Flexible minimally invasive coherent anti-Stokes Raman spectroscopy (CARS) measurement method with tapered optical fiber probe for single-cell application

1.
School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin, 300072, China
2.
Key Laboratory of Opto-Electronics Information Technology, Ministry of Education, Tianjin University, Tianjin, 300072, China
3.
Tianjin Optical Fiber Sensing Engineering Center, Institute of Optical Fiber Sensing of Tianjin University, Tianjin University, Tianjin, 300072, China

Funds: This work was supported by the National Natural Science Foundation of China (NO. 61735011), National Key Scientific Instrument and Equipment Development Projects of China (NO. 2013YQ030915), State Key Laboratory of Information Photonics and Optical Communications (NO. 2021KFKT006), Tianjin Talent Development Special Plan for High Level Innovation and Entrepreneurship Team, and the first rank of Tianjin 131 Innovation Talent Development Program.

摘要

- /
- /
- /
Abstract: We proposed and demonstrated a flexible, endoscopic, and minimally invasive coherent anti-Raman Stokes scattering (CARS) measurement method for single-cell application, employing a tapered optical fiber probe. A few-mode fiber (FMF), whose generated four-wave mixing band is out of CARS signals, was selected to fabricate tapered optical fiber probes, deliver CARS excitation pulses, and collect CARS signals. The adiabatic tapered fiber probe with a diameter of 11.61 μm can focus CARS excitation lights without mismatch at the focal point. The measurements for proof-of-concept were made with methanol, ethanol, cyclohexane, and acetone injected into simulated cells. The experimental results show that the tapered optical fiber probe can detect carbon-hydrogen (C–H) bond-rich substances and their concentration. To our best knowledge, this optical fiber probe provides the minimum size among probes for detecting CARS signals. These results pave the way for minimally invasive live-cell detection in the future.
- Nonlinear optics /
- CARS /
- Tapered optical fiber probe /
- Raman scattering

HTML全文

参考文献(35)

