基于超分子介导金属纳米结构增强表面等离子共振的细胞因子免疫传感方法研究

With the acceleration of the process of modernization, severe neurological disease has been rising recently, which has brought great loss to the society. It was found that the concentration of cytokines CX3CL1 is closely related to these severe neural pathological processes. This proposal intends to build a new highly sensitive nano sensors to monitor CX3CL1 in real-time in patients’ cerebrospinal fluid and urine. And then through exposing the central mechanism of severe neural disease pathology process, this proposal will provide the data base for the monitoring and treatment of the disease. Gold nanoparticle (AuNP) has good biocompatibility and is easy to be modified with other functional group on its surface. Conjugation of AuNPs and supramolecular macrocycles significantly combines and enhances the characteristics of the two entities, such as the electronic, thermal, and catalytic properties of AuNPs and molecular recognition of the macrocyclic hosts, expanding potential applications as nanosensors. To improve the sensitivity of surface plasmon resonance (SPR) biosensors, this proposal design a novel strategy in which AuNPs are assembly immobilized on the gold film through the host-guest interaction layer by layer. Anti- CX3CL1 can be adsorbed on the host molecules monolayer orientedly. The fabricated 3D Nano structure serves as sensitive layer to enhance the SPR signal for following CX3CL1 immunoassay. This proposal will study the effect of nanoparticle size and gap on the enhancement of SPR signal, providing the basic data and theoretical basis for further research on 3D AuNPs as the sensor signal amplifying materials. Through the detection of CX3CL1 in patients’ urine and cerebrospinal fluid in real-time, it reveals the corresponding relation between the CX3CL1 concentration in the urine and the progression of the disease. To the end, develop a new method for early warning and diagnosis and treatment of patients with severe neurological diseases.

随着现代化进程的加快，神经疾病激增，给社会和家庭带来巨大损失和压力。由于其病理过程与细胞因子CX3CL1紧密相关，本项目以生物相容性较好的金纳米颗粒（AuNPs）为目标化合物，采用超分子介导自组装三维纳米结构（3D-AuNPs）作为增敏层，开展基于3D-AuNPs构建高灵敏CX3CL1表面等离子共振（SPR）传感器的研究。首先考察超分子介导3D-AuNPs和自聚集AuNPs对抗体分子吸附的影响，并通过对芯片表面三维纳米结构的有序性、AuNPs的粒径和间隙对SPR信号和反应动力学的影响研究，探讨3D-AuNPs光学效应增强SPR信号的机理，为3D-AuNPs作为传感器信号放大元件的深入研究提供基础数据和理论依据。通过实时检测神经重症病人尿液和脑脊液中CX3CL1浓度变化，揭示其与病程发展的相应关系，进一步为临床神经疾病患者的早期预警和诊断治疗提供新方法。

本项目以神经重症病为研究对象，开发了灵敏、简便诊断神经重症病的传感器。以生物相容性较好的金纳米颗粒（AuNPs）和抗体为目标化合物，采用超分子介导自组装三维纳米结构（3D-AuNPs）作为增敏层，开展基于3D-AuNPs构建高灵敏CX3CL1传感器的研究。首先考察有序3D-AuNPs和无序堆积AuNPs对抗体分子吸附的影响，同时通过对芯片表面三维纳米结构有序性、AuNPs的粒径和间隙对SPR信号和反应动力学的影响研究，探讨3D-AuNPs光复合效应增强SPR信号的机理，为三维AuNPs作为传感器信号放大材料的深入研究提供基础数据和理论依据，通过实时检测神经重症病人尿液中和脑脊液的CX3CL1浓度，开拓临床神经重症患者的早期预警和诊断治疗新方法。本项目还研究了其他多功能纳米材料比如等离子体磁性纳米材料和二维金属有机框架作为增强元件在SPR中的应用，并成功的构建了疾病检测免疫芯片。