多重感測元件之高性能壓阻式微懸臂梁生化感測器 之設計、製程與特性分析

Abstract

近年來隨著生物科技與微系統技術的發展，且在走向高齡化的社會趨勢下，可攜式生醫檢測晶片的市場與需求日益增大。其中生醫檢測晶片是利用微奈米機電系統技術平台，所發展出跨領域整合式系統，其特性具有微小化、可攜式、高靈敏度、少量檢體、免螢光標定及快速檢測的優點，不同於過去傳統笨重、高成本、速度緩慢的檢驗設備。 本研究以力學為出發點，應用在生物標記蛋白質上的的偵測，藉由生物分子專一性的鍵結特性，在懸臂樑表面所形成的表面應力來進行量側，使用壓阻式的微懸臂梁架構將訊號讀出與分析。除了延續本實驗室先前所發展出可在變溫環境下的量測技術外，本研究為提升壓阻式懸臂梁感測器的性能，除了在製程設計上的改良與修正，以提升感測器的靈敏度與穩定性。並將壓阻式微懸臂樑感測器推廣成微陣列形式，希望透過陣列式的微懸臂梁系統，將量測訊號進行疊加處理後，能夠有效提升量測之訊雜比，以利後續的分析與判讀。並且將其陣列化的微懸臂樑感測器，應用在後續的生物實驗量測上，透過C反應蛋白的定量實驗，可量測到1μg/ml的低濃度，驗證多重感測元件的量測系統，對於量測解析度的提升以及定量量測誤差上的縮小有顯著的貢獻。本論文成功研發出一具有高靈敏度、高解析度、高可靠度，能夠進行即時量測分析的多重感測元件壓阻式微懸臂梁生化感測系統。

As most countries turns into the ageing societies, biological sensing devices are increasingly needed telemedicine/telehealth. Microcantilever biosensors based on microsystem technologies offer advantages over conventional instruments on miniaturization, label-free feature, portability, real-time rapid diagnosis, and potential low cost. Meanwhile, the biosensor utilizes biomolecular specificity and recognition that can be transferred into surface stresses of nanomechanics on microcantilevers. The piezoresistive microcantilever is chosen for signal transduction and signal analysis. The drawback of temperature-sensitive effect for microcantilever biosensors can be eliminated by the self-thermal compensation approach developed in our research group. Multiple sensing elements of microcantilever biosensors are newly developed in this study to significantly reduce the noise level and enhance signals of multiple sensing microcantilevers. The measurement of C-reactive protein has been conducted to detect a concentration level of 1μg/ml. This work shows the capability, sensitivity and manufacturing stability of results for multiple sensing microcantilever biosensors. The SEM picture has also been demonstrated to show the improved design and fabrication of multiple sensing microcantilevers. In comparison to conventionally bulky and heavy biosensing instruments, the piezoresistive multiple sensing microcantilever biosensors have great advantages of miniaturization and real-time on-site detection, and show the potential in telemedicine/telehealth.