本文選題：MEMS + 人工面神經(jīng)�。� 參考：《上海交通大學(xué)》2014年博士論文

【摘要】：面神經(jīng)受損時(shí)會(huì)引起面部肌肉麻痹或者癱瘓，使患者失去面部功能。面神經(jīng)受損不僅影響人面部的美觀，還可導(dǎo)致臉部器官不能正常工作，其中較為嚴(yán)重的癥狀是使患者無法閉目，從而使眼球失去眼瞼的保護(hù)并且無法對(duì)眼球進(jìn)行濕潤，這將導(dǎo)致失明，它嚴(yán)重影響了人們的正常生活。目前，治療面神經(jīng)障礙的方法主要有神經(jīng)移植、器械輔助和電刺激等。神經(jīng)移植療法由于可移植神經(jīng)數(shù)量少、術(shù)后可能引起并發(fā)癥以及人工神經(jīng)材料生物相容性不佳等原因?qū)е缕湓谂R床中受到限制，且此方法對(duì)神經(jīng)受損嚴(yán)重的患者治愈的幾率很小。器械輔助方法也由于其使用不方便、美觀性和效用性差等原因而受到限制。電刺激可使癱瘓肌肉收縮，被廣泛應(yīng)用于功能性電刺激和治療性應(yīng)用中。通過在面神經(jīng)受損患者面部植入微機(jī)械電子系統(tǒng)（MEMS）對(duì)肌肉進(jìn)行功能性電刺激（FES），，將有助于面神經(jīng)受損嚴(yán)重的患者恢復(fù)面部功能。 本文圍繞基于電刺激的人工面神經(jīng)修復(fù)技術(shù)開展研究工作，在國內(nèi)外相關(guān)研究工作的基礎(chǔ)上，提出了一種基于柔性MEMS的植入式人工面神經(jīng)技術(shù)，主要包含了柔性MEMS技術(shù)、微電極技術(shù)、系統(tǒng)集成技術(shù)、系統(tǒng)供能技術(shù)及電刺激技術(shù)等關(guān)鍵技術(shù)。研究面神經(jīng)治療系統(tǒng)的框架以及各關(guān)鍵技術(shù)在該系統(tǒng)中所起的作用，并研究基于這些關(guān)鍵技術(shù)的系統(tǒng)各組成部分的器件的設(shè)計(jì)和制備工藝，并對(duì)制備的器件進(jìn)行了性能測(cè)試和相關(guān)動(dòng)物實(shí)驗(yàn)。論文的主要工作如下： 1、研究了一種基于Parylene的具有多點(diǎn)刺激功能的鉑黑絲狀微電極，研究了絲電極的制備工藝。在電極制備過程中，采用生物相容性好的鉑作為電極材料，Parylene為封裝材料，使用lift-off工藝簡單有效地制備了多電極點(diǎn)絲電極。研究了通過電極表面修飾技術(shù)來優(yōu)化電極電化學(xué)性能。使用基于超聲輔助的電流脈沖電鍍鉑黑鍍層于電極點(diǎn)上，進(jìn)一步降低了電極阻抗，增加了電荷存儲(chǔ)容量，同時(shí)增加鍍層與基底結(jié)合力，提高了機(jī)械穩(wěn)定性。在超聲衰減測(cè)試中，相比傳統(tǒng)的直流電鍍的鉑黑電極，基于超聲輔助的脈沖電流電鍍的鉑黑電極陰極電荷注入容量的衰減量只有前者的三分之一。且經(jīng)過2.19×108個(gè)電脈沖老化后，其陰極電荷注入容量幾乎不變，顯示了較好的電化學(xué)穩(wěn)定性。并且在電極折彎實(shí)驗(yàn)中也顯示了較好的折彎穩(wěn)定性。研究了電極加速老化模型。在加速老化實(shí)驗(yàn)中，電極保持在87℃生理鹽水中8個(gè)月，與保持在人體內(nèi)環(huán)境下21年的時(shí)間相當(dāng)，其阻抗與陰極電荷注入容量在實(shí)驗(yàn)后期保持相對(duì)穩(wěn)定，顯示了電極長期植入后具有較好的穩(wěn)定性。并對(duì)鉑黑電極進(jìn)行了生物相容性實(shí)驗(yàn)。鉑黑電極植入兔肌肉中兩周后，其組織反映與鉑電極相同，顯示了其具有較好的生物相容性。 2、研究了一種基于Parylene的半球凸起微電極陣列。研究了三維凸起微電極陣列的制備工藝。在微電極陣列的制備過程中，使用了MEMS技術(shù)及光刻膠熱熔回流技術(shù)控制電極形貌。對(duì)模型進(jìn)行了相關(guān)的電學(xué)和力學(xué)仿真。