基于柔性机构的光学扫描系统与非线性光学内窥显微镜的研究

Many breakthroughs in biology and medicine are driven by the advancement of new diagnostic tools. Meso- and microscale scanning and actuation technologies are the bottlenecks that limit the miniaturization of many high performance optical imaging systems such as a laser scanning two-photon microscope. This is attributed to the (1) limited microactuator performance and (2) limited range/stroke of silicon-based flexure mechanisms. This project will study the fundamental phenomena and physics of several microactuation mechanisms and develop a multi-variable parametric model. Based on the model, we will develop new meso-/microscale actuators and scanners that have 10 times the performance than the state-of-the-art devices. We will also develop new flexure mechanism and actuation technology based on metallic glasses that fundamentally overcome the elastic deformation limit of silicon-based devices. By integrating the aforementioned research results, we will miniaturize a macroscale two-photon microscope into endoscope format that significantly increases the performance of existing endoscope systems. Our new two-photon endomicroscope can generate real-time optical cross-section images from 0 - 500 microns in depth with subcellular resolution. Upon completion, the endomicroscope will be used to perform in vivo biological studies; for example, to track cells in internal organs including the spleen, the mesenteric lymph node, and the kidney. These experiments will validate the importance of new instrumentations for biological and medicinal research.

生物医学领域的许多突破都是以研究工具和诊疗工具的进步为前提，而中微尺度的驱动与扫描技术正是限制许多如双光子显微镜等高分辨率光学系统小型化的瓶颈。其关键点在于当前微驱动器的性能限制以及硅基挠曲器件的行程限制。为此本项目将深入研究微驱动技术的物理机制，建立更加准确与多参数化的物理模型。在此基础之上，将研发十倍于当前器件性能的中微尺度的精密驱动与扫描器件。同时，将研究以金属玻璃为材料制成的柔性机构的动力学及驱动原理，从根本物理机制上突破挠曲器件的行程限制。通过整合上述研究结果可将双光子显微镜小型化到内窥镜尺寸，大幅提升非线性光学内窥显微系统的性能，使其可以在不同深度上（0-500微米）实时获得亚细胞分辨率的光学切片图像。最后将尝试把该种内窥显微镜应用于活体生物的研究，例如在动物脾脏或肾脏内观察细胞等，以此验证该技术在生物医学研究领域的重要作用。

本项目“基于柔性机构的光学扫描系统与非线性光学内窥显微镜的研究” 在基金委的自助下，从2014年起至今，完成了设定的目标，取得了一系列预期的科研成果。通过开展本项目，获得了(1)可用与活体成像过程的新一代中微尺度的精密驱动与扫描器件的物理模型与设计依据；(2)可用于制造激光扫描机构的大行程挠曲器件的参数模型与方法；(3)高分辨率无创内窥扫描成像系统及设计方法。这些科学探索与发明可以显著地促进微驱动器、挠曲机制以及小尺寸扫描与定位技术的进步，为研发实用的新一代小尺寸扫描与定位器件打下了基础。通过填补实用的小尺寸驱动器与高度挠性轴承技术的缺失，提高了小尺寸驱动与定位器件的性能指标，进而将直接促进内窥显微成像、微米尺度光学校准与定位以及基于探针的微纳加工等领域的进步。

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