The aim of this dissertation is to summarize my research on the development of multifunctional multimaterial fibers that are designed and produced for sensing and modulation applications in wearable and biomedical fields. Fiber-shaped devices have gained significant attention due to their potential in human-machine interface applications. These devices can be woven into fabrics to create smart textiles or used as implantable probes for various biomedical purposes. To meet the requirements of human-machine interface, these fiber devices need to be flexible, robust, scalable, and capable of integrating complex structures and multiple functionalities. The thermal drawing technique has emerged as a promising method for fabricating such fiber devices. It allows for the integration of multiple materials and intricate microstructures, thereby expanding the functionality and applications of the devices. However, the range of materials and structures that can be integrated into these fiber devices is still limited, posing a constraint on their potential applications. To address this limitation, the dissertation focuses on expanding the range of materials and structures that can be integrated into multimaterial fiber devices. This involves the development and application of stretchable electrical and optical deformation fiber sensors by incorporating composite thermoplastic elastomers through the thermal drawing process (Chapter 2). Additionally, the dissertation explores the use of the thermal drawing technique to create multifunctional ferromagnetic fiber robots capable of navigation, sensing, and modulation in minimally invasive surgery (Chapter 3). Furthermore, the integration of nano-optoelectrodes and micro robotic chips on the fiber tip using the combination of thermal drawing and lab-on-fiber techniques is investigated (Chapter 4). The dissertation concludes with an overview of the research findings and potential future directions in the field of multifunctional multimaterial fiber devices (Chapter 5). / Doctor of Philosophy / Human-machine interface (HMI) is the technology that enables communication and interaction between humans and machines or computer systems. It plays a vital role in various domains, including consumer electronics, robotics, healthcare, virtual reality, and industrial automation. Fiber-shaped devices have recently emerged as a promising technology for HMI applications due to their flexibility, lightweight nature, and versatile functionality. These devices can be seamlessly integrated into wearable forms, such as clothing or accessories, and even implanted in the body, opening up a wide range of possibilities for HMI. In the past decades, significant progress has been made in developing multifunctional multimaterial fiber devices using the thermal drawing process (TDP). TDP allows for the fabrication of fibers with complex geometries and microstructures by heating and drawing a preform consisting of different materials. However, the current range of materials and structures that can be integrated into these fiber devices is still limited, which hinders their potential applications. This dissertation aims to expand the capabilities of multimaterial fiber devices by exploring new materials and structures that can be incorporated using TDP. The research focuses on three main areas. First, the development and application of stretchable electrical and optical deformation fiber sensors by integrating composite thermoplastic elastomers are explored (Chapter 2). This enables the sensing of various deformations, enhancing the functionality of the fiber devices. Second, the dissertation investigates the creation of multifunctional ferromagnetic fiber robots capable of navigation, sensing, and modulation in minimally invasive surgery (Chapter 3). These robots offer new possibilities for precise and controlled interventions. Lastly, the integration of nano-optoelectrodes and micro robotic chips on the fiber tip using a combination of thermal drawing and lab-on-fiber techniques is explored (Chapter 4). This allows for advanced optical sensing and remote-control capabilities at the fiber tip. Overall, these three aspects of the project broaden the capabilities and functionalities of multifunctional multimaterial fibers, making them highly versatile and suitable for a wide range of applications in wearable technology and biomedicine. These advancements have the potential to revolutionize the field of human-machine interface (HMI) by enabling seamless and intuitive communication, control, and feedback between humans and machines.

