Date of Award

Spring 1-1-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Jae-Woong Jeong

Second Advisor

Frank Barnes

Third Advisor

Jianliang Xiao

Fourth Advisor

Hanh-Phuc Le

Fifth Advisor

Kimberly Newman

Abstract

Chronic in-vivo studies through multimodal modulation of neurons in the deep brain can render pivotal insights not only in identifying their roles for a specific activity, but also to decipher their contribution in various neurodegenerative diseases. To prevent askew effects, probes were implanted to directly reach the target sites and the spatiotemporal resolution was further improved by targeting key neural circuits using optogenetics and pharmacology. Multimodal optofluidic probes allow integrated access to the target region without the need for multiple surgeries thus reducing tissue damage as well as simplifying combinatorial stimulations. Conventional tools have relied on rigid metal cannulas and silica optical fibers, but they cause adverse tissue inflammation due to their large probe sizes, rigid materials and associated tethers which severely limit their chronic integration. However, minimally invasive, mechanically compliant and untethered probes are shown to significantly limit tissue scarring in freely moving animals as shown in recent advances in soft optofluidic probes controlled by wireless head mounts, however, they didn’t last long primarily due to exhaustion of the drugs and power. Moreover, they were limited to the brain due to their bulky head mounts with limited range, directionality, and selectivity. Here we introduce two wireless optofluidic (wOF) neural devices each solving unique challenges faced by previous state-of-the-art devices and commercial pumps. Firstly, is the Lego wOF device which enables: 1) uninterrupted drug supply using replaceable “Lego” drug cartridges and 2) an easy-to-use smartphone app that allows long wireless range (~100m), isotropic wireless access, no Line of Sight (LOS) handicap, Over The Air (OTA) updates, high target specificity and scalable closed loop systems within a large group as well as intuitive control through an easy to use app on any commercial handheld smartphone. Second is the fully implantable wOF device which enables: 1) both central and peripheral stimulation in any space critical location inside the body (92% smaller and 88% lighter than previous systems), and 2) battery-free operation using a soft, stretchable energy harvester that can conformally adhere to any curvilinear surface inside the body. Successful in-vivo studies in mice demonstrate their innate capability for programmable and chronic wireless pharmacology and optogenetics.

Available for download on Wednesday, November 13, 2019

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