基於角度式檢測之干涉式相位表面電漿子共振感測器

Abstract

在生物傳感器中，相位干涉式表面電漿子共振的成像傳感器因具備著優異的靈敏度廣泛應用於生物分子之檢測。然而，其狹窄的線性量測範圍使可修飾之生物樣品受到了限制。相對於此，基於振幅響應之角度式表面電漿子共振成像感測器提供了較為寬闊的線性區域。從眾多文獻探討後發現，基於相位干涉式響應之角度式表面電漿子共振成像感測器至今仍少有被提出。 本論文提出一基於角度式之相位干涉式全像感測器，將結合可調變波長之垂直共振腔面設雷射二極體以及雙折射晶體，達到相位調變的功效。在此角度式之相位干涉式儀中，雙折射晶體將誘發P 與S 偏振波產生不同軸向之相位差，並經由極化片將此相位差投影至同一平面使得干涉現象之生成。為了實現角度式檢測，本研究採用一帶有視場角約為0.88 度之柱狀凸透鏡，並透過影像感應器擷取出帶有角度資訊之干涉影像。基於電流調變驅動雷射以建立帶有特定相位調變深度為3.832 弧度之正弦相位調變器，本研究可根據團隊先前已獲有專利之泛用式鎖相放大器從此系統中擷取出振幅和相位資訊，並透過一系列演算法取得角度偏移之資訊。 為了驗證本研究所提出系統架構之可行性，我們採用四層膜之晶片模型放置於系統中進行檢測，並將雜交鏈反應施行於本實驗室另一台相位式全像感測器中作為探討。透過將菲涅耳理論應用於擬和模型與實驗結果進行分析後，本研究根據雜交鏈反應結果在相位式全像感測器再一次呈現出相位檢測上受限於狹窄之線性範圍而難以衍伸之偵測極限。此外，本研究於系統上初步驗證出角度式系統之靈敏度雖會受到不同之光源波長以及粘附材料影響表現性，然而基於同一光源與材料下，不同之蒸鍍金屬厚度卻能在角度響應於折射率之關係中呈現極為線性與穩定之現象，此特性大大克服了相位全像式感測器之檢測限制。

Biosensors based on imaging Surface Plasmon Resonance (iSPR) with a phase-sensitive detection system have been widely applied in the detection of biomolecules due to their superior sensitivity. However, its narrow linear detecting range limits the modifying kinds of biological samples. In contrast, the angle interrogation iSPR sensors based on amplitude response have demonstrated a relatively wide linear range. From the discussion of literatures, it has been found that that an angle interrogation iSPR sensor based on phase response has not been proposed. Based on this, an angle-based phase sensitive holographic SPR sensor is proposed. Within this system, a wavelength-tunable Vertical Cavity Surface Emitting Laser (VCSEL) diode and a birefringent crystal are able to achieve a phase modulation on an angle-based phase sensitive system. On the basis of the current modulation, the laser diode aims to establish a simusoidal phase modulation with a critical phase modulation depth of 3.832 radians, which is a key point applied in a patented generalized Lock-in Amplifier (GLIA) to demodulate phase and amplitude information from an interferometric signal captured by a polarimetry. In this angle based phase sensitive configuration, a birefringent crystal induces a phase lag between polarized P and S waves in different axial direction. With an analyzer, there is an interference formed due to the projection of these two polarized waves. In order to implement an angle interrogation, a cylindrical convex lens with a field angle of 0.88 degrees is utilized. Eventually, the interferometric signal with angle information can be recorded by a Charge-Coupled device (CCD) camera. In order to verify the feasibility of this proposed system, a four-layer film model is used in the system. Furthermore, a hybridization chain reaction is implemented in on the previous phase-sensitive holographic SPR system. Through applying Fresnel theory in a fitting model to fit the simulating with experimental results, there are two interesting points from the analyzed results. The results of the hybridization chain reaction once again protrudes a limited linear range in phase based phase sensitive iSPR system. Furthermore, our proposed system has initially been verified that although the performance of sensitivity will be affected by different wavelengths of optical source and adhesion materials, the different evaporating metal thickness demonstrates a consistent linear relationship between angle response and refractive index. This feature overcomes the limitation of the phase-based phase sensitive SPR sensors.