The aim of my Ph.D. thesis is to summarize my research on the development of multimateiral multifunctional fibers for bio-related application, mainly in the fields of neural interfacing and bioimpedance sensing. Understanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires the development of improved miniaturized neural interfaces that integrate into brain tissue without altering its properties. Despite the advancement of the existing neural interface technologies such as microwires, silicon-based multielectrode arrays, and electrode arrays with flexible substrates, the physical properties of these devices limit their access to one, small brain region with single implantation. Beyond neural interfacing, extracting molecular information is crucial for understanding many neurological diseases and disorders. The most adapted methods are fast scan cyclic voltammetry and microdialysis. However, both have some limitations such as offline sensing or lack of selectivity. Furthermore, by concentrating optical fields at the nanoscale, plasmonic nanostructures can serve as optical nanoantennas to achieve ultrasensitive bio-/chemical sensing. But due to the limitation of the sensing mechanism, it is hard to perform the plasmonic sensing in live animals. Moreover, the relatively poor electrical performance of the electrode materials that can be utilized in the thermal drawing process limits the function of the fiber in other types of biomedical application, such as deep brain stimulation and electrochemical sensing. For example, the large inherent electrical resistance of the electrode material will significantly interference the electrical impedance result while the main purpose of this kind of study is to explore the frequency-dependent electrical properties of the tested subjects. To overcome above difficulties This thesis introduces broad application of multimaterial multiplexed fibers in biomedical areas. I first describe the development and application of spatially expandable multifunctional fiber-based probes for mapping and modulating brain activities across distant regions in the deep brain (Chapter 2). Secondly, I present the flexible nano-optoelectrodes integrated multifunctional fiber probes that can have hybrid optical-electrical sensing multimodalities, including optical refractive-index sensing, surface-enhanced Raman spectroscopy, and electrophysiological recording (Chapter 3). Thirdly, I demonstrate that hollow multifunctional fibers enable in-line impedimetric sensing of bioink composition and exhibit selectivity for real-time classification of cell type, viability, and state of differentiation during bioprinting (Chapter 4). The same device allows for local delivery of immune checkpoint blockade antibodies and for monitoring of clinical outcomes by tumor impedance measurement over the course of weeks with the photodynamic therapy option to enhance anti-tumor immunity and prolong intratumoral drug retention (Chapter 5). An overview future work has been summarized (Chapter 6). / Doctor of Philosophy / Electrode technology has played an indispensable role in neuroscience community since the first employment of insulated tungsten wire in cat brain in 1950s. The electrophysiological signal acquired from or the electrical current delivered to the brain tissue using the implanted electrode, has permitted us to understand the functional networks in the brain and treat neurological diseases. Over the past decades, significant progress has been made in developing miniaturized electrical neural interfaces. The development of optogenetics involving genetically-modified neurons that express light-sensitive proteins (opsins) has provided a powerful tool for modulating the neuronal activity to be switched on or off using light at a particular wavelength. Leveraging the thermal drawing process (TDP) from optical fiber industry for producing conventional silica fibers, multifunctional fiber-based neural probes have recently been developed, allowing for simultaneous optical stimulation, electrical recording, and drug delivery in vivo. However, the interfacing sites in these fiber-based neural probes have been restricted to a single location (at the fiber tip) so far, making the broad application of these probes unfeasible. Beyond neural interfacing, extracting molecular information is crucial for understanding many neurological diseases and disorders. The most adapted methods are fast scan cyclic voltammetry and microdialysis. However, both have some limitations such as offline sensing or lack of selectivity. Furthermore, by concentrating optical fields at the nanoscale, plasmonic nanostructures can serve as optical nanoantennas to achieve ultrasensitive bio-/chemical sensing. But due to the limitation of the sensing mechanism, it is hard to perform the plasmonic sensing in live animals. To overcome these limitations, we first developed a platform that provides three-dimensional coverage of brain tissue through multifunctional polymer fiber-based neural probes capable of interfacing simultaneously with neurons in multiple sites (Chapter 2). In a later study, we demonstrate that conductive nanoantenna arrays can be integrated with microelectrodes on the tip of multifunctional fiber probes as nano-optoelectrodes to enable optical bio-/chemical spectroscopy as well as to improve electrophysiology recording (Chapter 3). Besides, inspired by a convergence fiber drawing method, we have also managed to incorporate copper wires inside multifunctional fibers with a hollow channel in the center, in favor of high electrical conductivity. This technology developed here holds great promise for electrochemical impedance sensing of the tested media without the interference from the utilized electrodes' high resistance. Hence, by exploiting the functional fibers and the superior electrical performance, the copper-electrode-based fiber has been used for in vitro bioink bioimpedance sensing during 3D printing process (Chapter 4) and in vivo tumor impedance monitoring and drug delivery (Chapter 5). In summary, my research produces unique platforms for fundamental research studies as well as the readily translational application for human subjects. Given the scalable, straightforward, and versatile fabrication method, the multifunctional fibers delivered by our team would pave the way for new engineered tools for broad biomedical community.

