壓阻式微懸臂樑生物感測元件於抗癲癇藥物之研究

Abstract

本研究建立於微奈米機電技術(Micro/Nano Electromechanical System Technology)之下，此為一跨領域整合之技術，在近年來廣大市場及生物科技的快速發展之下，正以低成本、高靈敏度、可攜式、微型化、快速、少量檢體與免螢光標記即可檢測的優勢，將逐漸取代傳統大型且高成本的傳統設備，已成為生物領域所研究的重要技術。而本研究分析的藥物為苯妥英(Phenytoin)，此種藥物於行政院衛生署藥品不良反應上，常進前十名的排行榜，可以發現其需要監測之重要性。 為了發展免螢光標定之生物感測器，利用力學基礎在壓阻式微懸臂梁上作為生物訊號之轉換機制，與自組裝分子(SAM)鍵結專一性抗體與藥物，將生物鍵結時對微懸臂梁所產生的表面應力轉換成電阻值輸出。在新設計之下，以金作為溫度感測器用以消除溫度效應，其穩定度比多晶矽壓阻材料好上10~15倍。再加上訊號平均(Signal averaging)之訊號處理，使量測得的訊號解析度提升，在本研究中，四個訊號平均可以提升189%的訊雜比(Signal-to-noise ratio)，藉由雜訊比的提升可以量測到更低濃度的待測物。而在最後的藥物濃度監測中，成功的定性與定量分析出不同濃度的苯妥英10~500 μg/mL，本研究最終之目的是希望可以透過標準半導體製程大量製造並且配合後端電路做到在醫院以外的地方也可做一預防或輔助性的檢驗。

Therapeutic drug monitoring is a growing issue to measure specific drugs at timed intervals in order to maintain a relatively constant concentration of the medication in the bloodstream. This study focus on “Phenytoin” which is related to cardiovascular and brain vascular diseases, and have narrow ranges of drug dosage in the bloodstream. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance. By utilizing MEMS technology, a portable piezoresistive microcantilever biosensor is designed, fabricated, and integrated with a microfluidic channel system to provide immediate and efficient cares for patients at home or bedside point of care. To develop a biosensor with label-free feature, the piezoresistive microcantilever biosensor based on nanomechanics as a transducer for drug detection. Firstly, a self-assemble molecule (SAM) has been utilized to link the gold surface on the sensing surface of a microcantilever, which induces nanomechanics of specific binding. Followed by the second layer of drug-specific antibody, the microcantilever biosensor is ready for drug detection, converting the surface stress-induced deflection into a signal of electrical resistance change. Meanwhile, by using multiple sensing microcantilevers in parallel for detection, the signal to noise ratio is increased by 189% to improve the device performance. The Phenytoin drug concentration of 10~500 μg/mL has been firstly demonstrated to ensure the measurement of drug by using this microcantilever biosensor technology.