200005 [203] Cheng J X, Xie X S, Vibrational spectroscopic imaging of living systems: An emerging platform for biology and medicine. Science 350, aaa8870 (2015). doi: 10.1126/science.aaa8870 [204] Woodbury E J, Ng W K. Ruby laser operation in near IR. Proc Inst Radio Eng 50, 2367 (1962). [205] Owyoung A, Jones E D. Stimulated Raman spectroscopy using low-power cw lasers. Opt Lett 1, 152–154 (1977). doi: 10.1364/OL.1.000152 [206] Ploetz E, Laimgruber S, Berner S, Zinth W, Gilch P.Femtosecond stimulated Raman microscopy. Appl Phys B 87, 389–393 (2007). doi: 10.1007/s00340-007-2630-x [207] Wang M C, Min W, Freudiger C W, Ruvkun G, Xie X S.RNAi screening for fat regulatory genes with SRS microscopy. Nat Methods 8, 135–138 (2011). doi: 10.1038/nmeth.1556 [208] Dou W, Zhang D L, Jung Y, Cheng J X, Umulis D M.Label-free imaging of lipid-droplet intracellular motion in early Drosophila embryos using femtosecond-stimulated Raman loss microscopy. Biophys J 102, 1666–1675 (2012). doi: 10.1016/j.bpj.2012.01.057 [209] Wang P, Liu B, Zhang D L, Belew M Y, Tissenbaum H A et al.Imaging lipid metabolism in live Caenorhabditis elegans using fingerprint vibrations. Angew Chem Int Ed 53, 11787–11792 (2014). doi: 10.1002/anie.201406029 [210] Hu C R, Zhang D L, Slipchenko M N, Cheng J X, Hu B.Label-free real-time imaging of myelination in the Xenopus laevis tadpole by in vivo stimulated Raman scattering microscopy. J Biomed Opt 19, 086005 (2014). doi: 10.1117/1.JBO.19.8.086005 [211] Freudiger C W, Pfannl R, Orringer D A, Saar B G, Ji M B et al. Multicolored stain-free histopathology with coherent Raman imaging. Lab Invest 92, 1492–1502 (2012). doi: 10.1038/labinvest.2012.109 [212] Lu F K, Ji M B, Fu D, Ni X H, Freudiger C W et al.Multicolor stimulated Raman scattering (SRS) microscopy. Mol Phys 110, 1927–1932 (2012). doi: 10.1080/00268976.2012.695028 [213] Lu F K, Basu S, Igras V, Hoang M P, Ji M B et al.Label-free DNA imaging in vivo with stimulated Raman scattering microscopy. Proc Natl Acad Sci USA 112, 11624–11629 (2015). doi: 10.1073/pnas.1515121112 [214] Yue S H, Li J J, Lee S Y, Lee H J, Shao T et al.Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab 19, 393–406 (2014). doi: 10.1016/j.cmet.2014.01.019 [215] Wang P, Li J J, Wang P, Hu C R, Zhang D L et al.Label-free quantitative imaging of cholesterol in intact tissues by hyperspectral stimulated raman scattering microscopy. Angew Chem Int Ed 52, 13042–13046 (2013). doi: 10.1002/anie.201306234 [216] Li J J, Condello S, Thomes-Pepin J, Ma X X, Xia Y et al.Lipid desaturation is a metabolic marker and therapeutic target of ovarian cancer stem cells. Cell Stem Cell 20, 303–314. (2017). doi: 10.1016/j.stem.2016.11.004 [217] Mittal R, Balu M, Krasieva T, Potma E O, Elkeeb L et al.Evaluation of stimulated Raman scattering microscopy for identifying squamous cell carcinoma in human skin. Lasers Surg Med 45, 496–502 (2013). [218] Ji M B, Orringer D A, Freudiger C W, Ramkissoon S, Liu X H et al.Rapid, label-free detection of brain tumors with stimulated Raman scattering microscopy. Sci Transl Med 5, 201ra119 (2013). [219] Jermyn M, Mok K, Mercier J, Desroches J, Pichette J et al.Intraoperative brain cancer detection with Raman spectroscopy in humans. Sci Transl Med 7, 274ra19 (2015). doi: 10.1126/scitranslmed.aaa2384 [220] Ji M B, Arbel M, Zhang L L, Freudiger C W, Hou S S et al.Label-free imaging of amyloid plaques in Alzheimer's disease with stimulated Raman scattering microscopy. Sci Adv 4, eaat7715 (2018). doi: 10.1126/sciadv.aat7715 [221] Yan S, Cui S S, Ke K, Zhao B X, Liu X L et al.Hyperspectral stimulated Raman scattering microscopy unravels aberrant accumulation of saturated fat in human liver cancer. Anal Chem 90, 6362–6366 (2018). doi: 10.1021/acs.analchem.8b01312 [222] Wei L, Yu Y, Shen Y H, Wang M C, Min W.Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy. Proc Natl Acad Sci USA 110, 11226–11231 (2013). doi: 10.1073/pnas.1303768110 [223] Li J J, Cheng J X. Direct visualization of de novo lipogenesis in single living cells. Sci Rep 4, 6807 (2014). [224] Shen Y H, Xu F, Wei L, Hu F H, Min W.Live-cell quantitative imaging of proteome degradation by stimulated Raman scattering. Angew Chem Int Ed 53, 5596–5599 (2014). doi: 10.1002/anie.201310725 [225] Li X S, Li Y, Jiang M J, Wu W J, He S C et al.Quantitative imaging of lipid synthesis and lipolysis dynamics in Caenorhabditis elegans by stimulated Raman scattering microscopy. Anal Chem 91, 2279–2287 (2019). doi: 10.1021/acs.analchem.8b04875 [226] Slipchenko M N, Chen H T, Ely D R, Jung Y, Carvajal M T et al.Vibrational imaging of tablets by epi-detected stimulated Raman scattering microscopy. Analyst 135, 2613–2619 (2010). doi: 10.1039/c0an00252f [227] Fu D, Zhou J, Zhu W J S, Manley P W, Wang Y K et al.Imaging the intracellular distribution of tyrosine kinase inhibitors in living cells with quantitative hyperspectral stimulated Raman scattering. Nat Chem 6, 614–622 (2014). doi: 10.1038/nchem.1961 [228] Chiu W S, Belsey N A, Garrett N L, Moger J, Delgado-Charro M B et al.Molecular diffusion in the human nail measured by stimulated Raman scattering microscopy. Proc Natl Acad Sci USA 112, 7725–7730 (2015). [229] Wei L, Min W. Pump-probe optical microscopy for imaging nonfluorescent chromophores. Anal Bioanal Chem 403, 2197–2202 (2012). doi: 10.1007/s00216-012-5890-1 [230] Fischer M C, Wilson J W, Robles F E, Warren W S.Invited Review Article: Pump-probe microscopy. Rev Sci Instrum 87, 031101 (2016). doi: 10.1063/1.4943211 [231] Dong P T, Chen J X. Pump-probe microscopy: theory, instrumentation, and application. Spectroscopy 32, 24–36 (2017). [232] Dong C Y, So P T, French T, Gratton E.Fluorescence lifetime imaging by asynchronous pump-probe microscopy. Biophys J 69, 2234–2242 (1995). doi: 10.1016/S0006-3495(95)80148-7 [233] Fu D, Ye T, Matthews T E, Yurtsever G, Warren Sr W S.Two-color, two-photon, and excited-state absorption microscopy. J Biomed Opt 12, 054004 (2007). doi: 10.1117/1.2780173 [234] Dan F, Ye T, Matthews T, Chen B J, Yurtserver G et al.High-resolution in vivo imaging of blood vessels without labeling. Opt Lett 32, 2641–2643 (2007). doi: 10.1364/OL.32.002641 [235] Min W, Lu S J, Chong S S, Roy R, Holtom G R et al.Imaging chromophores with undetectable fluorescence by stimulated emission microscopy. Nature 461, 1105–1109 (2009). doi: 10.1038/nature08438 [236] Piletic I R, Matthews T E, Warren W S. Probing near-infrared photorelaxation pathways in eumelanins and pheomelanins. J Phys Chem A 114, 11483–11491 (2010). doi: 10.1021/jp103608d [237] Matthews T E, Wilson J W, Degan S, Simpson M J, Jin J Y et al. In vivo and ex