高速超分辨宽带相干拉曼光梳光谱及成像

Broadband coherent Raman spectro-imaging with high spatial resolution is of great importance for the development of basic disciplines such as molecular physics, chemistry and biology. Meanwhile, it provides an important optical means for biological imaging, medical diagnosis and chemical molecular detection. However, the existing hyperspectral imaging system is time-consuming with low sensitivity and very limited spatial resolution due to the diffraction limit of a microscope. On the other hand, super-resolution imaging techniques such as stimulated emission depletion (STED), near-field optical random mapping (NORM) microscopy, near-field scanning optical microscope (NSOM), and so on, fail to provide molecular fingerprint spectral information, and surfer from the use of biomarkers or/and nano metal detection probes which severely limit their scope of application. Aiming at the above problems, our proposal first intends to develop high-brightness coherent femtosecond optical frequency combs as new light sources for coherent Raman spectroscopy. Based on our previous results and solid research backgrounds on laser combs and high-precision spectroscopy and microscopy, we will develop a comb-based coherent Raman spectral imaging technique, combining the broadband Raman spectra with spatial information and offering a one-time, scanning-free 3D color microscopic approach for rapid biological and chemical imaging. We then will develop a high-sensitivity frequency comb spectroscopic technique for ultrafast molecular fingerprinting by using nanoporous gold films for enhanced coherent Raman microscopy. Finally, we will develop a multi-comb stimulated vibration depletion microscopic technique, which may break the fundamental optical diffraction limit for imaging without molecule labeling or plasmonic tips. Our proposed techniques will open a new avenue for exploring new physical mechanisms of molecules in a nanoscopic view.

空间超分辨宽带拉曼光谱成像技术对分子物理学、化学、生物学等基础学科的发展至关重要，是生物微观成像、医学诊断、化学分子检测的重要光学手段。但是，现行的光谱成像系统存在着耗时、灵敏度低和空间分辨率有限的问题；而超分辨成像技术普遍存在着分子指纹光谱信息缺失的问题，并且荧光标记法或者纳米金属探针的接触式探测方式严重限制了其应用范围。针对上述问题，项目拟以发展新型高亮度相干飞秒光频梳光源为切入点，在团队已有的光梳光谱成像技术基础上，拟发展调频光梳相干拉曼光谱成像新方法，解决“图谱合一”的成像难题，实现一次性、无扫描快速成谱的彩色三维成像；拟发展单分子/少分子光梳动态光谱技术，攻克超灵敏分子光谱标识技术难题；拟发展多光梳受激损耗探测显微拉曼光谱成像新技术，实现突破光学衍射极限的无标记、非接触式分子指纹图谱成像，重点解决超分辨光学成像对标记物和探针的依赖问题；为探索分子空间尺度的新物理机制提供新途径。

高分辨超宽带拉曼光谱成像技术对分子物理学、化学、生物学等基础学科的发展至关重要，是生物微观成像、医学诊断、化学分子检测的重要光学手段。但是，现行的光谱成像系统存在着耗时、灵敏度低和空间分辨率有限的问题；而超分辨成像技术普遍存在着分子指纹光谱信息缺失的问题，并且荧光标记法或者纳米金属探针的接触式探测方式严重限制了其应用范围。针对上述问题，项目开展了研究，并在光梳光源与相干拉曼光谱测量与成像研究方面取得成果。项目探究了光纤锁模激光动力学过程，揭示了高重频脉冲产生机理；研制研制成高集成度、重频任意可调的电光调制光梳源。发展出调频双光梳相干拉曼光谱测量新技术，攻克拉曼光谱成谱速率低的问题，实现快速、高分辨相干拉曼光谱显微成像，单次成谱时间仅1us，光谱像素更新速率最高可达1MHz，为目前国际上最高水平；同时，提出基于多光梳的超分辨相干拉曼光谱成像方案；发展出单光子水平的超灵敏双光梳成像方法，通过将双光梳编码成像方式与单光子单点探测技术相融合，解决了成像噪声与灵敏度问题，实现了高分辨、低光子数的光学成像；发展出基于飞秒光场诱导荧光的高光谱成像技术，缓解了高光谱成像技术存在的空间分辨率与成谱分辨率难以兼得的困境，实现2500色彩，0.1nm谱分辨率的三维荧光成像。