基于太赫兹时域光谱技术的蛋白分子检测与分析研究

发布时间：2018-03-23 11:24

本文选题：太赫兹时域光谱　切入点：抗原-抗体相互作用　出处：《深圳大学》2016年硕士论文

【摘要】：太赫兹波是指频率辐射范围在0.1-10 THz的电磁辐射,在电磁波谱上位于微波和红外线之间。由于太赫兹光谱包含了大量与分子振动及转动相关的光谱信息,太赫兹技术在其发展之初就得到广泛的重视。目前已在国防安全、通信和农业领域得到了有效的应用。近年来,随着科研人员对蛋白质分子骨架振动和构型弯曲等集体振动模式的证实,这些对生物分子结构和功能起关键作用的动态能级,正是分布在太赫兹波段,这使得太赫兹光谱可实际应用于研究生物大分子的结构、分子与分子、分子与环境之间的相互作用等,进而对太赫兹技术在分子生物学、结构化学和临床医学检测等领域的应用提出了更高的要求。本文的主要研究内容包括以下几个方面:第一,利用太赫兹时域光谱技术研究了血凝素HA蛋白溶液及其与特异、非特异抗体反应的太赫兹光谱特性。通过化学计量学方法对不同浓度的HA蛋白溶液及其与特异、非特异抗体反应的多个太赫兹光学参数进行主成分分析,确定最优分析参数及最佳光谱预处理方法。结果证明,结合预处理和主成分分析的处理可以实现对太赫兹光电学参数的各个曲线进行了定性与定量分析。第二,基于最优化参数,利用太赫兹时域光谱技术研究了血凝素HA蛋白分子在不同浓度下的分子水合层动态特征,并检测HA蛋白抗原与广谱中和单克隆抗体F10的结合状态。实验结果显示,通过太赫兹光谱来检测H9蛋白与F10反应溶液的介电损耗角正切值可以实现优于传统方法(ELISA检测)的高灵敏度检测。最后,基于石墨烯能隙调控机理,提出了基于石墨烯微米带的高灵敏太赫兹生物传感器设计,在太赫兹时域光谱的有效频率检测范围内,利用COMSOL对该结构进行了仿真分析。仿真结果显示,石墨烯传感器对太赫兹波的透射率会随着蛋白质折射率发生规律性变化,这种规律为我们的探测器提供了有力的理论基础。
[Abstract]:Terahertz wave is electromagnetic radiation with a frequency range of 0.1-10 THz, located between microwave and infrared on the spectrum of electromagnetic waves. Because the terahertz spectrum contains a lot of spectral information related to molecular vibration and rotation, Terahertz technology has received extensive attention since its early development. It has been effectively applied in the fields of national defense security, communications and agriculture. With researchers' confirmation of collective vibrational modes such as skeleton vibration and structural bending of protein molecules, these dynamic energy levels, which play a key role in the structure and function of biological molecules, are distributed in the terahertz band. This allows the terahertz spectrum to be applied to the study of the structure of biological macromolecules, the interaction between molecules and the environment, and the application of terahertz technology in molecular biology. The applications of structural chemistry and clinical medicine have put forward higher requirements. The main contents of this paper include the following aspects: first, the solution and specificity of hemagglutinin HA protein were studied by terahertz time-domain spectroscopy (THz). The characteristics of terahertz spectrum of nonspecific antibody reaction. The principal component analysis of different concentrations of HA protein solution and its optical parameters of specific and nonspecific antibody reaction was carried out by chemometrics. The optimal analytical parameters and the optimal spectral pretreatment method are determined. The results show that the qualitative and quantitative analysis of the various curves of terahertz optoelectronic parameters can be realized by combining the pretreatment with principal component analysis. Based on the optimal parameters, the dynamic characteristics of the molecular hydration layer of hemagglutinin HA protein at different concentrations were studied by terahertz time-domain spectroscopy. The binding status of HA protein antigen with broad-spectrum neutralizing monoclonal antibody F10 was determined. The dielectric loss angle tangent of H9 protein and F10 reaction solution can be detected by terahertz spectroscopy, which is superior to that of traditional Elisa. Finally, based on the mechanism of graphene gap regulation, A highly sensitive terahertz biosensor based on graphene micron band is proposed. In the range of effective frequency detection of terahertz time-domain spectrum, the structure is simulated and analyzed by COMSOL. The simulation results show that, The transmittance of graphene sensor to terahertz wave changes regularly with the refractive index of protein, which provides a theoretical basis for our detector.
【学位授予单位】：深圳大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O629.73;O657.3

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