vivo epi-mode pump-probe imaging of melanin and microvasculature. Biomed Opt Express 2, 1576–1583 (2011). doi: 10.1364/BOE.2.001576 [238] Robles F E, Deb S, Wilson J W, Gainey C S, Selim M A et al.Pump-probe imaging of pigmented cutaneous melanoma primary lesions gives insight into metastatic potential. Biomed Opt Express6, 3631–3645 (2015). doi: 10.1364/BOE.6.003631 [239] Chen A J, Yuan X J, Li J J, Dong P T, Hamza I et al.Label-free imaging of heme dynamics in living organisms by transient absorption microscopy. Anal Chem 90, 3395–3401 (2018). doi: 10.1021/acs.analchem.7b05046 [240] Dong P T, Lin H N, Huang K C, Cheng J X.Label-free quantitation of glycated hemoglobin in single red blood cells by transient absorption microscopy and phasor analysis. Sci Adv 5, eaav0561 (2019). doi: 10.1126/sciadv.aav0561 [241] Tong L, Liu Y X, Dolash B D, Jung Y, Slipchenko M N et al. Label-free imaging of semiconducting and metallic carbon nanotubes in cells and mice using transient absorption microscopy. Nat Nanotechnol 7, 56–61 (2012). [242] Chen T, Lu F, Streets A M, Fei P, Quan J M et al. Optical imaging of non-fluorescent nanodiamonds in live cells using transient absorption microscopy. Nanoscale 5, 4701–4705 (2013). doi: 10.1039/c3nr00308f [243] Chen T, Chen S H, Zhou J H, Liang D H, Chen X Y et al. Transient absorption microscopy of gold nanorods as spectrally orthogonal labels in live cells. Nanoscale 6, 10536–10539 (2014). doi: 10.1039/C4NR03413A [244] Li J J, Zhang W X, Chung T F, Slipchenko M N et al. Highly sensitive transient absorption imaging of graphene and graphene oxide in living cells and circulating blood. Sci Rep 5, 12394 (2015). doi: 10.1038/srep12394 [245] Liao C S, Slipchenko M N, Wang P, Li J J, Lee S Y et al. Microsecond scale vibrational spectroscopic imaging by multiplex stimulated Raman scattering microscopy. Light Sci Appl 4, e265 (2015). doi: 10.1038/lsa.2015.38 -
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Zhang S L, Liu L W, Ren S, Li Z L, Zhao Y H et al. Recent advances in nonlinear optics for bio-imaging applications. Opto-Electron Adv 3, 200003 (2020). doi: 10.29026/oea.2020.200003
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Figure 1.
Typical examples of nonlinear optics processes and applications.
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Figure 2.
Main nonlinear optical modalities applied to bioimaging.
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Figure 3.
Energy diagrams of nonlinear optical processes employed for the bio-imaging.
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Figure 4.
Two-photon excited fluorescence imaging of vasculature and neuron in vivo.
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Figure 5.
Second harmonic generation imaging of the collagen tissues.
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Figure 6.
Third harmonic generation microscopic imaging of the tissues in vivo.
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Figure 7.
Coherent anti-Stokes Raman scattering imaging of tissues with CH2 contrast.
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Figure 8.
Stimulated Raman scattering imaging of biological samples.
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Figure 9.
Transient absorption imaging of heme granule dynamics in C. elegans.
