近年來，心血管疾病已經成為造成死因的全球主要疾病之一，為了要降低心血管疾病的死亡率，如何有效預防心血管疾病成為了重要關注的議題，然而目前偵測心血管疾病的儀器通常太過於昂貴或者笨重，醫療費用之龐大對於一般民眾而言難以做到長期檢測，並且現今系統也缺乏可以提供定點照護的可行性。
隨著現今的報告研究表明，根據長期追蹤後發現一些生物指標可以成為評估心血管疾病風險的依據，當這些生物指標超過閥值時容易在近十年罹患心血管疾病。因此在這篇論文中主要提及如何實現可偵測這些生物性指標並且達到定點照護功能的雛型開發，雛型系統部分包括幾種主要功能：生物電晶體感測器(Bio-FET sensor)、微流體系統(The Microfluidic system)、溫度控制元件(TE-Cooler)，利用這些主要功能整合成一個定點照護系統的雛型。
系統主要透過微控制器MSP430F5438A以及周邊電路設計，例如：訊號讀出電路、微流體控制電路以及溫度控制電路來與各系統整合。微控制器透過控制電路控制微流體系統與溫度控制元件對生物指標進行處理後，再透過讀出電路配合微控制器積分生物電晶體上的電荷量變化，進而顯示檢測的生物指標濃度。
經過我們有效的電路設計，目前完成的雛型大小為55公分x24公分x22公分，內部使用電源是常規5伏特，易於之後可以擴充其他功能元件。目前量測以C型反應球蛋白(C-reactive protein, CRP)為樣本，系統偵測極限可辨識濃度為每公升0.1毫克，相較於傳統偵測方式極限在每公升5毫克來的準確。並且偵測時間在5分鐘以內已可達到快速篩檢的要求。溫度控制可穩定在正負攝氏1度，並且升溫率可達每秒攝氏4度已符合現今生物實驗溫度系統上的要求。以上規格及效能已經顯示出本系統雛型擁有擔任心血管疾病風險評估以及定點照護儀器的可行性。

Cardiovascular disease (CVD) has ranked as one of the most notorious cause to death today. As the result, how to prevent the CVD has become an important issue. However, available devices detecting the CVD are too expensive and bulky nowadays. In other words, people can not use these devices to do the long-term monitoring. Furthermore, these devices can not provide the point-of-care applications.
Recent researches on biomarkers exhibit great potentials to detect CVD. The biomarker concentration in the blood can be evidence of CVD risk. To be more specific, if the concentrationof the biomarkers in the blood is over the threshold, the possibility of suffering CVD
will be increased in the next decade. Hence, in this thesis, we build up an electronic system to integrate the sensors, microfluidic system, and temperature control unit in a prototype system.
To build down the system, the core engine is a micro-controller MSP430F5438A and peripheral circuits are readout circuits, temperature control circuits, and the microfluidic system control circuits. In the meanwhile, the controller will synthesize all the signals to control the microfluidic system, and the temperature control unit for the biomarker incubation. In addition, the controller will calculate the integrated output charges of the field-effect transistor (FET) biosensor with its gate-to-output transconductance depending on the biomarker concentration. Finally, the LCD display shows the concentration of biomarkers. The dimension of the system is 55 cm x 24 cm x 22 cm. Internal supply voltage is 5 V, easily to be integrated with other electronic components. By using C-reactive protein (CRP) as the test biomarker, the detectable concentration can be 0.1mg/L. This resolution is more accurate than conventional method which is 5 mg/L. The detection time is 5 minutes. The accuracy of the temperature control can be within 1 °C and ramp rate is 4 °C/s. The performance demonstrates its feasibility for evaluating the risk of CVD and point-of-care applications.

1 Introduction 1
1.1 Background . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Motivation . . . . . . . . . . . . . . . . . . . . . 3
1.3 Organization . . . . . . . . . . . . . . . . . . . . 3
2 Detection of CVD Biomarkers for Point-of-Care Applications 5
2.1 Overview . . . . . . . . . . . . . . . . . . . . . . . 5
2.2 The Microfluidic Technology . . . . . . . . . . . . . . .6
2.2.1 Processing Steps for Biomarkers . . . . . . . . . . . .7
2.2.2 Microfluidic Chip . . . . . . . . . . . . . . . . . . .8
2.3 Bio-FET Detection . . . . . . . . . . . . . . . . . . . .11
2.3.1 Typical Detection Methods . . . . . . . . . . . . . . .11
2.3.2 Bio-FET Detection Method . . . . . . . . . . . . . . . 11
3 The Proposed Point-of-Care CVD Detection System 15
3.1 Microfluidic System . . . . . . . . . . . . . . . . . . .16
3.1.1 Microfluidic Control Circuits . . . . . . . . . . . . .16
3.1.2 Temperature Control Circuits . . . . . . . . . . . . . 22
3.2 Bio-FET Control and Readout . . . . . . . . . . . . . . .27
3.2.1 Peripheral Circuits . . . . . . . . . . . . . . . . . .28
3.2.2 Verification . . . . . . . . . . . . . . . . . . . . . 29
3.3 System Controller . . . . . . . . . . . . . . . . . . . .33
3.3.1 Embedded System Platform . . . . . . . . . . . . . . . 33
3.3.2 Firmware Design . . . . . . . . . . . . . . . . . . . .34
3.4 User interface . . . . . . . . . . . . . . . . . . . . . 38
4 Implementation 39
4.1 Experimental Setup . . . . . . . . . . . . . . . . . . . 39
4.2 Verification of the Microfluidic System . . . . . . . . .39
4.2.1 Pressure Verification . . . . . . . . . . . . . . . . .40
4.2.2 Flow of Microfluidic Chip . . . . . . . . . . . . . . .41
4.3 Stability of Temperature System . . . . . . . . . . . . .42
4.4 Verification of Detection System . . . . . . . . . . . . 44
4.5 Prototype Implementation . . . . . . . . . . . . . . . . 46
5 Conclusions and Future Works 49
5.1 Conclusions . . . . . . . . . . . . . . . . . . . . . . .49
5.2 Future Works . . . . . . . . . . . . . . . . . . . . . . 50

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