基于柔性MEMS的可植入人工面神经技术研究

发布时间：2018-04-23 05:13

本文选题：MEMS + 人工面神经　；参考：《上海交通大学》2014年博士论文

【摘要】：面神经受损时会引起面部肌肉麻痹或者瘫痪，使患者失去面部功能。面神经受损不仅影响人面部的美观，还可导致脸部器官不能正常工作，其中较为严重的症状是使患者无法闭目，从而使眼球失去眼睑的保护并且无法对眼球进行湿润，这将导致失明，它严重影响了人们的正常生活。目前，治疗面神经障碍的方法主要有神经移植、器械辅助和电刺激等。神经移植疗法由于可移植神经数量少、术后可能引起并发症以及人工神经材料生物相容性不佳等原因导致其在临床中受到限制，且此方法对神经受损严重的患者治愈的几率很小。器械辅助方法也由于其使用不方便、美观性和效用性差等原因而受到限制。电刺激可使瘫痪肌肉收缩，被广泛应用于功能性电刺激和治疗性应用中。通过在面神经受损患者面部植入微机械电子系统（MEMS）对肌肉进行功能性电刺激（FES），，将有助于面神经受损严重的患者恢复面部功能。本文围绕基于电刺激的人工面神经修复技术开展研究工作，在国内外相关研究工作的基础上，提出了一种基于柔性MEMS的植入式人工面神经技术，主要包含了柔性MEMS技术、微电极技术、系统集成技术、系统供能技术及电刺激技术等关键技术。研究面神经治疗系统的框架以及各关键技术在该系统中所起的作用，并研究基于这些关键技术的系统各组成部分的器件的设计和制备工艺，并对制备的器件进行了性能测试和相关动物实验。论文的主要工作如下： 1、研究了一种基于Parylene的具有多点刺激功能的铂黑丝状微电极，研究了丝电极的制备工艺。在电极制备过程中，采用生物相容性好的铂作为电极材料，Parylene为封装材料，使用lift-off工艺简单有效地制备了多电极点丝电极。研究了通过电极表面修饰技术来优化电极电化学性能。使用基于超声辅助的电流脉冲电镀铂黑镀层于电极点上，进一步降低了电极阻抗，增加了电荷存储容量，同时增加镀层与基底结合力，提高了机械稳定性。在超声衰减测试中，相比传统的直流电镀的铂黑电极，基于超声辅助的脉冲电流电镀的铂黑电极阴极电荷注入容量的衰减量只有前者的三分之一。且经过2.19×108个电脉冲老化后，其阴极电荷注入容量几乎不变，显示了较好的电化学稳定性。并且在电极折弯实验中也显示了较好的折弯稳定性。研究了电极加速老化模型。在加速老化实验中，电极保持在87℃生理盐水中8个月，与保持在人体内环境下21年的时间相当，其阻抗与阴极电荷注入容量在实验后期保持相对稳定，显示了电极长期植入后具有较好的稳定性。并对铂黑电极进行了生物相容性实验。铂黑电极植入兔肌肉中两周后，其组织反映与铂电极相同，显示了其具有较好的生物相容性。 2、研究了一种基于Parylene的半球凸起微电极阵列。研究了三维凸起微电极阵列的制备工艺。在微电极阵列的制备过程中，使用了MEMS技术及光刻胶热熔回流技术控制电极形貌。对模型进行了相关的电学和力学仿真。为了改善其电化学性能，同样在电极点上进行了基于超声辅助的脉冲电流电镀铂黑的方式来进行电极表面修饰。并且对制备出的半球凸起电极进行了阻抗测试，结果表明半球凸起电极较同底面积的平面电极有更小的阻抗。 3、研究了一种基于柔性MEMS技术的芯片电极多层互连技术。研究了芯片电极多层互连结构的制备工艺。采用了基于PDMS为基底的芯片电极多层互连方法，系统集成度高，尺寸小。相比传统的单层互连结构，多层互连结构单位面积上互连电极数量多，使用聚合物PDMS作为基底材料，节约工艺成本，绝缘层为绝缘性能良好的具有较好柔性Parylene薄膜，可使制备的互连结构具有一定的柔性。 4、研究了基于透皮方式的体内充电技术。分别设计并制备了基于单针和双针插头的植入式体内供能装置。在基于单针插头的植入式体内供能装置的设计与制备中，使插座内的双层金属网与针状插头形成过盈配合，实现了在整个金属网区域均可给植入体内的电池充电。在使用不同角度将插头插入电池单元过程中，接触电阻均小于1，显示了较高的连接可靠性。且通过植入生物组织后，将针透过皮肤插入插座单元，能有效测量出电池电压，显示了操作的方便性。具备较好柔性的PDMS封装外壳在插头刺入多次后仍能保持其良好的防水性，以阻止体液的渗透给系统带来损害。另外，较小的刺入力进一步显示了充电过程的方便性。在基于双针插头的植入式体内供能装置的设计与制备中，使插座内的两片金属网位于同一平面上，并在充电时与双针插头同样形成过盈配合，这样可以减小器件厚度，且其同样具备基于双针插头的植入式体内供能装置的特性。 5、研究了刺激与采集相关技术，主要包括实现刺激与采集功能的系统框架及其硬件电路的实现形式。进行了肌电信号采集和肌肉刺激的动物实验。在肌电信号采集的动物实验中，使用了三组具有不同电极点面积的电极对同一只兔子的同一个眼轮匝肌位置分别进行兔持续闭眼、持续眼以及诱发闭眼三种状态下的肌电信号的采集。然后对每种状态下的不同组电极采集到的信号进行时域和频域的分析比较，得出电极点面积较大的电极采集到的肌电信号的幅值和功率都较大。并且，利用一组采集电极从同一只兔子的同一眼轮匝肌位置上采集兔自然持续闭眼、自然持续睁眼、自然眨眼以及诱发闭眼四种状态下的肌电信号。然后对信号进行时域和频域的信号处理，观察不同兔眼动作状态下的肌电信号的区别和联系，结果显示，诱发闭眼的肌电信号的幅值和功率都较其它三种状态大。在电刺激动物实验中，使用电荷不平衡双向电流脉冲分别对兔眼轮匝肌进行了开环和闭环电刺激，达到了较好的效果。
[Abstract]:When facial nerve is damaged, facial muscle paralysis or paralysis can cause the patient to lose facial function. The damage of facial nerve not only affects the beauty of the face, but also causes the facial organs to not work properly. The more serious symptoms are that the patients can not close their eyes, so that the eyeball is lost to the protection of the eyelids and can not be moist to the eyeball. This will lead to blindness, which seriously affects people's normal life. At present, the main methods of treating facial nerve disorders are neural transplantation, instrument assistance and electrical stimulation. The treatment of nerve transplantation is due to the low number of transplantable nerves, the possible complications after the operation and the poor biocompatibility of artificial nerve materials. It is limited, and this method is less likely to be cured for patients with severe nerve damage. Instrument assistance is also limited by its inconvenient use, beauty and poor utility. Electrical stimulation can constriction paralyzed muscles, and is widely used in functional electrical stimulation and treatment applications. Through the face of patients with impaired facial nerve. Functional electrical stimulation (FES) by intramuscular microelectromechanical system (MEMS) will help facial nerve function recovery in patients with severe facial nerve injury.
