基于光泵浦-太赫兹探测的分子自组装石墨烯纳米带抗原靶向识别研究

To realize ultrafast dynamics analysis of antigen-antibody interaction in THz frequency and achieve practical trace signal detection in liquid-phase antibody-targeted antigen identification, this project proposes time-resolved THz spectroscopy methods based on photoexcited molecular self-assembly graphene nanoribbons (GNRs) for the dynamical detection of proto-oncogene C-erbB-2. Particularly, research efforts are first put to design a surface functionalization scheme for antibody and graphene intrinsic structure protection, put forward extraction algorithm of light induced time-resolved conductivity during antibody-antigen binding on GNRs surface, and construct a novel conductivity model based on phonon resonance and the underdamped vibration analysis of liquid-phase protein molecules. Then, according to the obtained optimal model parameters, the numerical features of wave vector and energy transfer of restricted carriers in nanoribbons are extracted, and a signal characterization method is established based on Fano exciton resonance absorption model. With superb spectral resolution and robust prediction results, we expect to demonstrate the ultrasensitive detection mechanisms of antibody-antigen with trace signal; Finally, the above analysis can help formulate the numeric computational method of reorganization energy between antibody and antigen induced by light, capture the energy distribution of carriers in the binary/ ternary system using static and time-dependent tight-binding model respectively, and reveal the nature of light induced reorganization energy between antibody and antigen on GNRs by carrier transport mechanism. This study is expected to inspire the implement of light-control biological process.

为实现太赫兹频段抗原-抗体相互作用的超快时间动力学分析，满足液相抗体靶向识别抗原痕量信号的实际检测需要，本项目提出基于光激发石墨烯纳米带（GNRs）动态检测原癌基因C-erbB-2的时间分辨太赫兹光谱解析方法，实现：1）设计分子自组装的石墨烯纳米带表面功能化方法，建立光泵浦GNRs抗体识别抗原的时间分辨电导率提取算法，通过对液相蛋白质分子欠阻尼振动特征分析，获取耦合局部声子共振效应的电导率模型；2）以最佳模型参数及纳米带载流子受限的波矢、能量传输特征为基本突破口，提出基于Fano激子共振吸收模型的痕量信号表征方法，解析抗体靶向识别痕量抗原的超灵敏检测机制；3）确定光诱导液相抗原-抗体配位点重组能的计算方法，以静态、含时紧束缚模型确定载流子在二/三元体系中的能量分布，论证光诱导GNRs抗原-抗体配位点重组能状态变量的内涵和电子运输机制。该研究有望为实现光调控生物反应过程提供有效的思路和方法。

太赫兹（THz）技术是近年来新兴的一种远红外相干辐射技术，太赫兹光谱在某些生物大分子的结构和动力学特性检测方面有着巨大潜力，可以弥补传统红外光谱技术对于整个分子构型、构象的细微变化不够敏感的不足。为实现太赫兹频段生物分子相互作用动力学分析，满足液相抗体靶向识别抗原痕量信号的实际检测需要，本项目首次提出利用金属光栅负载石墨烯带在全内反射模式下实现电控宽带太赫兹检测技术：该方案将全反射表面倏逝波非共振场增强效应和金属光栅相结合，实现了传统器件性能4.5倍的提升，并进一步制作基于石墨烯表面修饰Au离子复合物的生物传感器。此外，从提升信号传感准确性及灵敏度方面，本项目提出一种以EG掺杂PEDOT/PSS薄膜为抗反射涂层用于提高光谱分辨率的方法，利用EG掺杂浓度为10%的PEDOT/PSS涂层，实现在0.3~1.5 THz宽频范围内电导率几乎与频率无关的效果；进一步采用智能计算，对蛋白沉积薄膜的量化表征进行研究，利用泛函的密度-功能理论计算，实现对4种衍生物分子的动力学分析，为采用机器学习进行太赫兹分子光谱分析提供了一种新手段。.项目按照计划进度正常执行，实际经费支出与预算基本相符，执行期间项目负责人共计发表16篇学术论文，其中包括《Photonics Research》、《Optics Express》、《Biomedical Optics Express》等SCI索引9篇，JCR一区论文7篇，JCR二区论文2篇，申请国家发明专利6项，PCT专利3项，软件著作权登记1项，超过预期目标。