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研究生:謝谷孟
研究生(外文):Ku-MengHsieh
論文名稱:應用環型指叉電極進行糖化血色素阻抗量測晶片之研究
論文名稱(外文):Glycated Hemoglobin Affinity Biosensors with Ring-Shaped Interdigital Electrodes on Impedance Measurement
指導教授:張凌昇
指導教授(外文):Ling-Sheng Jang
學位類別:碩士
校院名稱:國立成功大學
系所名稱:電機工程學系碩博士班
學門:工程學門
學類:電資工程學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:英文
論文頁數:53
中文關鍵詞:糖化血色素環型指叉式電極自組性單分子層硼酸親合力阻抗量測電容式生醫感測器
外文關鍵詞:Glycated hemoglobin (HbA1c)ring-shaped interdigital electrodes (RSIDEs)self-assembled monolayer (SAM)thiophene-3-boronic acid (T3BA) Boronic AffinityImpedance MeasurementCapacitor Biosensor
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隨著科技發展,糖尿病患者日益攀升,因此糖尿病的預防與控制成為一個急需關注的議題。許多研究提出,控制糖化血色素的濃度可以預防或延緩糖尿病併發症產生,其最大的優勢不同於一般血糖值,容易受到藥物、運動、飲食等因素影響,常有相當大的起伏而造成誤判,糖化血色素之濃度為紅血球生命周期內的平均血糖濃度,較為準確可靠。
目前糖化血色素的量測技術受到檢測儀器成本高、操作複雜、不易攜帶等限制,因此研發成本低、設備小、簡單快速、可攜式的感測晶片為重要的研究議題。本篇論文整合指叉式電極及雙螺旋式電極,並利用交流電滲流可驅動奈米粒子的特性,設計新式環型指叉電極來改善糖化血色素在感測電極上的分佈均勻度及固定效率,進而提升感測的靈敏度,並縮短檢測所需的時間。在電極上利用硫吩硼酸修飾表面形成自組性單分子層,由於硫吩硼酸會與糖類反應產生二醇亞硼酸使糖化血色素固定在電極表面,而生物分子吸附在電極表面時會造成阻抗的變化,最後藉由電極加以電訊號直接量測電極間的電容變化,並比較附著前與附著後的阻抗,不同濃度的糖化血色素會產生不同比例的阻抗變化,成功檢測出濃度區間1~100 ng/µL之糖化血色素,便以此畫出糖化血色素之檢量線。
Glycated hemoglobin (HbA1c) is one of the most important diagnostic assays for the long-term mark of glycaemic control in diabetes. This study presents an affinity biosensor for HbA1c detection based on impedance measurement, the detection process of which is label-free requiring no additional reagents, and features low cost and low sample volume. The ring-shaped interdigital electrodes (RSIDEs) are designed to promote the distribution uniformity and immobilization efficiency of HbA1c, and are further employed to characterize the impedance change and identify various concentrations of HbA1c. The self-assembled monolayer (SAM) of thiophene-3-boronic acid (T3BA) is provided to modify the gold electrode surface. Afterwards, the esterification reaction between HbA1c and T3BA produces a relative change of electrical property on the electrode surface. The RSIDEs with SAM of T3BA exhibits a wide range from 100 to 10 ng/µL producing an approximate logarithmic decrease of impedance, a low detection limit of 1 ng/µL, a good selectivity and short-term stability for HbA1c determination. The remarkable advantages, including miniaturization and low-cost, have the potential of point-care diagnostics for portable sensor development.
中文摘要 1
ABSTRACT 2
CONTENTS 4
LIST OF TABLES 6
LIST OF FIGURES 7
CHAPTER 1 INTRODUCTION 10
1.1 Background and Motivation 10
1.2 Electrode Design 12
1.2.1 Interdigital Electrode 12
1.2.2 Ring Structure 12
1.3 Affinity-based Impedance Biosensor 13
1.3.1 Surface Modification of Gold Electrode 13
1.3.2 Protein Immobilization 14
1.3.3 Detection Technology 15
1.4 Organization of the Dissertation 16
CHAPTER 2 ELECTRODE DESIGN 17
2.1 Structure Design 17
2.2 COMSOL Simulation 19
2.3 Electrode Parameters 22
CHAPTER 3 EXPERIMENTAL METHODS 23
3.1 Chip Fabrication and Materials 23
3.2 Electrode Modification 25
3.3 Experimental Condition Examination 26
3.3.1 Driving Signal of HbA1c 26
3.4 Impedance Measurement 28
CHAPTER 4 RESULTS AND DISCUSSION 31
4.1 HbA1c Driving Signal Examination 31
4.1.1 Fluorescence Labeling 31
4.2 Electrical Impedance Measurements 35
4.2.1 Distinguish Various Ion Concentrations of PBS 35
4.2.2 Detection of Various Concentrations of HbA1c 37
4.3 Electric Circuit Model 40
4.3.1 Electric Circuit Model before HbA1c Immobilization 40
4.3.2 Electric Circuit Model after HbA1c Immobilization 41
4.3.3 Electric Circuit Model Analysis 43
CHAPTER 5 CONCLUSION 47
REFERENCE 48
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