In this paper, based on the research of artificial facial nerve repair technology based on electrical stimulation, based on the relevant research work at home and abroad, a kind of implant artificial facial nerve technology based on flexible MEMS is proposed, which mainly includes flexible MEMS technology, microelectrode technology, system integration technology, system energy supply technology and electrical stimulation technology. To study the framework of facial nerve treatment system and the role of various key technologies in the system, and to study the design and preparation process of the components of the system based on these key technologies, and perform performance testing and related animal experiments on the fabricated devices. The main work of this paper is as follows:
1, a platinum black filamentous microelectrode with multi point stimulation based on Parylene was studied. The preparation process of the wire electrode was studied. In the preparation of the electrode, the biocompatible platinum as the electrode material, the Parylene as the packaging material and the lift-off process were used to prepare the multi electrode point wire electrode. The electrode electrochemical performance is optimized by the electrode surface modification technology. Using the ultrasonic assisted electroplating platinum black coating at the electrode point, the electrode impedance is further reduced, the charge storage capacity is increased, and the bonding force between the coating and the substrate is increased and the mechanical stability is increased. In the ultrasonic attenuation test, compared with the traditional direct current electroplating The cathodic charge injection capacity of the platinum black electrode based on ultrasonic assisted electroplating is only 1/3 of the former, and after 2.19 x 108 electrical pulses aging, the charge injection capacity of the cathode is almost invariable, which shows good electrochemical stability and is also better in the electrode bending experiment. The electrode accelerated aging model was studied. In the accelerated aging test, the electrode remained at 87 centigrade saline for 8 months, which was equivalent to 21 years in the internal environment. The impedance and the cathode charge injection capacity remained relatively stable in the late experiment, which showed that the electrode had good stability after long-term implantation. The biocompatibility of platinum black electrode was tested. After two weeks in rabbit muscle, platinum black electrode showed the same tissue as platinum electrode, which showed that it had better biocompatibility.
2, a spherical convex microelectrode array based on Parylene was studied. The preparation process of a three-dimensional convex microelectrode array was studied. In the preparation of microelectrode array, MEMS technology and photoresist reflux technique were used to control the electrode morphology. The electrical and mechanical simulation of the model was carried out to improve the electrochemical performance of the model. The electrode surface modification was carried out at the electrode point based on the ultrasonic assisted electroplating platinum black. The impedance test was carried out on the prepared hemispherical convex electrode. The results showed that the hemispherical convex electrode had smaller impedance than the flat surface electrode with the same floor area.
