Research On Implantable Artificial Neural System For Paralysis Recovery Based On Flexible MEMS Microelectrodes Modified By Conducting Polymer

Increasing population of patients suffer from spinal cord injury(SCI) induced by physical damage and organic disease world-widely every year. As significant path for order delivery of central nerve system, spinal cord injury would directly lead to extensive body paralysis of patients. Therefore, the most direct and urgent desire for paralyzed patients is to quickly rebuild their motor function in a secure and efficient way. The main idea of many researches on paralysis recovery treatments is to rebuild motor nerve system via replacing damaged motor nerve by an artificial nerve system. The rapid development of Micro-Electro-Mechanical System(MEMS) technology accelerates the development pace of the miniaturization and multi-functionalization of the implantable artificial neural system. Comparing with other technologies, the advantages that MEMS technology exhibited include: small size, light weight, high reliability, low power consumption, low cost, excellent functionality as well as flexible combination with biotechnology and molecular biology.The existing problems and drawbacks of implantable artificial neural system for paralysis recovery include three aspects: 1. the implantable microelectrodes fabricated by MEMS technology possessed relatively poor flexibility and multi-functionality, which could hardly act as multi-functional chronic implants to match with the inherent characteristic of dynamic living biological tissue; 2. the overall efficacy of the implantable artificial neural system was severely restricted by relatively poor performance of the electrode-tissue interface, and novel electrode-tissue interface with excellent efficiency, stability and safety was expected to be developed; 3. as the most direct and efficient way for paralysis recovery, the research on current pulse stimulation of skeletal muscle for motor function restoration by using the implantable artificial neural system was inadequate. In order to solve the problems and drawbacks mentioned above, this paper mainly focuses on the study of implantable artificial neural system for paralysis recovery, which is composed of the flexible MEMS microelectrodes developed by MEMS technology and modified by conducting polymer. The main research work is described as follow:1. Two kinds of novel multi-functional flexible MEMS microelectrodes that integrated with micro channel for fluidic drug delivery were developed, which comprised: integrated flexible MEMS microelectrode and winding flexible MEMS microelectrode. The preparation methods and processing parameters of both kinds of microelectrodes were studied, and the repetition rate and cost of the fabrication processes were high and low, respectively. The both kinds of microelectrodes which made of flexible biocompatible materials were capable to adapt to dynamic biological tissue environment. The unique three-dimensional structure of the electrode sites distribution enhanced the spatial selectivity comparing with the traditional microelectrodes. The both kinds of microelectrodes were electrochemically deposited with conducting polymer to improve their electrochemical performance, including: electrochemical impedance and charge storage capacity(CSC). The mechanical performance, stability and fluidic resistance of both kinds of microelectrodes were tested and analyzed. The practicability of the developed microelectrodes was studied by in vivo electrophysiological experiments, including: electromyography(EMG) signal recording and drug delivery through micro fluidic channel. It was easy for both kinds of the developed microelectrodes to be implanted to target biological tissue by simple surgery process. Both kinds of the developed microelectrodes were able to stimulate electro-active tissue and record electrophysiological signal while conducting biochemical modulation by controlled drug delivery. This study provided new ideas and approaches for multiple aspects of research on paralysis recovery, deep brain stimulation and function monitoring and modulation of tissue and organs in the future.2. The multi-aspect performance of conducting polymer poly(3,4-ethylenedioxythiophene)(PEDOT) composite electrode-tissue interface doped with three different kinds of biotic molecules and three different kinds of abiotic molecules was compared and studied systematically. The synthesis process of each biotic/abiotic molecules doped PEDOT electrode-tissue interface was studied, respectively. Their surface morphology and characteristics were also characterized and studied by multiple kinds of microscopic observation technologies. The electrochemical performance of each biotic/abiotic molecules doped PEDOT electrode-tissue interface was studied, including: electrochemical impedance spectrum(EIS), charge storage capacity(CSC) and charge injection limit. The electrochemical and electrical stimulation stability of each biotic/abiotic molecules doped PEDOT electrode-tissue interface was studied and analyzed by repeated cyclic voltammetry scanning and current pulse stimulating, respectively. The biocompatibility of the six kinds of biotic/abiotic molecules doped PEDOT electrode-tissue interface was studied and analyzed by cells cultivation on their surfaces. The systematic and comprehensive study on the performance of the six kinds of biotic/abiotic molecule doped conducting polymers provided research basis to future development and application of conducting polymer.3. The graphene oxide(GO) doped conducting polymer PEDOT composite electrode-tissue interface was developed. The synthesis process of the GO doped PEDOT electrode-tissue interface was studied. Its surface morphology characteristics were studied by scanning electron microscopy(SEM), transmission electron microscopy(TEM) and atom force microscopy(AFM). The specific area and charge transfer rate of the electrode-tissue interface was significantly improved due to the unique composite structure consisted of single atom layer graphene oxide that overlapped with each other in three-dimension space and conducting polymer filled in it. The chemical structure and characteristic of the GO doped PEDOT electrode-tissue interface was characterized and analyzed by X-ray photoelectron spectroscopy(XPS), Fourier transform infrared spectroscopy(FTIR) and UV-Vis spectra(UVI). The electrochemical performance of the GO doped PEDOT electrode-tissue interface was studied, including: electrochemical impedance spectrum(EIS), charge storage capacity(CSC) and charge injection limit. Its electrochemical stability was also studied and analyzed. The biocompatibility of the GO doped PEDOT electrode-tissue interface was studied and analyzed by cells viability, cells proliferation and cells attachment tests. The unique ridge-like surface morphology and excellent electrochemical performance and biocompatibility of the developed novel PEDOT/GO composite electrode-tissue interface facilitated its extensive application in research area of implantable microsystem, tissue engineering and controlled drug release.4. The multi-area and multi-parameter electrical stimulation of rat skeletal muscle model for paralysis recovery was studied through in vivo electrophysiological experiments by the developed implantable artificial neural system. Based on the research and analysis of the movement mechanism of skeletal muscle, the electrochemical process of biomedical electrical stimulation and the charge injection through electrode-tissue interface during electrical stimulation process, the effective and secure electrical stimulation mode of current pulses was chosen. The muscle contraction force model of direct current pulse stimulation to skeletal muscle was studied and proposed, and the muscle contraction force distribution curve under electrical stimulation was demonstrated by the model fitting. The multi-area electrical stimulation efficacy, the multi-area muscle response characteristic to different stimulation frequencies and the multi-area muscle response characteristic to different stimulation amplitudes were studied and analyzed. Furthermore, the recruitment curves of rat tibialis anterior(TA), gastrocnemius(GA), rectus femoris(RF) and vastus lateralis(VL) under current pulse stimulation were summarized and obtained by Sigmoid curve fitting of the multi-area muscle response characteristic to different stimulation amplitudes. The regularity results of paralysis recovery though direct electrical stimulation to skeletal muscle by using implantable artificial neural system were obtained by studying and summarizing of multiple response characteristic of multiple skeletal muscles.