为了实现对生物分子间相互作用过程的实时、灵敏、快速监测, 获得生物分子的有无、浓度与相互作用的动力学参数信息, 本文设计了基于光纤生物传感器的生物亲和性检测方法。首先, 针对光干涉生物亲和性传感检测系统的光学传输系统“Y”型分叉光纤与光纤探针之间的耦合问题, 提出了自聚焦透镜与石英光纤耦合结构, 该耦合结构偏心公差能够达到002 mm, 倾斜公差能够达到01°; 针对干涉光谱信号的高频噪声问题, 采用一种改进的经验模态分解干涉光谱信号处理方法, 有效避免了干涉光谱曲线滤波处理后极值点位置的偏移; 同时采用局部拟合极值点计算生物分子膜层厚度的方法, 将生物分子膜层厚度的分辨率提高到50 pm。利用所搭建的光干涉生物亲和性检测系统, 建立了HER3-IgG1抗体药物利用金纳米粒子进行信号放大, 实现对其浓度进行定量检测的新方法, 检测过程中无需清洗, 不产生交叉污染。实验结果表明: 系统检测限能达到0082 6 μg/mL, 该系统具有检测时间短, 测量准确、精度高、成本低廉等特点, 能够应用于药代动力学研究中。

In order to realize the real-time, sensitively and rapid monitoring of the interactions between biomolecules, and obtain kinetic parameters of biomolecules existence, concentration and interaction, an affinity detection method based on fiber biosensor is designed in this paper. Firstly, a coupling structure between a self-focusing lens and a quartz fiber is proposed for the coupling problem between the optical transmission system “Y”-type bifurcated optical fiber and the fiber probe in the optical interference bio-affinity sensing system. The coupling structure has an eccentricity tolerance of up to 0.02 mm, and a tilt tolerance of 0.1°. In order to solve the problem of high frequency noise of the interference spectrum, an improved EMD interference spectral signal processing method is adopted to effectively avoid the deviation of the extreme point position after filtering of interference spectral curves; at the same time, method for calculating the thickness of biomolecule film layer by using locally fitted extreme points is adopted to increase the resolution of the biofilm layer thickness to 50 pm. Using the established light interference bio-affinity detection system, a new method for the detection of concentrations of HER3-IgG1 antibody using gold nanoparticles for signal amplification was established. There was no need for cleaning and no cross-contamination will occur during the detection process. The experimental results show that the detection limit of the system reaches 0.0826μg/ml. Due to the advantages of short detection time, accurate measurement, high precision, and low cost, the system is suitable for the study of pharmacokinetics.