長庚醫學團隊發現了三種與帕金森氏症相關的三種蛋白，利用這幾種蛋白可以做為判斷是否患上帕金森氏症的重要依據，目前臨床上判斷帕金森氏症是利用UPDRS(The unified Parkinson's disease rating scale)來做為判斷的依據，此量表針對心理狀態、行為和情緒等……作為評分的依據，由於此量表需要從各方面做判斷，因此需要有經驗的醫生做為強力的後盾，這也代表在分數評估上沒有辦法做到完全客觀的判斷，因此計畫提供了物理及化學的方式以提供一個主觀且準確的判斷依據，而化學的部分有兩種方式，第一種是透過ISFET(ion-sensitive field-effect transistor)來做為感測電路，另一種是使用ELISA(enzyme-linked immunosorbent assay)的呈色作為判斷依據。
ISFET在感測精準度尚有問題需要克服，元件的製程偏異、雜訊的干擾、抗體抗原是否成功接上等等的原因都可能造成判讀的問題，最大的問題在於穩定度不足，導致不同濃度下所量出數據的標準差有所交疊，這樣的資料無法作為判斷的基準，因此需數位電路作為輔助，本顆數位晶片的主要功能在於篩選ISFET矩陣內的有效資料，ISFET矩陣內含有大量數據，但不是每一個子元件內的數據都是有效的，透過濃度以及數值的變化作為判斷的依據來篩選出有效的資料，由於ISFET晶片仍會做改版，此顆晶片提供四種模式做切換，以符合後續的各種不同設計，目前的設計總共使用五個濃度，經分析後發現抓取率過高或過低的表現都不好，抓取率約莫在40%到50%有較好的表現，目前IS_2片的篩選處理上可以將原始的標準差降至5%左右，如此可以做出一條標準濃度下的標準曲線，後續病人檢體經量測並篩選所得出的數據就能回推當前濃度，作為帕金森氏症病期的客觀指標。
ELISA的呈色時間目前仍難以掌握，感光元件將呈色資料讀取後，使用數位晶片分析找出呈色反應是否飽和，已知濃度的抗原完成呈色反應後，其讀取到的資料繪製成標準曲線，未知濃度的抗原使用透過一樣的流程找出呈色飽和下的數值，再利用標準曲線即可回推當前的濃度，也可提供一套客觀的判斷標準。

Chang Gung Medical team discovered three kinds of three proteins related to Parkinson's disease. Using these proteins can be used as an important basis for judging whether you have Parkinson's disease. At present, it is clinically judged that Parkinson's disease is based on UPDRS. This scale is for psychological status, behavior, emotions, etc... as a basis for scoring. Because this scale needs to be judged from all aspects. Therefore, an experienced doctor is required to be a strong backing. This also means that there is no way to make a completely objective judgment on the score. This project provides physical and chemical methods to provide a subjective and accurate basis for judgment. There are two ways to do the chemical part. The first is to use an ISFET as the sensing circuit. The other way is based on the coloration of enzyme-binding immunosorbent assay (ELISA).
ISFET has problems in sensing accuracy and needs to be overcome. Process variation of components, noise interference and whether the antigen is successfully connected, etc. All these reasons may cause problems in interpretation. The biggest problem is the lack of stability. The standard deviation of the data measured at different concentrations overlaps. Such information cannot be used as a benchmark for judgment. Therefore, digital circuits are required as an aid. The main function of the digital chip is to screen the valid data in the ISFET array. ISFET array contains a lot of data. But not every cell’s data is valid. Screening out valid data by using changes in concentration and values as a basis for judgment. Since the ISFET chip will still be revised continuously. This chip provides four modes to switch. In order to meet the different designs of the follow-up. The current design uses a total of five concentrations. After analysis, it is found that the performance of the grab rate is too high or too low, and the grab rate is about 40% to 50%. The performance of the current IS_2 film screening process can reduce the original standard deviation to about 5% . This makes it possible to make a standard curve at a standard concentration. Patient samples can be measured and screened to obtain the current concentration. As an objective indicator of Parkinson's disease.
The coloration time of ELISA is still difficult to master. After the image sensor reads the color data, and use digital circuit to find out if the color reaction is saturated. The data read by the known concentration of antigen after the color reaction is drawn into a standard curve. The unknown concentration of antigen is used to find the value under color saturation through the same process. Then we can use the standard curve to push back the current concentration. This way can provide a set of objective criteria also.

中文摘要 -----------------------------------------i
Abstract --------------------------------------iii
目錄 --------------------------------------------v
圖目錄 -----------------------------------------vii
表目錄 ------------------------------------------x
第一章 緒論 ---------------------------------1
1.1 研究背景 ---------------------------------1
1.2 研究動機 ---------------------------------1
第二章 帕金森氏症 -------------------------3
2.1 帕金森氏症簡介 -------------------------3
2.1.1 簡介 ---------------------------------3
2.1.2 病症 ---------------------------------3
2.1.3 治療 ---------------------------------4
2.2 葉氏分級表(Hoehn and Yahr scale) ---------4
2.3 帕金森氏症評分量表(UPDRS) -----------------5
2.4 量表問題及解決方法 -----------------5
第三章 帕金森氏症檢測方法 -----------------7
3.1 電訊號 ---------------------------------7
3.1.1 離子感測電晶體(ISFET) -----------------7
3.1.2 抗原抗體濃度檢測 ------------------------12
3.1.3 雙閘式離子感測電晶體(Dual-gate ISFET) 15
3.1.4 離子感測電晶體資料結構 ----------------16
3.2 光訊號 --------------------------------18
3.2.1 酵素結合免疫吸附分析法(ELISA) --------18
3.2.2 成色問題 --------------------------------20
3.3 目標 --------------------------------22
第四章 電路實現與設計 ------------------------23
4.1 電訊號處理 ------------------------23
4.1.1 資料篩選原理 ------------------------23
4.1.2 篩選後資料分析 ------------------------29
4.1.3 篩選電路設計 ------------------------37
4.1.4 臨床應用 --------------------------------43
4.2 光訊號處理 ------------------------44
4.2.1 成色判斷電路設計 ------------------------44
4.3 晶片佈局 --------------------------------48
4.4 量測結果 --------------------------------49
第五章 結論與未來展望 ------------------------56
5.1 結論 --------------------------------56
5.2 未來展望 --------------------------------57
第六章 參考文獻 --------------------------------58

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