Fiber-DeliveredProgrammableSupercontinuumLaserAdaptivetoEvolvingNeurophotonicResearch

SUMMARY Neurophotonics, including the prominent example of optogenetics, has been the driving force for brain research and one focal area of the NIH BRAIN Initiative established in 2013. In contrast to the genetic and biophotonic advancements that have transformed this field, the progress in laser source technology underlying these advancements has lagged behind, resulting in three technical barriers that limit the next level of scientific achievement in brain and behavioral sciences: (1) neuroscientists and biophotonic scientists have been limited by readily available commercial lasers that may not be the best solutions for their intended applications, due largely to the lack of full tunability in parameters such as wavelength, power, and temporal profile; (2) the user- unfriendly operation of tunable customer or commercial lasers has hindered the extension of laser source technology beyond non-laser experts and dedicated optical laboratories, and (3) the lack of adaption of installed lasers with free-space beam delivery often render them obsolete when new neuroscience needs and applications emerge. A fiber-deliverable programmable supercontinuum laser, based on systematic preliminary work in an academic laboratory, has potential to simultaneously overcome the three technical barriers. The prototype of this laser has shown promise to be applicable to general neuroscience, including diverse species (small animals, rodents, and humans), states (in vitro/ex vivo, head-fixed, and freely behaving), settings (optical laboratory, animal facility, pathology department, and operating room), operators (laser experts, imaging neuroscientists, veterinarians, pathologists, and neurosurgeons), and goals (basic study, therapeutics development, drug discovery, precision pathology, intraoperative assessment, and laser-assisted surgeries). It is thus desirable to seek further Randamp;D opportunity in a small business environment, in order to allow wide access to this laser by the neuroscience community not trained extensively in laser source engineering. In this project, the Randamp;D effort will first aim to overcome the remaining technical obstacles that hinder the seamless integration of coherent fiber supercontinuum generation and programmable pulse shaping, two photonic technologies dispensable for laser source engineering per se but indispensable for the laser source engineering that targets neuroscience. Subsequently, this laser will be tested in two prototypical systems broadly representative of neurophotonic applications with and without neural intervention. The construction of a more reliable prototype of this laser and the demonstration of its feasibility in the two prototypical neurophotonic systems will enable smooth transition of this Randamp;D effort (SBIR Phase I) to Phase II stage. The whole project may ultimately facilitate wide access to cutting-edge ultrafast laser technology by the broad neuroscience community, in consistency with one goal of the NIH BRAIN Initiative to translate innovative technologies for brain or behavioral research from academia to the marketplace.NARRATIVE Optical source engineering and cellular-resolution brain research have been two isolated specialties involving rather different communities. The lack of collaboration between laser engineers and neuroscientists or their colleagues of biophotonic scientists has hindered the emergence of a versatile and user-friendly laser for neurophotonics. We intend to initiate this collaboration in a multidisciplinary industrial-academic setting to develop a fundamentally new laser platform, in order to expand the brain research from dedicated optical laboratories to animal facilities and human hospitals, from neuroscientists to brain pathologists and surgeons, and from basic structural-functional interrogation to drug discovery and therapeutics development, with increased research capabilities and improved adaption to evolving research needs over alternative lasers.