2008-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/679756摘要：近十年來，受益於微奈米科技的發展，生物感測器的研發已有重大的進展。其中，微懸臂梁感測器由於對於微小質量靈敏度極高，無傳統螢光標示檢驗法的毒性，且可利用微機電製程做成微小陣列，同時進行多向檢測，實為一非常具有潛力的生物感測器。 免疫分析的原理為偵測因專一性結合的生物分子所產生的物理、化學、光學或電學的訊號。傳統微懸臂梁生物感測器的原理在於量測生物分子結合在梁表面時，因表面應力而導致的梁彎曲變形。由於生物分子結合在感測器表面後會緩慢產生構形變化(conformation change)，導致整個量測時間長達數小時，使得在即時量測的需求上，遠不如其他的感測器(如表面電漿共振感測器及石英微天平共振感測器，來得迅速。相對於傳統的變形量測，共振式微懸臂梁生物感測器則基於頻率量測。此種感測器，不但具有即時偵測的優點，且因為可以激發在高模態下工作，對於微小質量的解析度可高達100ng(1ng=10 的-9 次方克)以上。然而一般生物感測器多置於生物流道內，微懸臂梁在 振動時，容易受到周圍流體黏滯性、虛擬質量、流道壁等多重影響，而使頻率量測品質下降。若將流道置入在內的乾式微懸臂梁，讓微懸臂梁在空氣或真空中振動，應可大幅改善量測品質及精度。 計畫主持人基於過去三年主持的國科會"巨分子力學及其在微感測器之應用"之奈米國家型科技計畫，所累積的懸臂梁感測器的製造、分析、應用之經驗，擬提出一個三年期計畫，借助台大奈米微機電系統研究中心及國家奈米元件實驗室既有之微機電製程能量與設備，改良一般共振式微懸臂梁，並進一步針對新型之乾式內建微流道微懸臂梁質量感測器進行研發與製造，同時整合台大應力所之雷射都卜勒光學振動量測儀(MEMS-AVID)，量測不同生物分子結合在梁表面時，所導致的振動頻率之改變，以用於生物免疫分析。此外，為掌握設計與相關參數量測，亦將建立此一感測器的理論分析及數值模擬模式。運用微機電製程技術、理論分析、數值模擬與相關實驗量測技術，本研究將深入了解微懸臂梁生物感測器之力學機制，並據之得到微懸臂梁生物感測器的最佳化設計。<br> Abstract: The detection of bio-molecules has made a great progress in the recent decade due to the rapid development of nanotechnology. MCB (Micro-cantilever beam sensor) is one of the high resolution sensors developed for immunoassays and can be fabricated in array form for simultaneous detection of multiple targets. The traditional MCB measures the static mechanical bending of the beam tip, due to the surface stress induced by the specific binding of immobilized ligand on the beam surface and analyte in the fluid. However the conformation change of ligand-analyte complex causes the deformation process to last as long as a few hours. The fact renders the traditional MCB less competitive than other real time measuring devices, such as SPR (Surface Plasmon Resonance sensor), and QCM (Quartz Crystal Microbalance sensor). In contrast, the resonant MCB measures the resonance frequency shift due to the added mass of bound analyte and can provide the real time measurement. Moreover, mass as small as 100 ng can be detected using higher resonance modes.However, such a MCB device is conventionally immersed in the fluid and hence suffers from the viscous damping and virtual mass from fluid, which degrades the measurement resolution. The measurement quality and accuracy can be significantly improved if the micro-channel is built in the cantilever beam so that the beam vibrates in air. Based on our previous experience and technique in fabricating micro-cantilever beam sensor, a three-year project is proposed to improve the conventional resonant MCB and further develop a new dry type cantilever beam sensor with built-in fluid micro-channel. Fabrication of MCB will be carried out using the current techniques in the NTU NEMS center and NDL,including photolithography, E-beam deposition, dry etching, and anodic bonding. A microscopic Laser Doppler vibrometer (MEMS-AVID) will be set up to monitor and measure the resonant frequency shift and magnitude of vibration. In addition, 3-D and full time scale numerical simulations will be performed and compared to experiments. With the integration of MEMS fabrication, theoretical and numerical analyses, and measurement techniques,the research will provide a deeper understanding of the mechanics mechanism of MCB sensors, based on which an optimal design can be achieved.微懸梁感測器共振微懸臂樑感測器雷射都卜勒光學振動量測儀Micro-cantilever beam sensorresonant MCBMEMS-AVID高精度共振微懸臂樑感測器之研發(國科會)