3-D optical waveguide arrays for in-vivo optogenetics : development and application

Abstract

A key feature of neural circuits in the mammalian brain is their 3-dimensional geometric complexity. The ability to optically drive or silence sets of neurons distributed throughout complexly shaped brain circuits, in a temporally precise fashion, would enable analysis of how sets of neurons in different parts of the circuit work together to achieve specific neural codes, circuit dynamics, and behaviors. It could also enable new prototype neural control prosthetics capable of entering information into the brain in a high-bandwidth, cell-specific fashion. This dissertation work involves the development, characterization, and initial utilization of a technology capable of delivering patterned light to 3D targets in neural tissue. Silicon oxynitride waveguide fabrication was optimized for integration onto insertable silicon probes. The waveguides have a propagation loss of-0.4 dB/cm. Right-angle corner mirrors were fabricated at the outputs of the waveguides with losses measured to be 1.5 ± 0.4 dB. Silicon MEMS techniques were developed to fabricate both single- and multi-shank probe geometries with integrated waveguides. Methods were developed to assemble the multi-shank probes into a 3D format using discrete monolithic silicon pieces. Three coupling schemes were developed to couple light to both single- and multi-shank probes. For individual probes not assembled in a 3D format, ribbon cables were used. Modular connection schemes were developed based on ribbon cable connector technologies. Input coupling losses were measured to be 3.4 ± 2.2 dB. For probes which were assembled in a 3D format, two coupling methods were developed: projector-based and scanning-mirror-based. The losses associated with the projector-based system are 17.3 ± 1.8 dB. With a 1.5W 473 nm laser source, 100 pW is capable of being delivered from 300 separate waveguides. The losses associated with the scanning-mirrorbased system are 11.9 ± 2.5 dB. With a 1.6 mW 473 nm laser source, 100 pW is capable of being delivered from an individual waveguide. These fabrication, assembly, and coupling methods demonstrate a successful development of a technology capable of delivering patterned light to 3D targets in neural tissue. Initial biological experiments being performed on microbial-opsin expressing mice is presented. 3D patterned light is delivered to targets in the primary somatosensory cortex while electrical activity is recorded from the primary motor cortex.