藉由對各種模態的表面電漿共振(surface plasmon resonance，SPR)生物感測器之靈敏度加以分析比對。目前，不論何種組態之SPR生物感測器其偵測極限大約為1 pg/mm2的生物分子表面覆蓋度，難以偵測低濃度之微小生物分子的交互作用情形。因此，本論文提出一種含有金奈米粒子強化(Au nanoparticle-enhanced)之SPR生物感測器光學量測系統，經實驗證實其偵測解析度有機會降低至100 fg/mm2。此嶄新式奈米粒子強化之超高解析度SPR生物感測器透過Maxwell-Garnett模態理論及Fresnel方程式來分析設計，並經由RF co-sputter鍍膜技術製作。將可應用到新藥研發、基因定序、醫療診斷等領域上，並且此奈米粒子強化之超高解析度SPR生物感測器事先不須經額外標記(label-free)，即可直接分析微量生物分子間交互作用分析(biomolecular interaction analysis，BIA)，將成為生物醫學領域上最重要的篩檢感測器。 在生物分子交互作用分析的應用上，分別對於去氧核糖核酸分子雜交(DNA hybridization)反應動力學之研究，並利用外加電場效應降低雜交反應時間，加速生物晶片檢測的速率。以及探討蛋白質分子的吸附動力學。並將SPR技術應用到新興的分子拓印高分子(molecular imprinted polymer，MIP)晶片篩檢上。經由上述的動力學研究，將可建立一完整生物分子行為之作用機制技術平台，將提昇藥物設計與蛋白質體學(proteomics)研究之能力。 Theoretically, simulate and compare the sensitivity of any mode of the existing thin film surface plasmon resonance (SPR) biosensors. No matter which mode of the existing thin film SPR biosensors such as convential SPR biosesor, couple plasmon-waveguide resonance (CPWR) biosesor, and long-range surface plasmon resonance (LRSPR) biosesor, the detection resolution is limited to approximately 1 pg/mm2 of biomolecular surface coverage. Under this constrain, small biomolecular interactions in low concentration are hard to be analyzed. Hence, by increasing the enhancement factor of SPR through metal nanoparticles and eliminating sensing noise with the optical differential metrology system, we demonstrate the resolution of Nanoparticle-enhanced SPR biosensors for detecting the surface coverage of biomaterial down to 100 fg/mm2. The novel nanoparticle-enhanced ultrahigh-resolution SPR biosensors are designed based on the Maxwell-Garnett model and Fresnel equations, and are fabricated by using the RF co-sputter deposition. Therefore, the nanoparticle-enhanced ultrahigh-resolution SPR biosensors can directly analyze tiny biomolecular interactions without adding labels and they will likely become the most important sensing device in the field of biomolecular diagnosis. About biomolecular interaction analysis (BIA), focus on the kinetics of DNA hybridization, then also utilize electric field to reduce time of hybridization and will be able to speed up the rate of detection of biochip greatly, the fundamental study of adsorption kinetics of protein molecules. Furthermore, apply this technology to detection of novel molecular imprinted polymer (MIP) chip. Provide systematical information of interaction mechanism and kinetics of processes of biomolecules and advance the ability of drug design, proteomics study.
