| 摘要: | 表面電漿共振生物感測器因為擁有及時偵測(real-time measurement)、免標定(label-free)、 高靈敏度等優點，故經常被應用於量測抗體-抗原、蛋白質-蛋白質、去氧核醣核酸之雜交等 生物分子的交互作用。目前主流的表面電漿共振生物感測技術，大致可區分為四種量測方 法：共振角度分析法、共振光強分析法、共振相位分析法、共振波長分析法。一般來說，共 振波長分析法表面電漿共振生物感測器對於強度相干的雜訊較不敏感，所以其解析度通常較 角度或振幅量測式的表面電漿共振生物感測器為佳。但由於共振波長分析法表面電漿共振生 物感測器需要結合光譜儀使用，故在價格與體積上失去競爭力，所以一般商用的表面電漿共 振生物感測器，大多使用共振角度分析法或共振光強分析法。 本計晝預期發展一種時域光譜式的表面電漿共振生物感測器，其利用傅立葉轉換光譜分 析表面電漿共振生物感測器的共振波長。一般分光型光譜儀想要增加解析度，必須使用較窄 的入口狹缝(entrance slit)與空間頻率(spatial frequency)較高的光柵(grating)，但會減弱到達光 偵測器的光強度，進而造成訊號-雜訊比減弱。傅立葉轉換光譜分析法則不然，其解析度和 移動鏡移動的距離成正比，所以當需要高解析度時，只需加長移動鏡移動的距離即可。故我 們預期在等效折射率的量測上，傅立葉轉換光譜式表面電漿共振生物感測器會比傳統頻率域 光譜式的表面電漿共振生物感測器表現出更優異的解析度。 另外，我們會將此具有高靈敏度及高專一性的蛋白質偵測平台用來偵測模擬血清中的蛋 白質。目前臨床上推斷乳癌病患的預後狀況，大部分都是利用切片的方式觀測HER-2的表 現量，但因為無法定量故在偵測的準確性上有限，同時也很容易出現人為量測誤差。本研究 計晝希望能利用發展出的時域光譜式表面電漿共振生物感測器即時量測模擬血清中已知的 乳癌生物標誌如HER-2 ECD、PSA、CEA、CA15-3、CA27-29等，並在其中選擇適當的乳 癌生物標誌，建立生物標誌蛋白質之間的關聯性，期望能發展成為乳癌早期診斷的方法，以 及有效的早期診斷術後復發(recurrence)，進一步提高治療效率。
Nowadays, surface plasmon resonance (SPR) sensors have been widely used to investigate biomolecular interactions including antigen—antibody， protein—protein， and DNA—DNA interactions because of the capabilities for rapid, label-free, highly sensitive, and real-time detection. Several methods have been employed to monitor the excitation of SPR by measuring the light reflected from the sensor interface. Typically, these can be classified as angular，wavelength， intensity, phase modulation. Following the noise analysis, a relatively lower contribution of the correlated noise from spectroscopic systems than amplitude modulation, leads to an improved resolution. Conventionally, spectral-based SPR sensors operate with an optic spectrometer. The resolution of commercial spectrometers can be up to sub-nm but the price is too high. Hence, the purpose of this proposal is to develop a time-domain spectral SPR biosensor based on Fourier transform. A Fourier transform spectrometer offers the important advantages of the accurate wavenumber scale and the attainable high resolution. As a result, a next-generation low-cost, high-sensitivity, and high-specificity SPR biosensor in conjunction with Fourier transform, immunoassay and high-speed data acquisition sub-system can be generally applied both on academic and clinical detection. Currently, breast cancer is the most common women cancer worldwide. Development of early detection technique for breast cancer is important for improving survival rates. According to previous studies, prostate-specific antigen (PSA) overexpression in human breast cancer was directly correlated with the expression of androgen receptor (AR) and progesterone receptor (PR), and inversely correlated with HER-2 overexpression. Generally, the enzyme-linked immunosorbent assay (ELISA) on specific protein detection in serum shows limitation on detection sensitivity of limit of detection (LOD) at an order of 100 pg/mL. In order to improve the detection sensitivity, this proposal will develop a Fourier transform-based surface plasmon resonance biosensor (FT-SPRB) with a high sensitivity. In addition, it is focused on detection capability of tumor markers in mimic human serum for breast cancer and also to develop a correlation algorithm among the tumor markers, such as HER2-ECD and PSA, on bio-signature for breast cancer prognosis and possible diagnosis at early stage. |
