Basic Investigation On The Applications Of Implantable Neural Electrodes

Electrical neural microstimulation and recording with implanted devices in vivo are increasingly being applied in research instruments and medical devices, such as brain-machine interface and neural prostheses. These works aim to understand neural system and restore motor or sensatory function in the case of paralysis and sensory defects, which are a great scientific challenge in this century. The rapidly expanding researches and developments require advanced neural electrode technology that is reliable and efficient in living body for a long period of time.However, there are two major problems hindered the clinical applications of implantable neural devices, one is the electrochemical performance of the neural microelectrodes, and the other is the inconsistent performance caused by tissue responses. This work aimed to develop neural electrodes and electrode/neural interfaces to improve the electrochemical performance and biocompatibility. The main works and new findings are summarized as followings:1. An efficient and reliable electrochemical method for preparation of activated iridium oxide films (AIROF) microelectrodes by applying an asymmetric pulse train in Na2HPO4 solution was achieved. The AIROF microelectrodes exhibited a very high safe charge injection (Qinj) limit of～4.1 mC/cm2, as well as excellent mechanical and electrochemical stability. Electrode impedance at 1 kHz has been significantly reduced by～92% for the electrodes with diameter of 100μm. All of these characteristics are greatly desirable for electrical neural microstimulation and recording applications.However, as iridium metal is very hard and brittle with low ductility and making Ir electrode substrate usually require complicated sputtering facility, so growth AIROF on Ir electrode substrate is cost and inconvenience. An alternative and more efficient method for preparing electrodeposited iridium oxide films (EIROF) microelectrodes is developed. The EIROF microelectrodes exhibited high safe charge injection limits of ～2.6mC/cm2, and the electrode impedance at 1 kHz was significantly reduced by～92% (electrode diameter=100μm). The EIROF microelectrodes also have shown good mechanical and electrochemical stability, as well as an excellent super-Nernstian slope in a broad pH range (1～13). This electrodepositing method can be more facilely incorporated into thin-film technology and Microelectromechanical Systems (MEMS).2. The search for new electrode materials including new electrode modification methods is crucial for improving long-term performance of neuroprosthetic devices. In this study, an investigation of electrochemically co-deposited polypyrrole/single-walled carbon nanotube (PPy/SWCNT) films for improving the electrode-neural interface was carried out. The PPy/SWCNT microelectrodes exhibited a particularly high safe charge injection limit of～7.5 mC/cm2 and low electrode impedance at 1 kHz, as well as good stability. Cells attachment and neurite outgrowth of rat pheochromocytoma (PC 12) cells on the PPy/SWCNT deposited substrates were clearly observed by Calcein-AM staining and scanning electron microscope (SEM) analysis. Furthermore, tissue response was studied by a 6-week implantation in the cortex of rats. A significantly lower (P< 0.05) glial fibrillary acidic protein (GFAP) and higher (P< 0.05) neuronal nuclei (NeuN) immunostaining were found on comparison of the test group (n= 11) with the control group (n= 8), in the zone within the distance of 100μm to the implant interface. These characteristics are desirable for chronically implantable neural probes with high density microelectrodes. More importantly, this technique can easily incorporate other modification methods to build a more advanced electrode-neural interface.3. A major problem which hinders the applications of neural prostheses is the inconsistent performance caused by tissue responses during long-term implantation. In this study, we investigated a new approach, applying hydrogel coating, for improving the electrode-neural tissue interface. Hydrogel poly(vinyl alcohol)/poly(acrylic acid) interpenetrating polymer networks (PVA/PAA IPN), Polyurethane (PU), and poly(vinyl alcohol)/polyurethane (PVA/PU) were synthesized and tailored as coatings for poly-(dimethylsiloxane) (PDMS) based neural electrodes with the aid of plasma pretreatment. Changes in the electrochemical impedance and maximum charge injection limits of the coated iridium oxide microelectrodes were negligible. Protein adsorption on PDMS was reduced by 85%～92% after coating. In the presence of nerve growth factor (NGF), neurite extension of rat pheochromocytoma (PC12) cells was clearly greater on coated films than on PDMS substrates. Furthermore, after 6-week implantation in the cortex of rats, the tissue responses of coated PDMS implants were significant improved than the uncoated PDMS implants, confirmed by lower GFAP and higher NeuN immunostaining around the implantation sites. All of these results suggest that the hydrogel coating is feasible and favorable to neural electrode applications.