This PFI: AIR Research Alliance project focuses on building a sustainable innovation ecosystem in biophotonics, on educating the next generation of entrepreneurs and on accelerating the translation and transfer of key biomedical technologies developed by an NSF Science and Technology Center (STC), the Center for Biophotonics Science and Technology (CBST). The technologies proposed for commercialization in collaboration with our partners will fill technology gaps in the following areas: 1) super-resolution cellular imaging for biology and medicine, 2) novel non-photobleaching labels for imaging of cell dynamics, 3) monitoring cellular response to cancer drugs, and 4) automated blood pathology for disease detection and monitoring. These technologies have the following market-valued features: 1) outstanding image quality at resolutions that are at least 8 times higher (volume-wise) than the diffraction limit, that provide exemplary performance at lower, and thus more forgiving, illumination intensities when compared to leading optical microscopy technologies; 2) provide the ability to use non-photobleaching SERS (surface enhanced Raman scattering) labels for cellular imaging of cell dynamics, for monitoring unique biomarkers that cannot yet be monitored with other techniques; 3) capability to monitor cellular responses to cancer drugs in almost real-time by using Raman cytometry and in a more efficient manner compared with other experimental strategies; and 4) automated, real-time, point-of-care blood testing systems that provide enormous cost savings when compared to impedance-based, large, skilled labor-intensive and expensive commercially-available blood pathology systems. The Ecosystem for Biophotonics Innovation accomplishes this transfer to the market either by working in collaboration with research partners and transferring technologies to them, or via spinoffs, resulting in creation of new jobs (Entrepreneurial Fellows in academia, scientists collaborators in industry, and scientists in startup companies), commercial products for biology and medicine, with the potential to advance research and help patients while also training entrepreneurial scientists and generating licensing and royalty revenues. The partnerships engaged to transfer the technologies to the market domain include: 1) Applied Precision Inc, a GE Healthcare Company - will commercialize software algorithms for next generation super-resolution microscopes; 2) BD Biosciences - will commercialize novel SERS labels for studying cell dynamics; 3) Keaton Raphael Memorial foundation - will invest financial resources to advance technologies for diagnosis and treatment of pediatric cancers and to launch a startup company to commercialize the most promising technologies; 4) SARTA - will provide links to entrepreneurs in the region and educational opportunities; and 5) Tahoe Institute for Rural Health Research - will commercialize the automatic blood pathology system. The potential economic impact is expected to be realized through: 1) employing highly skilled and productive entrepreneurial fellows, faculty, as well as the scientists at our partnering organizations; 2) employing highly skilled scientists in spinoff companies; 3) licensing of technologies; and 4) through product sales (e.g., next generation super-resolution optical microscopes, labels and assays for cellular imaging, assays for monitoring cellular response to cancer drugs, and automated pathology systems), in the next one-to-five years. All these activities will ultimately contribute to the U.S. competitiveness in the biomedical technology market space through ensuring that cutting-edge technologies are commercialized in the U.S. instead of by scientists and companies from other countries and through providing excellent professional development opportunities to talented entrepreneurial fellows who we expect will have innovative and resourceful careers beyond their tenure with EBI. In the short term, the societal impact includes the movement of advanced technologies closer to commercialization, as well as hands-on training and learning for the next generation of scientists and entrepreneurs regardless of whether entrepreneurial fellows pursue careers in academia or in the private sector. In the long term, the societal impact includes enhancement of scientific discovery enabled by cutting-edge instruments, medical devices, techniques and assays, better understanding of biophysical phenomena, and ultimately improved patient care. EBI will also benefit society by strengthening an infrastructure to promote innovation and to educate would-be entrepreneurs, while also enabling universities to more productively partner with private industry.