In this Small Business Innovation Research program, we will develop an optical imaging system that uses diamond nanosensors for high-speed parallel recording of neural activity in brain tissue in in vitro and in vivo animal models. The study of neural circuitry is one of the primary drivers in the development of effective treatments and extends our understanding of neurological disorders such as mental illnesses, Alzheimer's disease, Parkinson's disease, and epilepsy. Mental disorders affect one out of every four Americans and cost the US economy over $100 billion a year, with depression being the leading cause of disability. Although neuroscientists have intensively investigated neural circuits and their relation to behavior for decades, current tools hinder progress in this technically challenging field. Capturing the activity of thousands and even millions of cells in real time over a wide field of view (tens to hundreds of micrometers) while resolving features below the diffraction limit is a multi-scale technological barrier that impedes scientific progress. Here, we propose a new method that applies tools from quantum physics, materials science, and engineering to neuroscience research. Our optical detection technology is based on the exceptional sensing capabilities of negatively charged nitrogen-vacancy (NV) color centers in diamond. The NV center represents one of the most sensitive magnetic and electric field probes at sub-100-nm distances at room temperature, making it an ideal candidate for probing action potentials. In addition to its remarkable sensing capabilities, NV fluorescence is extremely bright and photostable (>106 photons/second recorded for months on the same NV center). Moreover, the fluorescence can be deterministically modulated through microwave manipulation of its spin-triplet ground state, allowing for a new kind of super-resolution imaging technique with low excitation power. The combination of bright, stable optical probes with field sensing capabilities that permit localization down to tens of nanometers may enable breakthroughs in neural circuitry research. In Phase I of this program, we will conduct a feasibility study of core aspects that underline our system:  scalable fabrication of diamond nanosensors for neural activity detection; characterization of the sensitivity of nanosensors in an aqueous environment;and  super-resolution imaging of neurons using diamond probes. After successful completion of Phase I, we will construct a working prototype of the system in Phase II, that can be fully integrated with existing tools.
Research on neural circuitry is one of the primary drivers in the development of effective treatments and extends our understanding of neurological disorders such as mental disabilities, Alzheimer's disease, Parkinson's disease, and epilepsy. Mental disorders affect one out of every four Americans and cost the US economy over $100 billion a year, with depression being the leading cause of disability. Our program will put a new tool in the hands of neuroscientists aiming to unravel the complexities of neural networks and reverse engineer their circuits, which will accelerate the pace of discovery and lead to more effective treatments for neurological disorders.