| Popis: |
From research to clinical neuroscience, high-resolution and minimally invasive neural interfaces are needed to study and treat brain function and dysfunction. Recently, optical techniques such as optogenetics and functional fluorescent imaging have enabled unprecedented throughput and specificity for interrogating neural circuits. However, the scattering and absorption of light in the brain tissue limits the resolution and depth of penetration of light-based methods. Therefore, implantable devices are used to deliver or collect light deep in the tissue with high spatial resolution. Currently, implantable optics are typically composed of rigid materials including silicon or silicon dioxide. These stiff materials have a significant mechanical mismatch with the soft brain tissue, triggering tissue damage and scar tissue formation over time. To alleviate these issues and enable minimally invasive chronic optical implants, they must be compact and flexible. This thesis introduces two novel microfabricated device architectures to address this outstanding need in the field. The first, Parylene photonics, uses flexible biocompatible materials – Parylene C and polydimethylsiloxane (PDMS) – to form a novel photonic waveguide platform to passively guide light into or out of the tissue. The second, GaN-on-Parylene micro-light-emitting diodes (µLEDs), uses integrated light sources to generate light directly in the tissue. Due to the flexible polymer material composition and micrometer-scale structures implemented using a novel microfabrication process in both architectures, the devices can be made compact and flexible. In addition, recording electrodes for electrophysiology readout are monolithically integrated to allow for full read-write optogenetic stimulation and electrical recording capabilities in a flexible material platform. I will discuss the design, simulation, fabrication, characterization, and biological demonstration of these novel devices. I present a complete course of work from concept to application for two separate solutions to an outstanding need in the neuroscience toolset, as well as a discussion of their respective benefits and tradeoffs. In the first platform, Parylene photonics, I demonstrate through a simulation study that the refractive index contrast between Parylene C and PDMS is sufficient to confine and guide optical modes in compact, high-density waveguide routing. I developed a novel fabrication process to realize low-loss (< 5 dB/cm @ 633 nm) photonic waveguides in a new Parylene C material platform with integrated 45-degree micromirrors for broadband out-of-plane input coupling and light delivery capabilities. The Parylene photonic waveguides were packaged and implanted in opsin-expressing mice to demonstrate optogenetic stimulation of neurons. In the second platform, GaN-on-Parylene µLEDs, I demonstrate a novel microfabrication process to create arrays of GaN µLEDs directly embedded in a Parylene C substrate. The proof-of-concept devices contain arrays of up to 32 GaN µLEDs as small as 22 µm x 22 µm. I developed a thermal and optical model of the system in the tissue via simulation studies to determine thermally safe stimulation paradigms using the novel device architecture. Finally, I use the GaN-on-Parylene µLEDs to perform optogenetic stimulation of opsin-expressing brain slices. In addition, the potentials of these platforms for realizing surface devices for electrocorticography (ECoG) recording and imaging will be discussed. |
