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標題: | 互補式金屬氧化物半導體生物感測晶片於定點照護檢測應用之研究 A Study of CMOS Biosensor Chip in Point of Care Testing Application |
作者: | I-Shun Wang 王義舜 |
指導教授: | 林致廷 |
關鍵字: | CMOS多晶矽奈米線,生物分子感測元件,心血管疾病,糖尿病,可靠度,POCT, CMOS poly-silicon nanowire,biosensor,cardiovascular diseases,diabetes,reliability,POCT, |
出版年 : | 2018 |
學位: | 博士 |
摘要: | 隨著人口爆炸性的成長,各種疾病正威脅著人類的生命和財產,如登革熱、糖尿病與心血管疾病等。而為了充分地利用有限醫療之資源,有效率地做出醫療分級與對於病情做出最有效之監控與快速篩檢,個人醫療診斷平台與定點照護檢測之開發受到相當程度之重視。藉由成熟的半導體技術產業,發展CMOS個人醫療體外定點照護診斷系統為近來主要研究發展之方向。
本論文利用台積電 0.35 μm 製程製作感測晶片。除了可針對急性心肌梗塞,檢測心臟衰竭指標蛋白和介白素6之心血管疾病之生物標的物做檢測,而在緩衝溶液中此晶片在介白素6 (IL-6)、心肌鈣蛋白(cTnI)和N端前腦利鈉肽(NT-proBNP)的檢測限分別確定為45 pM,32 pM和32 pM。此外,在臨床血清的量測下,開發的CMOS生物傳感器與從醫院中央實驗室獲得的酶聯免疫吸附測定(ELISA)具有良好的相關性。我們還在臨床血液樣本檢測中量測了血紅蛋白(Hb)和糖化血紅蛋白(HbA1c)。在日常血糖水平波動的情況下,HbA1c檢查是長期糖尿病監測中更好的方法。目前,HbA1c測試需要在實驗室或醫院進行,因為操作複雜,需要訓練有素的操作人員。這限制了它在家庭護理應用和資源有限的領域的應用。將感測結果與標準Hb和HbA1c測量方法進行比較並顯示可比較的結果。 最後,我們提出新型後端蝕刻設計以有效地減少晶片之間的誤差值,並良好控制奈米線上方氧化介電層的厚度。並用心肌鈣蛋白去驗證新型後端蝕刻設計,能有效降低量測變異率,提升感測器之可靠度,搭配半導體製程之技術可以很容易地與不同的功能模組做整合,例如無線網路和微流道系統。因此,本研究驗證了一個基於商用CMOS製程技術的生物傳感器平台的良好潛力,將可滿足對早期診斷和即時檢測系統(POCT)的需求。 Aging problems have become life threatens in modern societies. For instance, people are suffered from different kinds of aging diseases, such as cardiovascular diseases and diabetes. To effectively diagnose these diseases, in general, biomolecular marker analysis is one of the most important methods. However, traditional biomolecular analysis methods are human-intensive and time-consuming. To address these problems, in this work, a CMOS-based field-effect biomolecular sensing technology is developed and evaluated. The CMOS biosensor is implemented via a standard commercialized 0.35 μm CMOS process. Therefore, the developed technology has potentials for further translation into applications. The developed CMOS-based field-effect biomolecular sensing technology is aiming at two diseases, i.e. cardiac biomarkers (cardiac-specific troponin-I (cTnI), N-terminal prohormone brain natriuretic peptide (NT-proBNP), and interleukin-6 (IL-6)) and diabetes biomarkers (hemoglobin (Hb) and glycated hemoglobin (HbA1c)). To validate the developed technology, clinical sample were used and enzyme-linked immuno-sorbent assay (ELISA) was employed to examine the output of the proposed semiconductor sensors. To improve the sensitivity and uniformity of the developed technologies, furthermore, a lift-off post-end fabrication process was also proposed for 0.35 μm 2P4M commercially-available CMOS biosensor. To examine the proposed post-process, pH tests and cTnI measurements were utilized. As a consequence, the developed devices can be easily integrated into available electrical modules, such as wireless and microfluidic systems. And this work presents a CMOS based biosensor platform to accomplish the need of early diagnosis and point-of-care testing (POCT) system. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70335 |
DOI: | 10.6342/NTU201802134 |
全文授權: | 有償授權 |
顯示於系所單位: | 電子工程學研究所 |
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