SBIR Phase I: Integrated Coaxial Electron and Light Microscope for Multimodal Imaging

这个小型企业创新研究(SBIR)第一阶段项目旨在开发一种低成本的组合光学和电子显微镜，可以同时观察同一区域。这样的工具将有益于从多种模式收集信息以理解样本行为的任何应用，例如在生命科学中。目前，通常在不同的实验室使用两台不同的仪器才能实现这一点，需要非常小心地跟踪仪器之间的信息区域。显微镜市场估计价值94亿美元，其中39亿美元包括电子显微镜，30亿美元用于光学显微镜。该项目提出了一种简单、易用的解决方案，将这两个系统结合为一个系统，为显微镜工作者提供了显著的生产力飞跃，并推动了生命科学的发现。该项目的智能优点是基于一种独特而简单的体系结构，该体系结构降低了电子显微镜的成本和复杂性，同时还允许通过两种模式对样品进行同轴成像。在生命科学中，一种日益流行的方法是将高分辨率结构信息(上下文)与关键标记蛋白质的超分辨率荧光图像相结合，以获得对组织功能的了解。用户不需要担心位置跟踪和对准。此外，该体系结构很好地利用了一种新的光学电荷控制方法，以减少样品上的电荷积累，这是电子显微镜常见的问题。用于成像的相同光路允许通过电荷控制光束对样品进行共照明。在提交提案之前，团队完成了详细的粒子光学建模和系统设计优化。这个第一阶段的项目将完成显微镜的机械设计，建立原型，并使用标准电子成像计量靶验证粒子光学模型和由此产生的成像性能。其次，该项目将使用原型来成像一系列充电样本，以测试充电补偿方案。结果图像将与传统桌面扫描电子显微镜获得的图像进行比较，以了解电荷控制的有效性和局限性。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This Small Business Innovation Research (SBIR) Phase I project aims to develop a low-cost combined light and electron microscope having simultaneous view of the same area. Such a tool will benefit any application in which information is gathered from multiple modes to understand the sample behavior, such as in the life sciences. Currently, this is accomplished only with two separate instruments often in different laboratories with great care needed to track the region of information between instruments. The microscopy market is an estimated $9.4 billion, $3.9 billion of which comprises electron microscopes and $3.0 billion for light microscopy. This project advances a simple, easy-to-use solution combining the two systems into one, offering significant leaps in productivity for microscopists and advancing discoveries in the life sciences. The intellectual merit of this project is based on a unique and simple architecture that reduces cost and complexity of the electron microscope while also allowing for coaxial imaging of the sample by the two modalities. In the life sciences, an increasingly popular method is to combine high resolution structural information (context) with super-resolution fluorescence images of key marked proteins to obtain functional understanding of the tissue. The user does not need to worry about position tracking and alignment. Furthermore, the architecture lends itself well to a new optical charge control method for mitigating charge build-up on the sample, a problem common to electron microscopy. The same optical path used for imaging allows co-illumination of the sample by the charge control beam. Ahead of submission of the proposal, the team completed detailed particles optics modeling and system design optimization. This Phase I project will complete the mechanical design of the microscope, build the prototype, and validate the particle optic modeling and resulting imaging performance using standard electron imaging metrology targets. Second, the project will then use the prototype to image a range of charging samples to test the charge compensation scheme. Resulting images will be compared to that obtained from traditional tabletop scanning electron microscopes to understand the effectiveness and limitations of the charge control.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.