I-Corps: Translation potential of a depth-resolved magnetic resonance-compatible waveguide for light stimulation in optogenetics

Award ID: 2627410

This I-Corps project is based on the development of an optical waveguide designed for neuroscience and biomedical research. Selectively and precisely stimulating different cortical layers of the brain with light stimulation has been a core technical challenge in optogenetic neuronal studies. The surface illumination is limited to less than 500 m light penetration depth. Implanted optical fiber delivery is currently the most common method, however, it usually excites multiple layers, causing cross-layer crosstalk that complicates interpretation of the results. Directly implanted micro light-emitting diode (LED) arrays also have significant heat generation and are not compatible with Magnetic Resonance Imaging (MRI) scanning, which is an important brain activity monitoring method for optogenetic studies. This device has a body less than 500 micrometers in diameter, which allows insertion similar to commonly used optical fibers, and incorporates six total internal reflection mirrors that align with specific cortical layers. The ability to deliver finely targeted light to individual cortical layers could expand research applications ranging from fundamental studies of sensory and cognitive processing to the development of clinical interventions for conditions such as Parkinsons disease and epilepsy. This I-Corps project utilizes experiential learning coupled with first-hand investigation of the industry ecosystem to assess the translation potential of an optical waveguide designed for neuroscience and biomedical research. This technology represents the first fully optical, magnetic resonance compatible, cortical layer-specific stimulation method for neuroscience. The waveguide has a body less than 500 um, making it easily insertable like the commonly used fiber-based method. In addition, the waveguide consists of six total internal reflection (TIR) mirrors that have equivalent spacing to the targeted six cortical layers. Once inserted, the laser light with designed beam geometry can be "reflected" to the desired layer, with a diverged beam size less than 150 um after 1,000 um propagation along the cortical layer. Also, the waveguide is made of biocompatible materials, can selectively and precisely deliver light to each of the six cortical layers, and has minimal light divergence during light delivery, resulting in precise excitation of the neurons within the selected layer. This technology addresses persistent challenges in optogenetics and may benefit research laboratories working in optogenetics and precision neural stimulation. In the future, this technology may be used in biophotonic biomedical applications for sensory restoration and photodynamic therapy. 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.

NSF Program Director: Ruth Shuman