場效應電晶體使用不同閘極與聚乙二醇改質對於不同鹽濃度緩衝液影響pH量測之研究

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姓名

楊詠淇(Yong-Qi Yang) 查詢紙本館藏

畢業系所

化學工程與材料工程學系

論文名稱

場效應電晶體使用不同閘極與聚乙二醇改質對於不同鹽濃度緩衝液影響pH量測之研究
(The Comparisons of Voltage Shifts between Top-gate and Bottom-gate Nanowire FET on pH Sensing with Different Salt Concentrations and PEG Surface Modification)

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摘要(中)

矽奈米線場效應電晶體(silicon nanowire field effect transistor, SiNW FET)元件擁有即時檢測、高靈敏性、免標記等優勢，可用來檢測超低濃度帶電性的生物標誌物，作為生物感測器。FET量測操作上主要分成top-gate、bottom-gate和dual-gate三種施加閘極電壓的方式，基本上以top-gate和bottom-gate施加閘極電壓方式以獲取電子通道上的電流-電壓資訊（I-V curve）最為常見。
過去為了避免德拜長度（Debye-length）的干擾，不管使用哪種方式施加閘極電壓多數量測時會選擇使用低鹽濃度的緩衝溶液。然而考慮生物分子作用專一性與親和性等作用機制，生物標誌物與元件上的生物探針的最佳結合條件常常是在生理鹽濃度(150 mM)，所以在低鹽環境下生物標誌物與探針的結合能力會降低，進而影響檢測結果的準確性以及醫學檢驗的應用性。
所以為了系統性地探討以不同方式施加閘極電壓在不同鹽濃度的I-V曲線，本研究藉由在不同鹽濃度下量測不同pH值緩衝液的檢測的方式來分析不同閘極電壓施加位置的I-V curve與pH檢測的關係，以建立基礎生物感測器的系統量測資訊。
另外，為了避免生物感測器表面之抗非特異性吸附，及了解離子在FET表面上游離對I-V訊號的穩定度影響，本研究也選擇強水合能力、具生物相容性的聚乙二醇(Polyethylene glycol, PEG)，探討PEG/FET表面對於不同鹽濃度、pH、及不同閘極操作的影響。最後，本研究同時也嘗試探討不同大小的鹽離子(Bis-Tris Propane, BTP及Phosphate buffer saline, PBS)作為緩衝溶液觀察對pH檢測的解析度。
本實驗選擇相同的SiNW FET元件設計，只有在不同閘極之電極使用方法上不同，並且在bottom-gate元件的奈米線背部有另外打線連接閘極。
以10 mM BTP做為檢測溶液從pH 2到pH 11檢測實驗結果發現top-gate和bottom-gate FET在相同鹽濃度量測下的整體斜率變化相差不大，可見兩者對於pH改變的敏感性差不多。接著探討鹽濃度的改變，發現對於表面未改質的top-gate FET的檢測都比bottom-gate FET在pH量測上電訊號變化有比較穩定。相同條件下top-gate FET在不同元件量測到的電訊號標準差可以在10 mV以內，斜率也可以達到57 mV/pH。氧化物表面修飾上PEG之後，更可以明顯的發現在高鹽濃度時標準差會下降，但是bottom-gate則無論表面是否有做PEG修飾訊號都還是不太穩定，當嘗試更低鹽濃度1 mM和0.1 mM BTP檢測後，發現訊號雖會有稍微穩定的現象，但標準差仍超過30 mV。因為top-gate FET對鹽濃度幾乎不受影響。改質PEG後可改善高鹽環境下因離子游離狀態較複雜使得背景雜訊較高的問題，所以後續實驗以top-gate FET為主。鹽離子種類實驗結果比較(BTP Vs. PBS)，PBS的解析度較低推論是因為溶液中帶正電的Na+比BTP分子小，有更強的能力可以進入表面做為反離子影響電訊號值。從本研究實驗結果得知pH值的改變是主要影響訊號的關鍵因素，其次是反離子的大小。
根據pH檢測結果，得知在基本電性量測上top-gate FET電訊號變化的穩定性比bottom-gate還要高，並且在表面修飾PEG可以達到抗離子貼附的作用。除了論文本體的pH sensing量測之外，也有利用top-gate FET表面做抗體探針固定化實驗，利用不同鹽濃度的檢測溶液希望找到最佳化固定條件。未來則是希望透過了解生物分子間結合條件使用top-gate FET作為生物感測器並利用scFv或其他抗體片段，找到最佳探針固定化條件、檢測環境。

摘要(英)

