臺灣博碩士論文加值系統

針對單一細胞做分析比採取一群細胞做分析提供了更精確及更深入的資訊對於生物細胞體研究方面，且由於MEMS技術的成熟，使得微流體裝置能夠輕易的製作並且達到單一細胞研究的等級(奈米)。電阻抗量測為現今對單細胞研究最有效的一種方法。量測單細胞阻抗時，電極形狀和細胞位置的關係會影響量測的精確性。有鑑於此，本論文採取數值模擬的方法並搭配實驗的分析去研究這兩項因素對於單細胞阻抗量測的影響。
本研究設計了四種不同形狀的電極：平行電極、橢圓電極、船板電極、和花狀電極。使用數值模擬分析不同細胞位置坐落於這些電極所產生的影響，並藉由探討電阻抗值的變化、靈敏度高低及感測區域的大小，進而界定出最佳的量測電極去設計單細胞阻抗量測的微流體裝置。　　
　　實驗方面，選取模擬結果較佳的兩種電極－平行電極和橢圓電極。實驗裝置包括捕捉細胞的機制和量測的電極，並針對不同細胞的位置作阻抗量測。實驗結果証明了細胞阻抗值與細胞和電極重疊面積大小呈反比的現象。並且根據本研究所推論出的公式，在不同細胞位置所量測的細胞阻抗值可以修正為一致。

Measurements on single cells provide more accurate and in-depth information about electrical properties than those on pathological tissues. The relationship between electrode geometry and the location of a cell on microfluidic devices greatly affects the accuracy of single cell impedance measurement. Accordingly, this study presents numerical solutions from the FEM simulation of the COMSOL multiphysics package and experimental measurements to analyze the effects of electrode geometry and cell location on microfluidic devices. An equivalent electrical circuit model is developed to obtain the impedance and sensitivity of various cell locations on various electrode geometries using FEM simulation. According to the simulation results, the parallel electrodes have the largest sensing area (39μm2) and the highest sensitivity (0.976) at a voltage of 0.1 V and a frequency of 100 kHz. Increasing the width of electrodes provides a large sensing area but reduces sensitivity, whereas decreasing the gap between electrodes increases both sensing area and sensitivity. In experiments, the results demonstrate that the magnitude is inversely proportional to the overlap area of the cell and electrodes. Moreover, the impedance of single HeLa cells measured at various cell locations can be modified using equations determined from the modeling and experimental results.

中文摘要 I
ABSTRACT II
ACKNOWLEDGEMENT III
CONTENT IV
LIST OF TABLES V
LIST OF FIGURES VI
CHAPTER 1 INTRODUCTION 1
1.1 Background 1
1.2 Single-cell-analysis 1
1.3 Paper review 2
1.4 Motivation 7
1.5 Advantages of this work 8
CHAPTER 2 SIMULATION 10
2.1 Simulation setup 10
2.1.1 COMSOL Multiphysics package 10
2.1.2 Four kinds of electrodes 10
2.2 Proof of the simulation 12
2.3 Electric fields for four kinds of electrodes 14
CHAPTER 3 Electrical modeling of single cell analysis system 16
CHAPTER 4 FABRICATIONS AND EXPERIMENT SET UP 18
4.1 Chip Fabrication 18
4.1.1 Mask Design 18
4.1.2 Fabrication Process 19
4.2 Experimental setup 21
4.2.1 Measurement device 21
4.2.2 Measurement Instrument 21
CHAPTER 5 RESULTS AND DISCUSSIONS 24
5.1 Simulation results of single cell analysis 24
5.1.1 Electric field distributions 24
5.1.2 Impedance variation and sensing area 26
5.1.3 Sensitivity 32
5.2 Experimental results of impedance measurement for single HeLa cells 35
CHAPTER 6 CONCLUSIONS 42
References 44

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