設計與研製矽基片上具流道之創新型高靈敏度積體光波導表面電漿子共振(SPR)感測晶片於登革熱病毒及蛋白激酶活性之檢測

Abstract

本計畫之目的在基於過去數年之成果，設計與研製矽基片上具流道之創新型高靈敏 度積體光波導表面電漿子共振(surface plasmon resonance, SPR)感測晶片於登革熱病毒 及蛋白激酶活性之檢測。95 年度開始進行相關研究，設計了具流道之創新型積體光波 導表面電漿子共振(SPR)晶片，並初步製作了元件，建立了可方便控制流通生化物質樣 品的量測系統，經量測實驗，証實了檢測生物分子即時反應的功能；96 年基於前一年 的經驗，配合製程設備性能的限制，變更設備的運用，以提高製作元件的穩定度與可靠 度，並作了初步之生物分子固定化及生化反應之探討。之後，陸續製作更多元件，並嘗 試檢測與生醫應用有關之生化樣本。本兩年期計畫，則將擴展經驗與成果，設計與研製 矽基片上具流道之創新型高靈敏度積體光波導表面電漿子共振，進行進一步登革熱病毒 及蛋白激酶活性檢測之生醫應用。在創新結構之抗諧振反射光波導(antiresonant reflecting optical waveguide, ARROW)表面鍍以可產生表面電漿子共振之金屬(如Au、 Ag、Pt 等)，設計光波導模態與其金屬界面間表面電漿子共振模態適當匹配，使於光波 導中傳輸之光訊號，傳輸至鍍有金屬之區域時，耦合至表面電漿子共振波，因生物分子 間的交互作用造成介質等效折射係數改變，使其耦合狀態改變，輸出光訊號因而變化， 以檢測待測生物分子之即時反應。對於不同的生物分子反應感測，其金屬材料、元件結 構、最佳化狀態、生物分子固定化(immobilize)技術與感測性能亦隨著不同，必須詳加 探討以達成感測特性的最佳化。 第一年分兩部份進行：(1)設計及製作元件，進行基本生化檢測；(2)進行登革熱病 毒與蛋白激酶相關生化樣本製備及生化反應相關之研究。第二年則製作元件實際進行登 革熱病毒及於蛋白激酶活性之檢測，並進行必要之優化元件結構與製程；同時，將製 作之元件初步與光纖接合，形成元件之光纖豬尾(pig-tail)之輸入與輸出結構，可以不 須對準而直接以商品化連接器連接光源之光纖輸出與接收器之光纖輸入，易於進行檢 測，以實用化生醫應用。

The purpose of this two-year project is to continue the past projects to design and fabricate novel high-sensitivity Si-Based integrated waveguide surface plasmon resonance (SPR) chips with low channels for Dengue virus and protein kinase activity sensing For these sensors, novel ARROW (antiresonant reflecting optical waveguide) waveguides are coated with specific metals and immobilized with specific biomolecules for sensing desired species. With suitable design, the optical waveguide mode and the SPR mode can be matched, and optical waves propagating in the metal-clad region of the optical waveguide can be coupled to surface plasmon waves (SPW). Any changes of the refractive index of the ambient environment due to biomolecular interactions will cause the change of coupling characteristics and thus change the output power of optical signal. Therefore, we can monitor the output power to detect the target biomolecular interactions. To sense different biomolecular interactions, we must use different metal coating layer and different immobilized ligands. Moreover, the structure and the optimized parameters of sensors are also different. The structure parameters of integrated optical waveguide biochemical sensors can be accurately controlled for mass-production stability. ARROW-type waveguides are new developed integrated optical devices which have the following advantages over conventional waveguides: (1) high coupling efficiency with fibers, (2) good ability to be integrated on high refractive-index substrate, and (3) single-mode operation with low propagation loss. Our research group has been investigating ARROW devices on: (1) optimum coupling design with single-mode fibers, (2) high-efficiency and easy-fabrication power dividers, (3) wavelength multi/demultiplexers, and (4) optical filters. In the past few years, the sensors with Au metals were fabricated and used to do the preliminary measurement experiments. The process has been improved. The first year of this two-year project, devices will be designed and fabricated, and their basic biosensing characterization will be performed. In addition, experiments for sample preparation and biochemical reactions for Dengue virus and protein kinase sensing will be performed. In the second year, The devices will be optimized and really applied for Dengue virus and protein kinase sensing.