The silicon nanowire field-effect transistor (SiNW FET) has the advantages of ultrasensitive, label-free detection, and real-time detection. It can be used as a biosensor to detect ultra-low concentrations of biomarkers. The voltage-current information from electron channels can be designated in the top-gate and the bottom-gate FET systems. Users usually use a low sensing buffer′s salt concentration in either gate system to avoid the Debye length limitation.
To systematically investigate the impact of different salt concentrations of the sensing buffer on the top-gate and the bottom-gate FET, we analyze the voltage-current signal of sensing different pH values at different salt concentration buffers. We also modified the surface with high hydrophilicity polyethylene glycol (PEG), a common anti-fouling material used in biosensors. We then investigated the relationship between PEG/FET and gate voltage applied in different directions through pH sensing under different salt (Bis-tris propane (BTP) and phosphate-buffered saline (PBS)) concentrations. This study also discussed the effects of the size of the different ions investigated on the counter-ion distribution and the resulting FET I-V curve.
First, I tried to detect pH sensing from pH 2 to pH 11 to know the basic sensitivity of the top-gate and bottom-gate FET. According to the results, we know the sensitivity of these two is almost the same. Next step, I started to try the different salt concentrations. I found that the top-gate FETs were much more stable than the bottom-gate FETs, and the absolute values of standard deviations of every device of the top-gate FETs were lower than 10 mV, and the resolution is around 57 mV/pH. PEG/FET could make the lower disturbing signals of the bottom-gate FETs, and we can identify the lower salt concentrations of the buffer. However, the standard deviations of the bottom-gate FET were even higher than 30 mV, which reveals that the bottom-gate FET is hard to be used as an ultra-sensitive biosensor. Results of the comparison of BTP and PBS showed that the resolution of PBS is lower than the BTP buffer, and we thought that is due to the different sizes of counter-ions. We can conclude that the signals of top–gate FET with PEG are not affected much by the sensing buffer′s high salt concentration.
According to the pH sensing measurements, it was found that the stability of the electrical signal variation in the top-gate FET is higher than that in the bottom-gate FET for basic electrical measurements. Additionally, surface modification with PEG has been shown that can avoid ion adsorption. In addition to pH sensing measurements discussed in the paper, experiments were also conducted to immobilize antibody probes on the surface of the top-gate FET. Different salt concentrations as the sensing buffers were used to identify the optimal conditions for immobilization. In the future, the aim is to utilize the top-gate FET as a biosensor by understanding the binding conditions between biomolecules and utilizing scFv or other antibody fragments. The goal is to find the optimal probe immobilization conditions and detection environments.

關鍵字(中)

★ 場效應電晶體
★ pH 量測
★ 不同鹽濃度緩衝液影響
★ 矽奈米線
★ 聚乙二醇表面改質

關鍵字(英)

★ FET
★ pH sensing
★ Top-gate FET
★ Bottom-gate FET
★ PEG modification

論文目次

中文摘要 I
Abstract IV
誌謝 VI
目錄 VIII
圖目錄 XI
表目錄 XV
第一章緒論 1
第二章文獻回顧 3
2.1 抗體分子 3
2.1.1 抗體分子概論 3
2.1.2 抗體結構介紹 4
2.2 矽奈米線場效應電晶體 6
2.2.1 不同閘極電壓施加方式 7
2.2.2 將矽奈米線場效應電晶體作為pH感測器 9
2.2.3 將矽奈米線場效應電晶體作為生物感測器 15
2.3 緩衝溶液pH值與鹽濃度 21
2.3.1 Nernst equation與pH值的關係 21
2.3.2 鹽離子濃度與Debye length的關係 22
2.3.3 反離子對於訊號檢測的影響 25
2.4 晶片表面抗汙能力 27
2.4.1聚乙二醇的介紹及抗沾附特性 28
2.5 晶片表面改質 34
2.5.1 自組裝單層膜 34
2.5.2 表面分子固定化 38
第三章實驗藥品、儀器設備與方法 41
3.1 實驗藥品 41
3.2 實驗儀器 43
3.3 實驗方法 44
3.3.1 晶片表面清洗 44
3.3.2 不同鹽濃度、pH值緩衝液的配置 45
3.3.3 pH值電訊號量測 45
3.3.4 晶片表面改質與生物探針固定化 46
3.3.5 目標物電訊號檢測 48
3.3.6 矽控片改質 49
3.3.7 實驗數據分析方法 50
第四章結果與討論 52
4.1分析大範圍pH值量測的線性關係 52
4.1.1 Top-gate FET系統 52
4.1.2 Bottom-gate FET系統 57
4.2 使用不同鹽濃度緩衝液做pH檢測的比較 60
4.2.1 Top-gate FET 系統 60
4.2.2 Bottom-gate FET 系統 64
4.3 cTnI 生物檢測 66
4.2.2 XPS表面元素分析 66
4.2.1 利用抗體探針在不同鹽濃度檢測溶液下檢測 70
第五章結論與未來展望 73
5.1 結論 73
5.2 未來展望 75
第六章參考資料 76
第七章補充資料 82
7.1 Fermentation - scFv/BL21DE3 82
7.2 不同鹽濃度PBS緩衝液檢測結果 87

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指導教授

陳文逸(Wen-Yih Chen)

審核日期

2023-7-20

推文