近年來，以場效應電晶體（bio-FETs）為基礎的生物傳感器因其獨特的特性、高靈敏度、良好的選擇性以及易於應用於便攜式電子設備中而受到人們矚目及興趣。在本實驗中，我們設計並展示了一種利用 FET 即時檢測分子之間相互作用的方法。在此方法中，利用 FET 傳感器電訊號和光訊號高靈敏度的獨特功能。使用場效應電晶體來檢測與抗體和抗原分子結合前後，分子電荷和光子吸收的訊號變化。採用固定在 FET 表面的酵素免疫分析法(ELISA) 夾層結構來檢測嗜中性白血球明膠酶相關脂質運載蛋白(NGAL)。利用這種實驗技術，對NGAL靈敏度定量檢測，電訊號的檢測靈敏度達到0.1 pg/mL，氧化 TMB 光吸收檢測具有 < 1 pg/mL 的靈敏度。接著我們研究了矽奈米線場效應電晶體 (bio-NW FET) 的生物感測器作為分子光吸收感測器的潛力。以槲皮素和銅 (Cu2+) 離子為例，使用 opto-FET 方法檢測分子的相互作用，研究顯示波長為 450 nm 的光會被化合物所吸收，吸收量則取決於 Cu2+ 的濃度。對介於 0.1 μM 和 100 μM 之間的 Cu2+ 濃度進行化合物分子吸收的定量檢測，在優化後的系統電位參數下，分子對光的吸收量與銅離子濃度呈線性正比關係，結果顯示本研究使用的opto-FET 方法所檢測到的光吸收度不亞於市面上常見的紫外-可見光分光光度法，此外，我們證明此量測平台在生物傳感器的臨床應用中表現出色。

The biosensor based on field-effect transistors (bio-FETs) has have attracted great interest in recent years owing to their unique properties, high sensitivity, good selectivity, and easy integration into portable electronic devices. In this work, we propose and demonstrate a method that utilizes FETs for real-time detection of interactions between molecules. In this method, FET based sensors employ two unique functions, high charge sensitivity and high photon responsivity. We use the transistors to detect changes in molecular charge and photon absorption related with the binding of antibody and antigen molecules. We adopt an Enzyme-Linked Immunosorbent Assay (ELISA) sandwich structure immobilized on the FET surface to detect neutrophil gelatinase associated lipocalin (NGAL). Using this technique, we detect NGAL quantitatively with a sensitivity of 0.1 pg/mL and < 1 pg/mL based on charge sensing and oxidized TMB absorption detection, respectively.
Next, we explored the potential of applying biosensors based on silicon nanowire field-effect transistors (bio–NW FETs) as molecular absorption sensors. Using quercetin and Copper (Cu2+) ion as an example, we demonstrated the use of an opto–FET approach for the detection of molecular interactions. We found that photons with wavelengths of 450 nm were absorbed by the molecular complex, with the absorbance level depending on the Cu2+ concentration. Quantitative detection of the molecular absorption of metal complexes was performed for Cu2+ concentrations ranging between 0.1 μM and 100 μM, in which the photon response increased linearly with the copper concentration under optimized bias parameters. Our opto–FET approach showed a comparable absorbance with that of a commercial ultraviolet-visible spectrophotometry. Furthermore, we show that this platform performs great for diagnostic applications of biosensors.

摘要 i
Abstract ii
Acknowledgement iv
Table of Contents vi
List of Figures viii
List of Table xiii
Chapter 1 Introduction 1
Chapter 2 Background, Principles, and Concepts 4
2.1. Biosensor 4
2.2. Silicon Nanowire Field-Effect Transistor 5
2.2.1. Working Principle of Silicon Nanowire-based Device 7
2.2.2. Si-NW Bio-FET 9
2.2.3. Photosensitive Si-NW Bio-FET 13
2.3. Debye Length Screening 14
2.4. Surface Modification and Functionalization of Silicon Oxide 15
2.5. Enzyme-linked Immunosorbent Assay (ELISA) and NGAL 17
Chapter 3 Device Fabrication and Measurement Technique 21
3.1. Fabrication of Si-NW Bio-FET 21
3.2. Fluidic Channel 23
3.3. Measurement System 25
3.4. Procedure of Surface Modification and Functionalization of Silicon Oxide 27
3.5. Procedure of Molecular Charge Detection 29
3.6. Procedure of Molecular Absorption Detection 29
3.7. Materials 31
Chapter 4 Detection of Molecular Charge and Molecular Absorption 32
4.1. Absorption Spectra of HRP Redox Reaction with TMB 32
4.2. Device Characteristics of Si-NW Bio-FET 33
4.3. Photosensitive Si-NW Bio-FET 34
4.4. Surface Modification of Si-NW Bio-FET 37
4.5. Detection of Molecular Charge 40
4.6. Detection of Molecular Absorption 43
4.7. Detection of Quercetin - Cu2+ complexes using bio-FET as photodetector 45
Chapter 5 Conclusions 52
References 53
Appendix 60

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