在生醫檢測上，由於生物分子本身的重量或體積極微小，或偵測之生理濃度極低，朝向更高偵測極限(detection limit)的目標發展是有其必要性，有鑑於此，本論文利用高靈敏度的感測轉換元件(螢光標記或非標記)與發展精密的光電訊號處理器，來提高量測系統的解析度。 首先開發出ㄧ個應用於生醫檢測的光電偵測儀，以光電倍增管(photomultiplier tube，PMT)作為光感測器，將類比的電流轉電壓放大器、數位電路以及通用串列傳輸介面(universal serial bus，USB)成功整合在一起，目前此系統已成功量測10-16W的微小光訊號，並已安裝於冷光儀與螢光掃描儀上。 另外，利用電泳微流體生物晶片來驗證振幅調變搭配鎖相放大技術，來提高系統的訊噪比，其中並以雙相位鎖相放大技術偵測其螢光訊號，成功將螢光濃度偵測極限相較於傳統系統提高二十倍以上。鎖相放大器為非常關鍵的光電鍵儀器，故以實驗室自行發展的數位訊號處理(digital aignal processing，DSP)應用卡為基礎，搭配週邊電路完成數位鎖相放大器的原型機，並結合USB 2.0高速傳輸介面作為與電腦端的傳輸介面，實現具有即時資料傳輸功能的數位鎖相放大器。 運用上述關鍵光電訊號處理器，我們在光電生醫量測儀器上的開發，鎖定於與表面電漿共振(surface plasmon resonance，SPR)感測技術結合，開發出不需標記、高靈敏度的表面電漿共振共光程(common-path)外差式干涉儀(heterodyne interferometer)，並以氮氣和氬氣校正系統的解析度，此技術目前可偵測至1×10-6以下的折射係數改變量。另外，我們也比較磁光調變器和電光調變器所調製出的外差光源偵測上的差異性。最後，將單點量測系統推廣至二維全域式(full-field)的量測系統。 Owing to the tiny molecular weight and volume of biomolecules and very low physiologic concentration in biomolecular interaction analysis, it is important to improve the detection limit of biosensing. In this thesis, we integrate high sensitivity transducers (with or without fluorescence label) and developed electro-optical (E-O) signal processors to enhance the resolution of optical metrology system. First, we develop an E-O detector in bio-medical detecting application. The E-O detector combines with a photomultiplier tube sensor and a developed circuit board including the analog current amplifier, analog to digital converter, and universal serial bus (USB) interface. The detector now can measure the light power down to 10-16W and has been used in the bio-luminescence system and biochip fluorescent scanning reader. Moreover, a microfluid biochip is used to verify and the signal-to-noise ratio of the fluorescent signal is improved with the amplitude modulation lock-in amplifying technique with the help of dual-phase lock-in amplifier, and therefore the detection limit of the fluorescence measurement is improved with 20 times better then that of a conventional system. Lock-in amplifier is a key E-O device, so, we develop a home-made digital lock-in amplifier based on a home-made 32-bit digital signal processing board with USB 2.0 interface to realize the digital lock-in amplifier technique in real-time data transmission. To develop label-free biosensing systems, we focus on high sensitivity surface plasmon resonance (SPR) biosensing to build a common-path SPR heterodyne interferometer with the above E-O devices. The SPR interferometer can detect the refractive index change of better than 10-6 by testing the nitrogen and argon gases. Besides, we compare the difference between the magneto-optical and E-O modulation light sources. Finally, a prototype of full-field heterodyne interferometer is developed.
