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.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/112751 |
| Date | 08 June 2021 |
| Creators | Jiang, Shan |
| Contributors | Electrical Engineering, Jia, Xiaoting, Wang, Anbo, Zhou, Wei, Sontheimer, Harald W., Li, Qiang |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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