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標題: | CMOS-BioMEMS壓阻式橋狀薄膜生物感測器於
癲癇小分子藥物苯妥英偵測之研究 A Study of CMOS-BioMEMS Based Membrane-Bridge Sensor on the Detection of Phenytoin |
作者: | Chao-Yuan Chiu 丘朝元 |
指導教授: | 顏毅廣(Yi-Kuang Yen) |
共同指導教授: | 張培仁(Pei-Zen Chang) |
關鍵字: | 橋狀薄膜,小分子量測,苯妥英,藥物治療監測,專一性鍵結, Membrane-bridge,Small molecular measurement,Phenytoin,TDM, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 本研究主要針對治療癲癇症之藥物苯妥英(Phenytoin)血液中藥物濃度監測開發即時偵測微型生物晶片。苯妥英在血液中之有效治療濃度區間非常狹窄,且治療劑量與中毒劑量非常接近,因此,需要一個微型感測器密集的監測血液中的藥物濃度。根據全國藥物不良反應通報中心統計,苯妥英藥物不良通報數名列前十,是藥物治療監測(TDM)的重要監測藥物之一。
現行檢測小分子藥物之檢驗儀器體積龐大、費用昂貴,檢驗流程繁瑣無法即時檢測,容易錯估病人的病情或造成藥物副作用的產生,且隨健康意識的抬頭,針對微型化之即時感測器的需求也日益提升,而壓阻式力學感測器具有即時量測小分子藥物之潛力,於是本研究開發以力學基礎量測的生物感測晶片,以壓阻式微懸臂樑感測器為基礎,改良設計一個橋狀薄膜結構,增強結構上的穩定而不失去訊號靈敏度,利用 CIC下線方式製作標準 CMOS 製程壓阻式橋狀薄膜感測晶片,此外,為求此生物感測器可落實便利性,以低成本的方式進行密閉式封裝,提供感測器一個固定的量測環境,製作一個低成本、微型化、高靈敏度、可定量檢測、使用微量檢體且可即時監測之小分子藥物生物感測器。 本研究利用抗體與抗原間的專一性鍵結固定待測藥物苯妥英於橋狀薄膜表面,鍵結時產生的分子構型變化使橋狀薄膜產生應力應變,透過壓阻材料來產生電訊號的改變,因此不受限於小分子藥物的質量限制。由實驗結果得知橋狀薄膜感測器較微懸臂樑感測器提升了約8倍的訊號改變量,且成功對濃度為5 ug/mL、10 ug/mL、35 ug/mL、50 ug/mL、100 ug/mL的本妥英藥物進行定量量測,得到藥物濃度對電阻變化量之線性曲線。本研究壓阻式橋狀薄膜生物感測器之可量測最小濃度(LOD)為5.69 μg/mL,可定量最小濃度(LOQ)為27.35 μg/mL,可量測濃度區間為5.69 μg/mL ~100 μg/mL,苯妥英有效濃度範圍均落在量測濃度區間內,證實本研究之壓阻式橋狀薄膜生物感測器在量測小分子藥物上具有一定的潛力且擁有定量分析之能力。 This study focused on the development of pizoresistive membrane-bridge to monitor the concentration of Phenytoin in blood. Phenytoin is a widely used drug for the treatment of epilepsy. The effective therapeutic concentration range of phenytoin in the blood is very narrow, and the therapeutic dose is very close to the toxic dose. Therefore, a micro-sensor is needed to monitor the concentration of the drug in the blood intensively. According to the National Adverse Drug Reactions (ADRs) Reporting System, the number of phenytoin adverse drug notifications ranked in the top ten.It’s one of the important drugs for drug treatment monitoring (TDM). The current testing instruments for detecting small molecule drugs are bulky and expensive. The inspection process is complicated and undetected immediately. It is easy to misdiagnose the patient's condition or cause side effects of the drug. With the rise of health awareness, the demand for miniaturized sensor is increasing, and the piezoresistive mechanical sensor has the potential to measure small molecule drugs in real time. Therefore, this study develops a biosensor on mechanical basis measurement. Based on a piezoresistive microcantilever sensor, an improved membrane-bridge structure is designed to enhance structural stability without losing signal sensitivity. The Piezoresistive membrane-bridge made by TSMC CMOS MEMS 0.35 standard process, and a low cost, hermetic package that provides a stable measurement environment for the sensor. The Piezoresistive membrane-bridge is a small molecule drag biosensor with low cost, miniaturization, high sensitivity, quantitative detection and small amount of sample for real time monitoring. By comparing the experimental result, the membrane-bridge sensor has about 8 times more signal than the Microcantilever sensor. The membrane-bridge biosensor successfully measured the different concentration of Phenytoin which contain 5 ug/mL、10 ug/mL、35 ug/mL、50 ug/mL、100 ug/mL . A linear curve of drug concentration versus resistance change is obtained. The effective therapeutic concentration range of phenytoin was within the measurement concentration range, which confirmed that the piezoresistive membrane-bridge biosensor of this study has certain potential in measuring small molecule drugs and has the ability of quantitative analysis. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79032 |
DOI: | 10.6342/NTU201801372 |
全文授權: | 有償授權 |
電子全文公開日期: | 2023-08-21 |
顯示於系所單位: | 應用力學研究所 |
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