Thermal Fiber Tapering for the Fabrication of Multifunctional Fiber-based Neural Probes

Abstract

Multimodal neural probes are powerful tools for interrogating neural circuitry in vivo in both clinical and research applications. Current cleanroom fabricated neural probes are delicate, and rely on complex high-cost procedures. Thermal drawing process (TDP) is a method for low-cost scalable fabrication of robust multimodal fiber neural probes. However, connecting such probes is a complex and delicate process due to the small size of the probe sensing elements. This limits the potential of fiber-based neural probes since more complex devices cannot be connected. To address this challenge, I developed a new fabrication process called thermal tapering process (TTP). Instead of using TDP to draw the fiber down to its final size, I first drew thicker fibers called mini-preforms. The mini-preforms are then heated and tapered via TTP, cut in the middle and connectorized, yielding two tapered fiber probes with large backends for ease of connection while retaining small sensing ends for minimal damage during probe insertion. We then leveraged TTP to fabricate the triple modality TDOpE (Tapered, Drug delivery, Optical stimulation, electrophysiology) probe, which cannot be fully connected if fabricated via TTP due to its complexity. We then utilized TDOpE probe's multifunctionality to study the effects of cannabinoid receptor agonist CP-55940 in awake and behaving mice. Fiber photometry is a low-cost method of optically monitoring population level neural activity that complements electrophysiology. However, integrating the two functionalities into one single device has been challenging. Here, I developed and utilized an improved version of TTP called thermal taper-break which improves probe modularity and size profile to develop a chronic fiber probe capable of simultaneous photometry, optogenetics and electrophysiology. In vivo demonstration of the probe's capabilities was conducted via chronic recordings on awake and freely moving mice. Multimodal modulation of neural activity can help further our understanding of neural circuitry. Monitoring of the brain's chemical environment is an important sensing modality frequently performed via microdialysis capable probes. However, such technologies have low temporal resolution. Here, we developed a cost-effective multimodal neural probe capable of sub-second resolution droplet-based microdialysis, electrophysiology and optogenetics using TTP. We also demonstrated real-time Raman sensing detection of biomolecules and in vivo validation of the probe's functions. Current generation neural probes lack modularity after fabrication. A probe whose geometry and functionality can be altered for each individual experiment is essential for neuroscientific studies that require different device modalities at different phases of the experiment. Utilizing TTP, we developed the multifunctional MoRF (Modular, Reconfigurable Fiber) probe, a device whose functionalities can be freely altered, and its sensor geometry reconfigured post-fabrication. It is also the first thermally drawn fiber neural probe to demonstrate simultaneous 32 channel electrophysiology recording. We validated the device's modularity by demonstrating several possible configurations with different functionalities, including optogenetic stimulation, drug delivery, electrical recording, and chemical sensing. MoRF probe's in vivo capabilities are also tested via device implantation and recording in awake and behaving mice. The complex multimodal probes described in this thesis demonstrate that the TTP method can be utilized to overcome the challenges of TDP, allowing researchers to design and fabricate a new generation of fiber-based neural devices with denser sensor arrays, improved multifunctionality and enhanced modularity.