[1]	Kellner-Weibel G, et al. Crystallization of Free Cholesterol in Model Macrophage Foam Cells. Atertio Thromb Vasc Biol. 1999;19:1891–8. https://doi.org/10.1161/01.ATV.19.8.1891.
[2]	Yue S, et al. Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab. 2014;19:393–406. https://doi.org/10.1016/j.cmet.2014.01.019.
[3]	Zumbusch A, Holtom GR, Xie XS. Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering. Phys Rev Lett. 1999;82:4142. https://doi.org/10.1103/PhysRevLett.82.4142.
[4]	Cheng JX, Xie XS. Coherent anti-Stokes Raman scattering microscopy: instrumentation, theory, and applications. J Phys Chem B. 2004;108:827–40. https://doi.org/10.1021/jp035693v.
[5]	Yue S, Cheng JX. Deciphering single cell metabolism by coherent Raman scattering microscopy. Curr Opin Chem Biol. 2016;33:46–57. https://doi.org/10.1016/j.cbpa.2016.05.016.
[6]	Lee YJ, et al. Quantitative, label-free characterization of stem cell differentiation at the single-cell level by broadband coherent anti-Stokes Raman scattering microscopy. Tissue Eng, Part C. 2014;20:562–9. https://doi.org/10.1089/ten.tec.2013.0472.
[7]	Di Napoli C, et al. Quantitative spatiotemporal chemical profiling of individual lipid droplets by hyperspectral CARS microscopy in living human adipose-derived stem cells. Anal Chem. 2016;88:3677–85. https://doi.org/10.1021/acs.analchem.5b04468.
[8]	Hofemeier AD, et al. Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells. Sci Rep. 2016;6:26716. https://doi.org/10.1038/srep26716.
[9]	Capitaine E, et al. Fast epi-detected broadband multiplex CARS and SHG imaging of mouse skull cells. Biomed Opt Express. 2018;9:245–53.
[10]	Untracht GR, Karnowski K, Sampson DD. Imaging the small with the small: Prospects for photonics in micro-endomicroscopy for minimally invasive cellular-resolution bioimaging. APL Photonics. 2021;6: 060901.
[11]	Wang H, Huff TB, Cheng JX. Coherent anti-Stokes Raman scattering imaging with a laser source delivered by a photonic crystal fiber. Opt Lett. 2006;31:1417–9. https://doi.org/10.1364/OL.31.001417.
[12]	Balu M, Liu GJ, Chen ZP, Tromberg BJ, Potma EO. Fiber delivered probe for efficient CARS imaging of tissues. Opt Express. 2010;18:2380–8. https://doi.org/10.1364/OE.18.002380.
[13]	Smith B, et al. Portable, miniaturized, fibre delivered, multimodal CARS exoscope. Opt Express. 2013;21:17161–75. https://doi.org/10.1364/OE.21.017161.
[14]	Chen X, Xu X, McCormick DT, Wong K, Wong ST. Multimodal nonlinear endo-microscopy probe design for high resolution, label-free intraoperative imaging. Biomed Opt Express. 2015;6:2283–93. https://doi.org/10.1364/BOE.6.002283.
[15]	Lukić A, et al. Fiber probe for nonlinear imaging applications. J Biophotonics. 2016;9:138–43.
[16]	Lukic A, et al. Endoscopic fiber probe for nonlinear spectroscopic imaging. Optica. 2017;4:496–501. https://doi.org/10.1364/OPTICA.4.000496.
[17]	Kim SH, et al. Multiplex coherent anti-stokes Raman spectroscopy images intact atheromatous lesions and concomitantly identifies distinct chemical profiles of atherosclerotic lipids. Circul Res. 2010;106:1332–41. https://doi.org/10.1161/CIRCRESAHA.109.208678.
[18]	Lombardini, A. et al. High-resolution multimodal flexible coherent Raman endoscope. Light Sci Appl. 2018;7:1–8. https://doi.org/10.1038/s41377-018-0003-3.
[19]	Wang J, et al. SERS-active fiber tip for intracellular and extracellular pH sensing in living single cells. Sens Actuators B: Chem. 2019;290:527–34. https://doi.org/10.1016/j.snb.2019.03.149.
[20]	Yang Q, et al. Fiber-optic-based micro-probe using hexagonal 1-in-6 fiber configuration for intracellular single-cell pH measurement. Anal Chem. 2015;87:7171–9. https://doi.org/10.1021/acs.analchem.5b01040.
[21]	Kasili PM, Song JM, Vo-Dinh T. Optical sensor for the detection of caspase-9 activity in a single cell. J Am Chem Soc. 2004;126:2799–806. https://doi.org/10.1021/ja037388t.
[22]	Liang F, et al. Direct tracking of amyloid and tau dynamics in neuroblastoma cells using nanoplasmonic fiber tip probes. Nano Lett. 2016;16:3989–94. https://doi.org/10.1021/acs.nanolett.6b00320.
[23]	Zheng XT, Yang HB, Li CM. Optical detection of single cell lactate release for cancer metabolic analysis. Anal Chem. 2010;82:5082–7. https://doi.org/10.1021/ac100074n.
[24]	Liu Z, Guo C, Yang J, Yuan L. Tapered fiber optical tweezers for microscopic particle trapping: fabrication and application. Opt Express. 2006;14:12510–6. https://doi.org/10.1364/OE.14.012510.
[25]	Cole R, Slepkov A. Interplay of pulse bandwidth and spectral resolution in spectral-focusing CARS microscopy. JOSA B. 2018;35:842–50. https://doi.org/10.1364/JOSAB.35.000842.
[26]	Wang Z, et al. Coherent anti-Stokes Raman scattering microscopy imaging with suppression of four-wave mixing in optical fibers. Opt Express. 2011;19:7960–70. https://doi.org/10.1364/OE.19.007960.
[27]	Wang Z, et al. Use of multimode optical fibers for fiber-based coherent anti-Stokes Raman scattering microendoscopy imaging. Opt Lett. 2011;36:2967–9. https://doi.org/10.1364/OL.36.002967.
[28]	Kipcak A, Senberber F, Derun EM, Piskin S. Evaluation of the magnesium wastes with boron oxide in magnesium borate synthesis. J Mater Metall Eng. 2012;6:610–4. https://doi.org/10.5281/zenodo.1056553.
[29]	Armand P, Lignie A, Beaurain M, Papet P. Flux-grown piezoelectric materials: application to α-quartz analogues. Curr Comput-Aided Drug Des. 2014;4:168–89. https://doi.org/10.3390/cryst4020168.
[30]	Khan R, Gul B, Khan S, Nisar H, Ahmad I. Refractive index of biological tissues: review, measurement techniques, and applications. Photodiagn Photodyn Ther. 2021;33: 102192. https://doi.org/10.1016/j.pdpdt.2021.102192.
[31]	Yu YI, Lazareva EN, Tuchin VV. Refractive index of adipose tissue and lipid droplet measured in wide spectral and temperature ranges. Appl Opt. 2018;57:4839–4848. https://doi.org/10.1364/AO.57.004839.
[32]	Gerrity RG. The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol. 1981;103:181–90.
[33]	Takaku M, et al. An in vitro coculture model of transmigrant monocytes and foam cell formation. Atertio Thromb Vasc Biol. 1999;19:2330–9.
[34]	Li Y, et al. Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol. 2001;7:630–6. https://doi.org/10.3748/wjg.v7.i5.630.
[35]	Cheng JX, Potma EO, Xie SX. Coherent anti-Stokes Raman scattering correlation spectroscopy: probing dynamical processes with chemical selectivity. J Phys Chem A. 2002;106:8561–8. https://doi.org/10.1021/jp025774b.