以高密度微電極陣列軟性電路元件進行視網膜神經網路的電性感受區之研究

The electrical receptive field of retinal neural network with high-density MEA Flex

王富民(Wang, Fu Ming)

指導教授 ： 范龍生

國立清華大學/工學院/奈米工程與微系統研究所/碩士(2015年)

摘要

老年黃斑病症、視網膜色素變性是常見於眼球疾病，進而造成病患失明。為了幫助此類病患，許多的團隊投入視網膜修復的研究，希望能夠成功使病患重建視覺的能力。利用微電極陣列軟性電路元件，透過電刺激訊號與視網膜神經細胞的交互作用，產生訊號的產生、傳遞以及細胞間彼此交互作用，最後讓病人重見光明。雖然目前已經有成功商品化的產品幫助許多的病患重見光明，但是在不同病患上所得到的結果差異性相當大且要達到法定眼盲視力0.1(20/200)，仍然有相當大的空間需要繼續改善。
所存在的主要瓶頸是，目前對於訊號在視網膜神經網路的編碼尚未完全明瞭，視覺的解析度、色彩的產生方式也不甚了解，而且電訊號是否能完全取代光訊號仍有待考證。目前所知神經網路的編碼與細胞的感受區有關，但目前實驗的方式都無法給予圖形化的電刺激與記錄整體節細胞的反應；因此，設計MTM系統平台用於研究視網膜神經細胞的電性感受區，了解神經網路的編碼，以求未來給予電刺激訊號能達到最佳效果。
論文中以Patch Clamp進行視網膜體外實驗，驗證自行開發的高密度微電極陣列軟性電路元件的下視網膜電刺激能力，所需最低的有效電刺激強度為1.44mC/cm2；而開發的MTM研究平台，具備多電極刺激與多電極記錄的能力。將所記錄到的訊號經過數據處理後，以Threshold V的方式尋找細胞訊號，初步的結果可以量測到細胞的訊號約在30~40uV。再將所有的細胞訊號重疊後取平均值，將雜訊降低後所得到的特徵波形斜率為0.13uV/us。

關鍵字

視網膜 ； 微陣列電極 ； 軟性電路板 ； 電刺激 ； 視覺重建 ； MTM

並列摘要

Age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are common diseases in eyes. They can make the patients blind when they become severe. Nowadays, a lot of research groups are devoted to retinal prosthesis, the goal is to help patients rebuild their visual ability. By interaction between retinal neurons and electro-stimulations which are released by microelectrode array, the artificial visual signals can be created, transmission and then let the patients have visual ability again. Although, there is a commercial product in the market, the weakness is that rebuilding visual acuity cannot reach 20/200 (less than 20/200 means the blindness) and the recovery effects are different from people to people. So it means that this product still has a huge space can be improved.
The bottle neck is that the signal transmission in the retinal network is not completely clear and the production of color and visual acuity still remains a big issue. Whether the artificial electrical signal can totally replace the normal signal in the retina? The research has proved that the retinal neural network is related to the retinal receptive field, it is hard to give pattern stimulation and record all the reactions of retinal ganglion cells at the same time. Therefore, in this research, MTM system is created to solve the problems above and finds out the best way to give the stimulation effectively.
In this research, patch clamp is used to do the retinal experiment in vivo and prove that the MEA flex made by our lab can do the sub-retinal stimulation. The lowest effective stimulation is 1.44mC/cm2. The MTM system is equipped with multi-electrode stimulation and multi-electrode recording. The data are processed by the data analysis and search the cell signals by threshold voltage. The primary experiment is that MTM system can detect the cell signal about 30~40V. After averaging all the cell signals and reduce the noise, the slope feature of the cell signal wave is 0.13V/s.

並列關鍵字

Retina ； microelectrode array ； electro-stimulation ； retinal prosthesis ； MTM

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