基于长周期光栅表面结构优化的甲胎蛋白检测技术研究

The long period fiber gratings are a new class of optical sensors which can implement remote, real-time, in situ monitor for biochemical molecules, but there are some defects such as low sensitivity, weak specificity of molecular identification and poor reliability. The project intends to be geared to the needs of the major national disease security, use detection of early liver cancer as goal, select its main marker alpha-fetoprotein as the research object, utilize long period fiber grating as the detection device, establish a rapid, sensitive, non-destructive new method of detection alpha-fetoprotein. In this project, through theoretical designs, the optimal grating structure and film structure will be obtained, and the sequencing assembly coating technology is used to modify the long period fiber grating. The sensitivity will be improved and detection signal will be amplified by screening nanomaterials and optimizing the micro-nano structure of long period fiber grating surface. Its surface performance will be enhanced through some methods such as self-assembly, covalent crosslink, and so on. The poor selectivity will be solved by preparing nano-bio-functional film with good specificity. The sensing mechanism, law, and influencing factors of the grating coated films to the refractive index will be researched by the numbers through simulation of optical theory and molecular dynamics, the optimized conditions of detection alpha-fetoprotein will be builded in order to improve the reliability and stability of the detection. The study results will provide a major analytical tool for the diagnosis and treatment of liver cancer and other diseases, also provide a scientific basis and lay a solid foundation for detection of other biological macromolecules and environmental small molecules.

长周期光栅是一种可以对生化分子实施远程、实时、原位监测的新型光学传感器，但存在灵敏度低、分子特异识别能力弱及可靠性差等缺陷。本项目拟面向国家重大疾病安全需求，以肝癌早期检测为目标，选取其主要标志物甲胎蛋白为研究对象，以长周期光栅为检测器件，建立快速、灵敏、无损检测甲胎蛋白的新方法。本项目通过理论设计，优化出最佳的光栅结构及覆膜结构，采用程序化组装覆膜技术对光栅修饰改性。通过筛选纳米材料和优化表面微纳结构提高其灵敏度、放大检测信号；通过自组装、共价交联等方法提升其表面功能，制备特异性良好的纳米生物功能膜，解决其选择性差的问题；并结合分子动力学、光学理论模拟，对覆膜光栅的折射率传感机理、规律和影响因素等开展系统研究，构建检测甲胎蛋白的最优化条件，改善其检测的可靠性和稳定性。本研究成果将为肝癌等疾病的诊断和治疗提供一种主要分析工具，为检测其它生物大分子、环境小分子的研究提供科学依据和奠定基础。

长周期光纤光栅具有体积小、与光纤易兼容、抗电磁干扰、灵敏度高等优点，但其存在对水溶液范围内的折射率灵敏度低的缺点，限制了其在传感领域进一步的应用。本项目通过在长周期光栅表面修饰纳米材料，改善其缺点，调制其折射率灵敏度，并对其在生物分子的检测应用方面展开了一些基础研究。具体来说，本项目所开展长周期光栅折射率传感的研究工作主要包括如下几方面：(1).本项目首先利用耦合模理论与MATLAB软件建立了覆膜长周期光纤光栅折射率传感理论模型，系统研究了覆膜长周期光纤光栅的传感机理，纳米薄膜与不同周期的长周期光栅作用时的内在机理，为长周期光栅表面纳米材料修饰的设计提供了良好的理论指导；(2). 通过在长周期光栅表面修饰纳米材料及系统的实验，改进LPFG结构，探索了提高长周期光栅折射率传感灵敏度的方法，并比较研究了不同纳米材料及纳米结构修饰对长周期光栅透射谱的影响，拓展了长周期光栅检测折射率的范围及应用领域；(3). 利用自组装和热合成技术，在长周期光栅表面制备了纳米孔、纳米花、纳米线阵列等微纳结构，调制长周期光栅的透射谱；(4). 另外，项目展开了长周期光纤光栅在生物分子检测方面的基础应用探索研究，利用长周期光纤光栅的耦合特性和光学特性，建立了以长周期光栅为检测器件检测生物分子甲胎蛋白的一种方法，研究了谐振波长随甲胎蛋白浓度变化的变化规律及对甲胎蛋白的选择性能。本研究成果将为肝癌等疾病的诊断和治疗提供一种主要分析工具，为检测其它生物大分子、环境小分子的研究提供了良好的科学依据和奠定了良好的基础，具有重要的学术和实用意义。