微電極核酸電晶片生物感測器

Abstract

核酸電化學生物感測器利用合成核酸適體檢測目標分子是否存在與其濃度，提供即時檢測，無須額外試劑。本篇論文旨在發展微電極晶片生物感測器，將此核酸電化學反應的優勢進一步擴大，以做到隨身且即時的藥物濃度檢測。論文中提出一種嶄新的方法，使用計時安培法搭配取樣電路在兩個電壓間循環跳動，可以將每次量測所需的時間減少10倍以上，進一步大量減少功耗。除此之外，基於FET電壓緩衝訊號讀出電路的架構，更是可以將輸入參考電流噪聲降低千倍，來應對在晶片微電極上所需要之極大的動態範圍。 本篇論文花費了大量時間使用卡那黴素與氨芐西林適體測試晶片上微電極的抗壓性，使用了電子束蒸鍍金鹽與無電鍍鎳浸金來製造微電極，針對電極的抗腐蝕、導電性、與適體的黏著力還有持久力，做了許多測試，望能找出一個最佳的後製程方法來製造晶片。結果顯示在底材為鋁的電極上進行電化學反應將會遇到極大的困難，難以克服良率與持久性的問題。 在電路上則成功驗證了FET做為電壓緩衝的可行性，在使用三種濃度(0.1 毫莫耳, 1 毫莫耳, 10毫莫耳)的亞甲藍液的測試下，成功觀察到氧化還原反應造成電子動力學的改變，對於下一版本是勢在必行。

The nucleic acid electrochemical biosensor utilizes synthetic nucleic acid aptamers to detect the presence and concentration of target molecules, providing real-time detection without the need for additional reagents. This thesis aims to develop a small on-chip electrode biosensor to further expand the advantages of this nucleic acid electrochemical reaction, achieving portable and real-time drug concentration detection. A novel approach is proposed in this thesis, using chronoamperometry combined with sample and hold circuit to cyclically jump between two voltages, reducing the time required for each measurement by more than tenfold and significantly reducing power consumption. Furthermore, based on the structure of the FET voltage-buffered signal readout circuit, input refer current noise can be reduced by a factor of a thousand to address the substantial dynamic range required for on-chip microelectrodes. Considerable effort has been devoted to testing the resistance of on-chip electrodes to kanamycin and ampicillin aptamers, using e-beam evaporated gold and electroless nickel immersion gold plating to manufacture the microelectrodes. Various tests have been conducted to assess the electrode''s resistance to corrosion, conductivity, aptamer adhesion, and durability, aiming to identify the optimal post-processing method for chip fabrication. The results indicate significant challenges in conducting electrochemical reactions on electrodes with aluminum substrates, making it difficult to overcome issues related to yield and durability. On the circuit side, the feasibility of using FET as a voltage buffer has been successfully validated. Testing with three concentrations (0.1 mM, 1 mM, 10 mM) of methylene blue solution has successfully observed changes in electron kinetics caused by oxidation-reduction reactions, making it imperative for the next version.