1 山西医科大学第一医院核医学科, 分子影像精准诊疗协同创新中心山西 太原 030001
2 山西大学量子光学与光量子器件国家重点实验室, 激光光谱研究所山西 太原 030006
生命科学的发展一直伴随着显微技术的创新。基于超快光学的单分子相干调制显微成像技术在量子力学的理论基础上, 通过结合超快光学和显微技术使观测生物的微观量子现象成为可能。这篇综述首先介绍了该技术利用飞秒激光脉冲对实现了单分子量子相干态的操控, 并通过调制解调技术获得单分子周围相干信息的基本原理。然后分别介绍了其在生物方面的两个应用: (1)通过降低生物自荧光和背景噪声,实现了生物成像对比度两个数量级的提高; (2)通过提取相干可视度V获得了单分子周围微观的量子信息, 为生物体微环境的观察提供了有效手段。最后文章对基于单分子相干调制显微成像在癌症研究方面做了展望, 该方法将为癌症的早期诊断和预后评估提供新的途径。
显微成像 单分子相干调制 超快光学 成像对比度 相干可视化 癌症检测 microscopy single-molecule coherent modulation ultrafast optics imaging contrast coherent visualization early cancer diagnosis
中国科学院苏州生物医学工程技术研究所医用检验技术研究室，江苏 苏州 215163
拉曼光谱技术作为一种非接触性光子光谱检测技术，可以直接无损地检测细胞内的分子组成和结构变化，实现对癌变细胞的快速精准判别。恶性肿瘤是导致人类死亡的第一大疾病，因此肿瘤早期检测成为近年来医学界的重要研究方向。介绍了几种拉曼检测技术的原理，对拉曼检测技术用于肿瘤组织实体、组织病理切片、患者血清及肿瘤单细胞的检测分析进行综述，并对此技术在乳腺肿瘤、消化系统肿瘤、皮肤肿瘤及脑胶质瘤方向的研究进展展开讨论。与正常细胞相比，肿瘤细胞中生物大分子的成分和含量都会发生一定的变化，拉曼光谱技术可快速精准地检测此类变化，因此对实现肿瘤的早期检测有重要的意义。
激光与光电子学进展
2022, 59(6): 0617016
医学光电科学与技术教育部重点实验室, 福建省光子技术重点实验室, 福建师范大学, 福州 350007
外泌体是一种含有蛋白质、核酸和脂质等物质的小囊泡, 与细胞间通信和肿瘤微环境的调节有关, 因而成为一种新兴的无创早期癌症诊断标志物。目前用于外泌体分析的技术较复杂, 并且耗时久、成本高。近年来, 表面增强拉曼光谱(SERS)技术由于其灵敏度高、样品制备简单、快速无损等优点, 在生物医学领域表现出了巨大的应用潜力。本文首先简要介绍了外泌体以及目前主要检测方法的优缺点, 其次, 阐述了SERS的基本原理及其在外泌体检测中的优势, 重点介绍了非标记和标记SERS在外泌体检测中的应用进展。系列研究表明, 基于SERS的外泌体检测技术有望成为一种无损、便捷、准确的临床诊断新方法。
表面增强拉曼光谱 外泌体 非标记 标记 早期癌症诊断 surface-enhanced Raman spectroscopy exosomes non-marker marker early cancer diagnosis
Author Affiliations
Abstract
1 City University of Hong Kong, Department of Biomedical Engineering, Kowloon, Hong Kong SAR, China
2 City University of Hong Kong, Shenzhen Research Institute, Shenzhen, China
Optical-resolution photoacoustic microscopy (OR-PAM) has been developed for anatomical, functional, and molecular imaging but usually requires multiple scanning for different contrasts. We present five-wavelength OR-PAM for simultaneous imaging of hemoglobin concentration, oxygen saturation, blood flow speed, and lymphatic vessels in single raster scanning. We develop a five-wavelength pulsed laser via stimulated Raman scattering. The five pulsed wavelengths, i.e., 532, 545, 558, 570, and 620 / 640 nm, are temporally separated by several hundreds of nanoseconds via different optical delays in fiber. Five photoacoustic images at these wavelengths are simultaneously acquired in a single scanning. The 532- and 620 / 640-nm wavelengths are used to image the blood vessels and dye-labeled lymphatic vessels. The blood flow speed is measured by a dual-pulse method. The oxygen saturation is calculated and compensated for by the Grüneisen-relaxation effect. In vivo imaging of hemoglobin concentration, oxygen saturation, blood flow speed, and lymphatic vessels is demonstrated in preclinical applications of cancer detection, lymphatic clearance monitoring, and functional brain imaging.
