Electrodes made of stainless steel, noble metals and crystalline silicon have been widely used for neural recording and neural stimulation in neuroscience study and clinical application. However, the high stiffness and large size of these electrodes challenges their capability of forming chronically stable neural-electrode interfacing for reliable and stable neural recording and stimulation. What’s more, these electrodes may cause magnetic field distortions and introduce large blind areas around the electrodes during magnetic resonance imaging (MRI), while MRI allows global brain activity detection and serves as an important and commonly used tool in neuroscience researches and clinical applications. Therefore, a neural electrode that integrates MRI compatibility and forms stable chronic neural interface for neural recording and stimulation is highly desired. Carbon nanotube (CNT) fiber is an excellent material candidate for the purpose due to its high softness, excellent electrochemical properties and close-to-tissue magnetic susceptibility. The aim of the thesis study is to develop soft and ultrasmall CNT fiber based neural electrodes for multimodal neural interfacing, such as MRI study, neural recording, etc. The thesis developed the fabrication and implantation technologies of standalone CNT fiber electrodes, demonstrated their electrochemical properties, mechanical compliance in vitro and biocompatibility in vivo, examined and explained their MRI compatibility in vivo, explored their multiple advantages for acute and chronic neural recording in vivo. The main accomplishments are as follows: Fabrication, implantation technologies and characterization of CNT fiber electrodes. CNT fibers were fabricated from millions of tiny CNTs and coated with parylene-C via chemical vapor deposition for insulation, followed by blade cutting on the fibers for exposing the recording sites. A shuttle-assisting method was utilized for implantation, where CNT fiber electrodes were initially combined with stiff tungsten wires by gluing with biocompatible and dissolvable adhesive polymer materials, then being inserted together with the tungsten wire which acted as a shuttle, and finally the tungsten shuttle was extracted out, leaving CNT fiber electrodes inside. The nitric acid treated CNT fiber electrodes showed 0.11 times, 178 times, and 34 times the impedance, charge storage capacity and charge injection limit respectively of PtIr electrodes of a similar size. The low impedance favors for neural recording. And the high charge storage capacity and high charge injection limit favor for neural stimulation. The bending stiffness per width were 8.16k nN·m, 0.16k nN·m, 153k nN·m, 39k nN·m and 460k nN·m respectively for 20μm CNT fiber electrodes, 5 μm CNT fiber electrodes, PtIr electrodes, carbon fiber electrodes and silicon electrodes. The orders of magnitude smaller bending stiffness demonstrated the softness of CNT fiber electrodes, favorable for reducing tissue damage, mitigating inflammatory responses and facilitating chronic stable neural interface. The histological studies at 6-week post electrodes implantation showed 2-fold reduction compared to PtIr electrodes for the accumulated astrocytes and activated microglia, which are inflammatory cells activated during foreign body reaction. The neuron lost zone of CNT fiber electrodes was 40% smaller than that of PtIr electrodes. The results at 12-week post implantation of PtIr electrodes showed further neurodegeneration with 1.3-fold neuron lost zone increase while no significant further degeneration in the vicinity of CNT fiber electrodes. Therefore, the CNT fiber electrodes manifested improved and more stable chronic neural interfacing, facilitating chronic studies on neural activities. Standalone CNT fiber electrodes demonstrated MRI compatibility.20 μm diameter CNT fiber electrodes in T2-weighted anatomical images under 7.0 T MRI scan showed an artifact size 40% of that from PtIr electrodes with a similar electrode size. Besides, the CNT fiber electrodes were barely visible in T1-weighted MRI scanning, compared to 922 μm artifact size around the PtIr electrodes. The main reason accounting for CNT fiber electrodes’ better MRI compatibility is their much closer magnetic susceptibility to tissue. Though the eddy currents in both electrodes, which may contribute to the artifacts, are quite small and disappear fast, the calculation showed that the CNT fiber electrodes have ~ 1% eddy current amplitude, ~ 1% current decaying time constant and ~ 1/10 skin depth compared with those of the PtIr electrodes. Therefore, the CNT fiber electrodes exhibited much superior MRI compatibility, favoring and enabling many applications, such as verification and adjustment of the implantation position of deep brain stimulating electrodes with MRI, mapping large-scale neural activity from functional MRI with electrophysiological recording results with high temporal and spatial resolution, localization of seizure foci for clinical treatment, etc. Acute and chronic neural recordings in vivo. Representative single unit neural signals responding to whisker stimulation recorded in ventral posteromedial (VPm) thalamic nucleus in rats demonstrated the ability of CNT fiber electrodes for precisely targeting planned brain areas in the brain as VPm area is small (~ 1-2 mm) and deep (~5 mm) in the brain. Other recordings in the somatosensory area of S1 served as a good justification of the CNT fiber electrodes’ single unit signal detection sensitivity, as the relatively smaller spikes amplitude generated from neurons in S1 requires higher electrical detection sensitivity. The multi-depth electrophysiological recording results demonstrated the CNT fiber electrodes’ ability of fine-tuning the implantation position of the microelectrodes after implantation, which offers advantage for both recording and stimulating neural electrodes. Note that many state-of-the-art flexible electrodes require about 2 weeks for tissue recovery after implantation before the first successful electrophysiological recording, while the CNT fiber electrodes obtain real time electrophysiological recording during implantation. What’s more, many flexible electrodes lack the capability of fine-tuning of implanted position or the implantation are constrained within a very shallow depth, the CNT fiber electrodes are robust enough to be fined-tuned and a 7 mm implantation depth is attainable, enabling deep brain study. The chronic recording examples showed the longevity of the CNT fiber electrodes for stably recording single unit signals for 4-6 months without repositioning. To further analyze the electrophysiological recordings, principal component analysis was performed, and four different features of the sorted single units were calculated. These analyses manifested that some of the recorded single units from that rat recorded for 4 months were possibly from the same neuron, which demonstrated the potential of CNT fiber electrodes for tracking same neurons, favoring many fundamental neuroscience studies, such as investigating the mechanisms of aging of neurons, studying the action potential firing changes of neurons with repeated stimulation, etc. In addition, ultrasmall electrodes made with 5 μm diameter CNT fiber cores were achieved and the single unit recording capability was verified in vivo. The ultrasmall sized CNT fiber electrodes allow for high spatial recording resolution, low tissue damage and mild inflammatory responses, and more electrodes being integrated in a limited space. Conclusion: The thesis extensively explored the possibilities of soft CNT fiber electrodes, which showed multiple excellent advantages for multimodal neural interface. The thesis study laid the foundation for further exploration and development of CNT fiber based neural interface, and provided an outstanding tool for future neuroscience study, brain-computer-interface research and clinical application.
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Soft carbon nanotube fiber electrodes for multimodal neural interfacing
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