MRI: Development of an Active/Adaptive Scanning Laser Microscope

蒙大拿州立大学被授予开发一种扫描激光显微镜，该显微镜结合了快速主动聚焦控制和自适应像差校正，可以在厚厚的活组织或完整的动物中提供高质量的三维显微图像。完整组织的光学显微镜，加上可以根据特定细胞类型和结构进行遗传编码的荧光标记的爆炸性进展，是生物发育和功能基础研究的极其强大的工具。然而，为了实现这种方法的潜力，有必要提高深部组织成像技术的空间和时间分辨率。完整组织的显微镜存在分辨率低、对比度低和效率低的问题，这是由于样品中的光束焦点恶化所致。这种新型显微镜使用了两种可变形镜来控制焦深和产生的图像质量。除了新的显微镜光学，该项目还开发了必要的控制算法和用户界面，以创建一种仪器，该仪器将致力于发育生物学和神经科学的研究和研究培训。拟议中的仪器将促进解决神经系统如何发展和功能的基本问题的研究。虽然该项目是专门建造扫描激光显微镜，但潜在的技术可以在未来为广域显微镜带来许多相同的好处。有源光学和自适应光学还有其他潜在的应用，包括小型相机和内窥镜，以及能够在不移动透镜的情况下进行高速聚焦和像差校正的光学数据存储读/写头。因此，这项技术具有广泛的相关性。除了它的科学影响，该项目还包括研究和教育的整合，培训两名工程学研究生，并为几名工程和生物科学本科生提供跨学科的研究经验。将开发一个新的课程模块，以主动/自适应显微镜为平台教授先进的生物光子学方法。

An award is made to Montana State University to develop a scanning laser microscope that incorporates fast active focus control and adaptive aberration correction to provide high-quality three-dimensional microscopic images within thick living tissue or intact animals. Optical microscopy of intact tissues, coupled with the explosive advance of fluorescent markers that can be genetically encoded to specific cell types and structures, is an incredibly powerful tool for fundamental research into biological development and function. To realize the potential of this approach, however, it is necessary to improve the spatial and temporal resolution of deep-tissue imaging techniques. Microscopy of intact tissue suffers from low resolution, low contrast and poor efficiency due to deterioration of the beam focus deep in the specimen. The new microscope uses two types of deformable mirrors to control both the depth of focus and the quality of the images produced. In addition to the new microscope optics, the project also develops the necessary control algorithms and user interface to create an instrument that will be devoted to both research and research training in developmental biology and neuroscience. The proposed instrument will facilitate research that is addressing fundamental questions about how nervous systems develop and function. While the project is specifically constructing a scanning laser microscope, the underlying technology can bring many of the same benefits to wide-field microscopes in the future. Active and adaptive optics have other potential applications, including small-format cameras and endoscopes and optical data storage read/write heads capable of high-speed focus and aberration correction with no moving lenses. The technology is therefore broadly relevant. In addition to its scientific impact the project embraces integration of research and education, training two engineering graduate students and providing cross-disciplinary research experience for several undergraduate engineering and bioscience students. A new course module will be developed that features the active/adaptive microscope as a platform to teach advanced biophotonic methods.