基于扫描近场光学显微镜的超高分辨率光声成像技术研究

In the past ten years, PhotoAcoustic Imaging (PAI) technology for medical diagnosis has been developed quickly. The resolution has been elevated to the micrometer scale which approaches the diffraction limit of light. This technology has been successfully adapted to high-resolution structural and functional imaging of biological samples in vivo, from organs to cells. Major preclinical applications include studies on angiogenesis, microcirculations, tumor microenvironments, drug responses, brain functions, biomarkers, and gene activities. In this project, we propose a Super-Resolution PhotoAcoustic Microscopy (SR-PAM) technique based on Scanning Near-field Optical Microscopy (SNOM). To realize this revolutionary technique, research will be conducted through both theoretical analyses and well planned experiments. Once success, the resolution can reach nanometer scale for the first time, breaking the Rayleigh diffraction limit of light and being controlled only by the size of the light beam through the SNOM tip. SR-PAM can realize the studies on organelles, motion of cells, and cell interaction with biological environments in vivo, all on molecular level. This research holds promise to lead to breakthroughs in not only biomedical imaging but also nondestructive evaluation of nanomaterials and nanodevices.

近十年来，用于医学诊断的光声成像技术研究发展很快，分辨率已提高到微米量级，接近光波长衍射极限，实现了从组织层面大幅跨越到细胞层面的高分辨率的结构和功能研究，在血管新生、微循环、肿瘤微环境、药物反应、脑功能、生物标记和基因活性等的诊断和检测方面有独特优势和极大的应用前景。本项目拟将光声成像技术和近场成像技术- - 扫描近场光学显微镜（SNOM）结合，突破瑞利衍射极限的限制，实现纳米尺度上超高分辨率光声成像。此项技术一旦成功，医学光声成像技术将成为一种在分子层面上研究活体细胞成份、运动、以及细胞和环境相互作用的新型显微技术，这对生物医学成像，或是纳米材料/器件的无损评估，都将带来革命性的突破。

本项目将光声成像技术和近场成像技术- - 近场扫描光学显微镜（NSOM）结合，对NSOM系统进行了改装，将激光源改装为纳秒脉冲激光源，样品台改装为中心频率为45 MHz的超声传感平台，对触发信号进行匹配，实现了近场扫描光声显微镜（NSPAM）。在光源为532nm的绿光辐照下，获得的光声图像突破了瑞利衍射极限的限制，分辨率达到35nm，实现了纳米尺度上超高分辨率光声成像，对纳米金属-半导体器件进行了无损评估。NSPAM可实现在分子层面上研究活体细胞的成份、运动、以及细胞和环境相互作用机制，这将为生物医学成像技术带来革命性的突破。