為了改善其電化學(xué)性能，同樣在電極點(diǎn)上進(jìn)行了基于超聲輔助的脈沖電流電鍍鉑黑的方式來進(jìn)行電極表面修飾。并且對(duì)制備出的半球凸起電極進(jìn)行了阻抗測(cè)試，結(jié)果表明半球凸起電極較同底面積的平面電極有更小的阻抗。 3、研究了一種基于柔性MEMS技術(shù)的芯片電極多層互連技術(shù)。研究了芯片電極多層互連結(jié)構(gòu)的制備工藝。采用了基于PDMS為基底的芯片電極多層互連方法，系統(tǒng)集成度高，尺寸小。相比傳統(tǒng)的單層互連結(jié)構(gòu)，多層互連結(jié)構(gòu)單位面積上互連電極數(shù)量多，使用聚合物PDMS作為基底材料，節(jié)約工藝成本，絕緣層為絕緣性能良好的具有較好柔性Parylene薄膜，可使制備的互連結(jié)構(gòu)具有一定的柔性。 4、研究了基于透皮方式的體內(nèi)充電技術(shù)。分別設(shè)計(jì)并制備了基于單針和雙針插頭的植入式體內(nèi)供能裝置。在基于單針插頭的植入式體內(nèi)供能裝置的設(shè)計(jì)與制備中，使插座內(nèi)的雙層金屬網(wǎng)與針狀插頭形成過盈配合，實(shí)現(xiàn)了在整個(gè)金屬網(wǎng)區(qū)域均可給植入體內(nèi)的電池充電。在使用不同角度將插頭插入電池單元過程中，接觸電阻均小于1，顯示了較高的連接可靠性。且通過植入生物組織后，將針透過皮膚插入插座單元，能有效測(cè)量出電池電壓，顯示了操作的方便性。具備較好柔性的PDMS封裝外殼在插頭刺入多次后仍能保持其良好的防水性，以阻止體液的滲透給系統(tǒng)帶來損害。另外，較小的刺入力進(jìn)一步顯示了充電過程的方便性。在基于雙針插頭的植入式體內(nèi)供能裝置的設(shè)計(jì)與制備中，使插座內(nèi)的兩片金屬網(wǎng)位于同一平面上，并在充電時(shí)與雙針插頭同樣形成過盈配合，這樣可以減小器件厚度，且其同樣具備基于雙針插頭的植入式體內(nèi)供能裝置的特性。 5、研究了刺激與采集相關(guān)技術(shù)，主要包括實(shí)現(xiàn)刺激與采集功能的系統(tǒng)框架及其硬件電路的實(shí)現(xiàn)形式。進(jìn)行了肌電信號(hào)采集和肌肉刺激的動(dòng)物實(shí)驗(yàn)。在肌電信號(hào)采集的動(dòng)物實(shí)驗(yàn)中，使用了三組具有不同電極點(diǎn)面積的電極對(duì)同一只兔子的同一個(gè)眼輪匝肌位置分別進(jìn)行兔持續(xù)閉眼、持續(xù)眼以及誘發(fā)閉眼三種狀態(tài)下的肌電信號(hào)的采集。然后對(duì)每種狀態(tài)下的不同組電極采集到的信號(hào)進(jìn)行時(shí)域和頻域的分析比較，得出電極點(diǎn)面積較大的電極采集到的肌電信號(hào)的幅值和功率都較大。并且，利用一組采集電極從同一只兔子的同一眼輪匝肌位置上采集兔自然持續(xù)閉眼、自然持續(xù)睜眼、自然眨眼以及誘發(fā)閉眼四種狀態(tài)下的肌電信號(hào)。然后對(duì)信號(hào)進(jìn)行時(shí)域和頻域的信號(hào)處理，觀察不同兔眼動(dòng)作狀態(tài)下的肌電信號(hào)的區(qū)別和聯(lián)系，結(jié)果顯示，誘發(fā)閉眼的肌電信號(hào)的幅值和功率都較其它三種狀態(tài)大。在電刺激動(dòng)物實(shí)驗(yàn)中，使用電荷不平衡雙向電流脈沖分別對(duì)兔眼輪匝肌進(jìn)行了開環(huán)和閉環(huán)電刺激，達(dá)到了較好的效果。
[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.

【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R318.1;R651.3

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