Development of a resonance micro-cantilever beam bio-sensor

隨著半導體製程技術的進步，生醫檢測系統之目標逐漸以將檢測系統與設備微小化、提高穩定度、增加可攜帶性、減少外界環境影響以及降低成本為主。一般檢測的方法是利用化學或螢光標的配合架設光場進行檢測，而本研究以原子力顯微鏡與光纖干涉量測技術為設計基礎，進行共振式微懸臂樑感測器之製作，依類型可分為傳統共振式微懸臂樑生物感測器、分區鍍金之共振式微懸臂樑生物感測器以及開放式微流道之共振式微懸臂樑生物感測器，希望能夠藉由微懸臂樑之共振頻會隨著質量改變而改變的特性，以量測共振頻率偏移來取代螢光標的的檢測方法。其後進行免疫反應實驗來證明本研究成功製作出共振式微懸臂樑生物感測器，經由將感測晶片浸泡在含有待鍵結分子之溶液中做為化學表面修飾方法來鍵結C反應蛋白進行共振頻之量測。本實驗挑選了傳統共振式微懸臂樑生物感測器與分區鍍金之共振式微懸臂樑生物感測器做為檢測對象，選擇1000 μg/mL與1 μg/mL兩種C反應蛋白溶液濃度進行檢測，而根據實驗結果，儘管C反應蛋白濃度不同，在鍵結開始的30分鐘內之共振頻變化即可達到總變化量之66％以上，表示本研究中所提出之共振式微懸臂樑生物感測器製作方法可行。而根據此一系列製程，以及本實驗架構之微小化、低成本、高穩定度、可攜帶性等優點，未來也可繼續朝向微流道共振式微懸臂樑生物感測器之開發做為目標。Based on the atomic force microscopy and the technology of fiber interferometry, this study designed the resonant based micro-cantilever beam bio-sensors which can be classified as traditional resonant micro-cantilever beam bio-sensors, resonant micro-cantilever beam plating with Cr/Au in different block bio-sensors, and suspended microchannel resonator without channel packaging bio-sensors. Based on the fact that the resonant frequency of cantilevers would change with their mass, biomedical detection would be proceed by measuring the resonant frequency shift, and this study chose immune detection technique to detect C-reactive protein (CRP) which was immobilized on micro-cantilever using surface micromachining technique. Two types of sensor-chips, traditional resonant micro-cantilever beam bio-sensors and resonant micro-cantilever beam plating with Cr/Au in different block bio-sensors, were used to detect the different concentrations of CRP solution (1000 μg/mL and 1 μg/mL). A distinct change in the resonant frequency of micro-cantilever was observed as a function of time. Resonant frequency decreased rapidly over 66% from initial value in 30 minutes of C-reactive protein antigen-antibody interacted. As a result, the resonant based micro-cantilever beam bio-sensors in this study offers advantages including the miniaturization of devices, the improvement of stability, the reduction of environmental impacts and costs