Biomedical devices play a crucial role in the healthcare system, enabling more effective treatments, less invasive procedures, and more precise diagnoses. Due to these compelling reasons, development of new biomedical devices and biomaterials have always been in high demand. Exploring and refining fabrication methods are essential to the development of new biomedical devices. Some of the common fabrication methods include microfabrication methods (photolithography and soft lithography), 3D printing (additive manufacturing), laser machining, thermal drawing, and electrospinning. The choice of fabrication methods heavily depends on the materials, geometry, and functionalities of biomedical devices. Currently, the thermal drawing process has proven to be an excellent scalable fabrication platform for neural interface, tissue engineering, tumor/cancer treatment, soft robotics, and smart textiles. This Ph.D. dissertation summarizes my research on the fabrication and validation of thermally drawn multifunctional polymer fiber probes for modern biomedical applications, primarily in the fields of neural interfaces and tumor treatments. Understanding the neural basis of behavior requires monitoring and manipulating combinations of physiological elements and their interactions in behaving animals. Utilizing the thermal drawing process, we developed T-DOpE (Tapered Drug delivery, Optical stimulation, and Electrophysiology) probes and Tetro-DOpE (Tetrode-like Drug delivery, Optical stimulation, and Electrophysiology) probes that can simultaneously record and manipulate neural activity in behaving rodents. Taking advantage of the triple-functionality, we monitored local field potential (LFP) while manipulating cannabinoid receptors (CB1R; microfluidic agonist delivery) and CA1 neuronal activity using optogenetics. Focal infusion of CB1R agonist downregulated theta and sharp wave-ripple oscillations (SPW-Rs). Furthermore, we found that CB1R activation reduces sharp wave-ripples by impairing the innate SPW-R-generating ability of the CA1 circuit. Microscale electroporation devices are mostly restricted to in vitro experiments (i.e., microchannel and microcapillary). We developed a flexible microscale electroporation fiber probe through a thermal drawing process and femtosecond laser micromachining techniques. The novel fiber microprobes enable microscale electroporation and arbitrarily select the cell groups of interest to electroporate. Successful reversible and irreversible microscale electroporation was observed in a 3D collagen scaffold (seeded with U251 human glioma cells) using fluorescent staining. Leveraging the scalable thermal drawing process, we envision a wide distribution of multifunctional polymer fiber probes in research facilities and hospitals. Along with the fiber probes presented in this dissertation, additional insight and future perspective on thermally drawn biomedical devices are discussed. / Doctor of Philosophy / The thermal drawing process is a versatile and scalable platform for fabricating functional fiber technology. The process was formerly adapted from fabrication method for silica optical fibers, widely used in telecommunication (e.g., telephone, internet, cable TV, etc.). To name some functionalities of these fibers, they can move, hear, sense touch, change colors, harvest and store energy, record and manipulate brain activity, and ablate tumors. As imagined, these functionalities are derived from the unique geometry and functional materials embedded along the fiber. Therefore, developing the fiber design tailored to a specific application is a critical step to making a successful fiber product. In this dissertation, I will present my work on biomedical devices fabricated with the thermal drawing process and their application in neuroscience and tumor/cancer treatment. Utilizing the thermal drawing process, we developed neural interfaces that can be implanted into the deep brain and record and simultaneously manipulate the neural activity. These neural interfaces (Chapter 2,3; T-DOpE and Tetro-DOpE probes, respectively) are able to record both local field potentials (LFP; activity of thousands or more neurons) and single action potentials (single on/off signal from individual neurons nearby). By manipulating the gene expression, we can control the activity of neurons with specific light (λ= 470nm; blue light) exposure. We implemented optical waveguide in our probes to guide light from a laser source to the tip of the probe and manipulate the neural activity. Furthermore, we fabricated micro-channels within the device to enable focal drug delivery at the tip of the device. Using the T-DOpE probe, we studied the effect of local synthetic cannabinoid injection in the hippocampus. We found that the local injection of the drug in hippocampus CA1 makes neurons incapable of generating sharp wave-ripples (a neural signal associated with memory). Electroporation is a biophysical phenomenon where short high electric field pulses introduce nanoscale defects in cell membrane. These defects can cause unstable cellular homeostasis and eventually leads to cell death. Due to reduced treatment time, no heat effect, and tissue selectivity, electroporation has been used in clinical trials for cancer treatments. Using the thermal drawing process and laser micromachining techniques, we developed a flexible microscale electroporation fiber probe capable of ablating tumor cells. Due to the low-cost and scalability of thermal drawing process, we envision the use of thermally drawn functional fiber technology in biomedical fields. In this dissertation, I also address some challenges and future directions of thermally drawn functional fibers in biomedical fields.