optical-resolution photoacoustic microscopy stimulated Raman scattering single-shot multi-contrast microscopy early cancer detection Advanced Photonics
2021, 3(1): 016002
福建师范大学光电与信息工程学院医学光电科学与技术教育部重点实验室暨福建省光子技术重点实验室, 福建 福州 350007
光声成像技术通过检测光声效应中的超声信号,克服了光在生物组织体传输过程中的强散射作用,突破了传统光学成像的成像深度浅以及声学成像的对比度低的局限,在早期癌症检测中具有广泛的应用前景,有望成为肿瘤的诊断、定位、分期和治疗的有效手段。主要阐述了光声成像技术原理及其在早期癌症检测和治疗中的国内外临床应用研究现状,展望了光声成像技术在生物医学的应用潜力,分析了其未来的发展趋势和局限性。
成像系统 光声成像 早期癌症 检测 应用 激光与光电子学进展
2019, 56(7): 070001
1 西北大学光子学与光子技术研究所, 陕西 西安 710069
2 Imaging Unit-Integrative Oncology Department, BC Cancer Agency Research Centre, Vancouver,British Columbia V5Z 1L3, 加拿大
3 Photomedicine Institute, Department of Dermatology and Skin Science, University of British Columbia,Vancouver, British Columbia V5Z 4E8, 加拿大
拉曼光谱分析技术可以在分子水平上研究物质分子结构和生化组成信息，具有快速、准确、无创(或低创)等优点，已成为临床早期癌症检测和组织病理生理分析的重要工具。近年来，激光技术、光纤探测器件和光电检测技术的发展，不仅极大促进了新型拉曼光谱分析仪器与技术的研发，更进一步扩展了其临床应用的广度和深度，彰显出其独特的科学内涵与应用价值。对临床拉曼光谱分析技术的理论基础进行了阐述，归纳总结了临床快速拉曼光谱分析集成系统设计思路。在此基础上，以作者相关研究工作为例，探讨了拉曼光谱分析技术在临床癌症早期检测与病理分析中的应用特点，为推动相关基础研究及技术创新提供有益参考。
医用光学 拉曼光谱 早期癌症诊断 临床检测仪器 皮肤癌 肺癌
Author Affiliations
Abstract
1 Laboratory for Advanced Medical Photonics (LAMP) Cancer Imaging Department British Columbia Cancer Research Centre 675 West 10th Avenue Vancouver, BC, V5Z 1L3, Canada
2 Photomedicine Institute Department of Dermatology and Skin Science University of British Columbia and Vancouver Coastal Health Research Institute 835 West 10th Avenue Vancouver, BC, V5Z 4E8, Canada
Raman spectroscopy is a noninvasive, nondestructive analytical method capable of determining the biochemical constituents based on molecular vibrations. It does not require sample preparation or pretreatment. However, the use of Raman spectroscopy for in vivo clinical applications will depend on the feasibility of measuring Raman spectra in a relatively short time period (a few seconds). In this work, a fast dispersive-type nearinfrared (NIR) Raman spectroscopy system and a skin Raman probe were developed to facilitate real-time, noninvasive, in vivo human skin measurements. Spectrograph image aberration was corrected by a parabolic-line fiber array, permitting complete CCD vertical binning, thereby yielding a 16-fold improvement in signal-to-noise ratio. Good quality in vivo skin NIR Raman spectra free of interference from fiber fluorescence and silica Raman scattering can be acquired within one second, which greatly facilitates practical noninvasive tissue characterization and clinical diagnosis. Currently, we are conducting a large clinical study of various skin diseases in order to develop Raman spectroscopy into a useful tool for non-invasive skin cancer detection. Intermediate data analysis results are presented. Recently, we have also successfully developed a technically more challenging endoscopic Laser-Raman probe for early lung cancer detection. Preliminary in vivo results from endoscopic lung Raman measurements are discussed.
Rapid Raman system in vivo skin Raman in vivo lung Raman endoscopic Raman probe early cancer detection Journal of Innovative Optical Health Sciences
2008, 1(1): 95–106
