- 學位論文
壓阻式微懸臂梁生物感測器之製作與前列腺特異抗原偵測之研究
Fabrication and Prostate Specific Antigen Testing of a Piezoresistive Microcantilever Beam Biosensor
摘要
在現今社會，對於健康照顧及醫療保健是我們所關心的，促使人們投入大量心力在相關研究上。而生物感測器的發展帶動了醫療檢測的整體提升。其在檢測上的優點上有分析靈敏度及專一性高、分析速度快，以及所使用的檢測樣品及試劑體積較少。 前列腺癌號稱西方男性的前三大癌症殺手，前列腺癌亦是台灣前十大癌症的死因之ㄧ（2006）。而前列腺特異抗原（Prostate Specific Antigen）是檢測前列腺癌的一個腫瘤標記，其在臨床診斷上具有高價值性及判斷性。本研究所量測的前列腺特異抗原更可針對此一疾病作健康評估。 而壓阻式微懸臂梁感測器（Piezoresistive Microcantilever Beam），利用其免化學及螢光標定的檢測方法，當生物分子鍵結在微懸臂梁後，會造成表面應力及應變之改變，再利用惠斯同電橋（Wheatstone bridge circuit）精密量測方式配合後端電路的濾波放大而將電壓訊號讀出。此外我們亦可看出其相較於光學式微懸臂梁，更有檢測體積大大縮小的優點。 在本研究中，我們已利用微機電製程製作出壓阻式微懸臂梁生物感測器並對前列腺特異抗原做初步量測。此外，亦對溫度、離子濃度及藥品的空白實驗做檢測，希望使實驗訊號有更合理之解釋。
並列摘要
Prostate cancer is becoming one of the top three major cancer killers for elderly men in the west, and it is also one of the ten major cancers reported of Taiwan in 2006. Prostate specific antigen (PSA) is found to be the most valuable tumor sign of prostate cancer. It has become the highest value of biomarkers in cancers. In this study, the piezoresistive microcantilever is required for operation in a phosphate buffered saline solution or human plasma which is to maintain a specific pH environment of a strong electrolyte. As a result, the device is required to be electrically insulated in solution environment. The selected silicon nitride is used to conform to the requirements for the insulting material. The cantilevers are designed in 150 or 200 μm long, 50 μm wide and about 1.4 μm thick. The integrated piezoresistive resistors are 100 μm long, 50 μm wide and 200 nm thick, and the expected resistance is approximately 4 kΩ. Meanwhile, the gold layer (30 nm thick) coated on the cantilever surface is necessary for chemical reaction of biolinker, and thus the sensing surface of specific protein adsorption and its associated recognition. In addition to the microcantilever device, several important issues need to be considered in height, length, width, and the total volume of the channel, as well as the flow field in the microchannel. In the micro-fluid system, the laminar flow is also required to reduce the noise from vibrations of the cantilever. The biosensor is wire bonded directly on the printed circuit board (PCB) with a height of 470μm, connected to the signal processing device on the PCB. Preliminary result of PSA detection was obtained by this piezoresistive microcantilever. The device is confirmed to be tested in solution environment and thus its preliminary feasibility. More testing is required for further verification in PSA detection.