| Paralysis caused by spinal cord injury or neuropathy can cause significant impacts on the patients' daily life.To fulfil the urgent need of paralysis rehabilitation,domestic and foreign research institutions have committed to the study of rehabilitation.One of the popular research subjects in the field of paralysis rehabilitation is the implantable artificial neural system based on MEMS(Micro-Electro-Mechanical Systems)technology.At present,the rapid development of MEMS provides the possibility for the miniaturization and integration of implantable artificial neural system.With the continuous progress of technology,the implantable artificial neural system based on MEMS neural interface devices,has the potential to reconstruct the motor function of skeletal muscles,and achieves a certain degree of paralysis rehabilitation.In 2012,Nicholas A.Kotov and Daryl R.Kipke et al in the paper published in “NATURE MATERIALS” entitled “Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces” mentioned that the neural interface device is a critical technology for electrical stimulation and recording of excitable tissue across basic and applied neuroscience.In 2008,Stuart F.Cogan in the review paper published in “Annual Review of Biomedical Engineering” entitled “Neural Stimulation and Recording Electrodes”and in 2005,Daniel R.Merrill et al in the review paper published in “Journal of Neuroscience Methods” entitled “Electrical stimulation of excitable tissue: design of efficacious and safe protocols”also talk about that the neural interface device is the bridge of ionic conduction mechanism for biological tissues and electronic conduction mechanism for artificial system.The performance of neural interface devices determines the overall effectiveness of the implantable artificial neural system for paralysis rehabilitation.On the basis of domestic and foreign related research,this work mainly focused on the flexible neural interface devices of implantable artificial neural system for paralysis rehabilitation.The planar and three-dimensional flexible MEMS neural interface devices are modified by iridium oxide,and their recording and stimulation areas are controllable due to the optimized design.The molecular mechanisms of the motor reconstruction of muscle fibers by flexible neural interface devices are also studied.The main work is as follows:1.The modeling,simulation and optimization of MEMS neural interface devices were carried out.By the special design of neural interface devices that the stimulation(or recording)sites were surrounded by eight ground(or reference)sites,the MEMS neural interface device which was capable of electrophysiological recording and electrical stimulation of controlled area was obtained.For electrical stimulation,the stimulation sites were surrounded by eight ground sites which could restrict the current distribution inside the grid area and had tiny effect on the tissue outside the grid.On the other hand,for electrical recording,the recording sites were surrounded by eight reference sites which could restrict the area of recorded voltage distribution.It can only record the electrical activities inside the grid area and block effect of the tissue outside the grid.2.Iridium oxide as a modifying material of neural interface has been systematically developed and optimized.For the electrochemical modification of flexible neural interface device,three kinds of iridium oxide were developed,including activated iridium oxide film(AIROF);sputtering iridium oxide film(SIROF);electrodeposited iridium oxide film(EIROF).We have studied the detailed activation process of the AIROF microelectrodes from the iridium microelectrodes.The relationship between the electrochemical performance of the AIROF microelectrodes and the applied activation cycles is also investigated.AIROF has the stable and small phase shift,it is more suitable for the application of neural signal recording.For SIROF,we have investigated the effect of the oxygen flow under various sputtering pressure on microstructure and electrochemical properties of the iridium oxide thin film,aiming to achieve a stable and high CSC electrochemical material for microelectrodes in electrical stimulation applications.The adhesion between SIROF and substrate is good and it shows good stability.Therefore,it is suitable for long-term use in the neural interface devices.At last,we have studied the EIROF which is fabricated by an electrodeposition process from a solution containing a suitable iridium complex.EIROF has a large charge storage capability and a low impedance.It is more suitable for the applications of short time electrical stimulation and recording.3.Two flexible planar and three-dimensional MEMS neural interface devices are developed as follows: EIROF modified self-closed neural cuff device and SIROF modified planar neural interface device.The preparation methods of cuff electrodes closure structures are relatively complex,and these devices have large size,which limits their practical application.To solve the problem,the self-closed neural interface device with simple cuff closed structure,high flexibility and integration has been developed.The difference of annealing times produces the mismatch of residual stresses and thermal stress,which results in both direct tension and bending stress on the two Parylene layers.Thus,it is the spiral source of the self-closed Parylene cuff electrode.Furthermore,it is modified by EIROF which can enhance the electrochemical performances.By depositing the SIROF with appropriate conditions on the pre-annealed Parylene layers,the SIROF modified flexible Parylene microelectrodes have been successfully fabricated.Combining the advantages of Parylene as the structural material and SIROF as the good electrochemical modification material,the SIROF modified planar neural interface device showed remarkable performances.4.The preliminary animal experiments were conducted to validate the feasibility of the two neural interface devices for electrical recording and stimulation.EIROF modified self-closed neural interface device has good electrochemical performances and self-closed structure.Therefore,the mechanical pressure applied on a nerve is very small,relative to the closure pressure of traditional mode.Due to the special design that the recording channels were surround by the reference channel,the electrocardiogram(EKG)and electromyogram(EMG)could be directly shielded and blocked.The effects of EKG and EMG on the compound action potential(CAP)recording could be significantly reduced.The electrochemical performances of the SIROF planar neural interface device can be maintained and the stability is also good.Due to the special design that the recording channels were surround by the reference channel,the stimulation-induced artifacts could be directly blocked.Due to the special design that the stimulation sites were surrounded by eight ground sites,the stimulation current was restricted inside the grid.The different stimulation channels worked independently.According to the different stimulated channels,there were a lot of leg movements that could be modulated.The preliminary animal experiments validated the feasibility of SIROF microelectrode in electrical stimulation based on the three-axis force responses and torque responses.The present neural interface device is promising to be used for paralysis rehabilitation.5.The molecular level evidences of skeletal muscle for paralysis recovery were in vivo investigated.In the synchrotron radiation conditions,different types of neural interface devices have been used for stimulation of rat leg muscles.At the same time,the X-ray diffraction data of muscle fibers under the different stimulation conditions were collected.The results showed that the stimulation frequency of 75 Hz had the strongest intensity of myosin heads movement and was most resistant to fatigue at the molecular level.The neural interface devices which can inject the current closest to the natural conditions of motoneuron activation will have a best stimulation results.Based on this theory,these results make the microelectrode array a good candidate for better muscle stimulation. |
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