Optical gearbox enabled high-speed multiphoton microscope

ABSTRACT Neurological disorders affect millions of people each year, many with no cures. Researchers and clinicians are actively seeking a deeper understanding of how the human brain functions to develop new treatments and cures. Optical functional imaging is a tool broadly applied in neuroscience. The advance of genetically encoded functional indicators allows the visualization of neuronal activities with light in the living brain. Currently, laser scanning two-photon fluorescence microscopy (TPM) remains the most widely employed solution for deep imaging in the mammalian brain. Current TPM is too slow to keep up with neuronal signals which are transmitted and processed on the millisecond time scale. Although some high-speed imaging methods exist, their complexity, tradeoff, and cost have prevented adoption and broad utilization by most labs. There is an unmet market need for a simple and easy-to-use high-speed TPM imaging system. Photomatrix, an Indiana-based small business, was formed to commercialize emerging technology from Purdue University (Meng Cui, PI) based on previous NIH-funded research. Photomatrix’s optical gearbox, an add-on unit to existing laser scanning microscopes, can flexibly change the scan rate and field-of-view (FOV) by adjusting the gear ratio. To develop the technology for the commercial neuroscience market, the team will develop an optical gearbox-based TPM with robust performance, compact design, and user-friendly interface. Phase I efforts will focus on demonstrating the feasibility of the technology with the following Aims. 1: Develop a preliminary prototype of a compact optical gearbox for high-speed TPM with a 200 kHz line rate. The gearbox-based TPM must be compact and robust to meet customer needs. The team will construct a compact and solid system of long-term stability with a footprint of less than 2’x3’ and a maximum line scan rate of ~200 kHz for fast purely linear scanning. 2: Integrate gearbox with ultra-large etendue detection for superior imaging depth and quality. Using preliminary data, the team will integrate the gearbox with this ultra-large etendue detection for superior imaging depth and quality to achieve at least a 300% increase in signal strength for deep tissue imaging. 3: Develop the FPGA-based data acquisition system and basic user interface (UI) functions. Photomatrix must develop an integrated Field Programmable Gate Arrays (FGPA) based data acquisition system to fully control the system with a single device. The UI will resemble ScanImage software in functionality and appearance but will offer much-improved imaging speeds. At the end of Phase I, Photomatrix will have a prototype high-speed TPM system with ~200 kHz line rate, demonstrated superior deep tissue imaging performance, and a fully functional UI. Phase II will focus on converting the prototype system into a commercially viable solution with a full software package that can be easily adopted in the field and sold to research labs across the globe. Photomatrix is targeting the adoption of 100 systems in the first three years of commercialization and up to 500 within 10 years with a current market size exceeding $210M.