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

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.