3, a multilayer chip electrode interconnect technology based on flexible MEMS technology is studied. The fabrication process of multilayer interconnect structure of chip electrode is studied. The multilayer interconnection of chip electrode based on PDMS is used. The system has high integration degree and small size. Compared with the traditional single layer interconnect structure, the interconnect electrode per unit area of multilayer interconnection structure is connected to the interconnect electrode. The number is more, the polymer PDMS is used as the base material, and the process cost is saved. The insulating layer has good flexible Parylene film with good insulation performance, which can make the interconnect structure prepared with a certain flexibility.
4, the body charging technology based on the transdermal mode was studied. The implantable energy supply device based on single needle and double pin plug was designed and prepared respectively. In the design and preparation of an implantable body based energy supply device based on single pin plug, the double layer metal net in the socket and the needle like plug were formed in the interference, and the whole metal net was realized. The area can charge the battery for the implanted body. The contact resistance is less than 1 in the process of inserting the plug into the cell unit with different angles. It shows the high reliability of the connection. And the insertion of the needle through the skin through the skin can effectively measure the voltage of the electric pool and show the convenience of the operation. The flexible PDMS enclosure can maintain its good waterproof property after the plug is inserted many times to prevent damage to the system from the penetration of the body fluid. In addition, the smaller thrust force further demonstrates the convenience of the charging process. In the design and preparation of an implantable device based on a double pin plug, two pieces of metal in the socket are made. The net is on the same plane and forms a interference fit with the double pin plug when charging, which can reduce the thickness of the device, and it also has the characteristics of an implantable energy supply device based on a double pin plug.
5, we studied the related techniques of stimulation and acquisition, mainly including the system framework for the realization of the function of stimulation and acquisition and the realization of the hardware circuits. In the animal experiments of the EMG signal acquisition, three groups of electrodes with the area of different electric poles were used for the same rabbit. In the same position of the orbicularis oculi muscle, the EMG signals were collected in three states of continuous closed eyes, continuous eyes and induced closed eyes respectively. Then the signals collected by different groups of electrodes in each state were analyzed and compared in time domain and frequency domain, and the amplitude and power of electromyographic signals collected by electrodes with larger electrode area were obtained. In addition, the spontaneous closed eyes of rabbits were collected from the same orbicularis oculi muscle of the same rabbit with a set of collecting electrodes. The EMG signals were naturally kept open, natural blinked and induced in four states of closed eyes. Then the signal was processed in time and frequency domain to observe the EMG signals under the action state of different rabbit eyes. The results show that the amplitude and power of the EMG signals are larger than those of the other three states. In the experiment of electric stimulation, the open and closed loop electric stimulation of the orbicularis orbicularis muscle of rabbit eye is carried out by using the charge imbalanced bi-directional current pulse, and the better effect is achieved.

【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R318.1;R651.3

【参考文献】