THERAPEUTIC DRUG MONITORING BY CAPILLARY IMMUNOPHORESIS

我们提出的研究的主要目标是将一个在线 毛细管电泳法免疫检测多残留分析 体液中的结构相关药物及其代谢物。 毛细管免疫电泳法作为一种混合分析技术 电泳法的分析能力和免疫选择性 微量治疗性药物的鉴定与定量 复杂样品矩阵中的药物。在比喻为二维 分离系统，以毛细管电泳为第一维度， 根据药物分析物的大小、电学特性的差异来解析它们 电荷和疏水性。免疫反应，作为第二个维度 分离利用抗体的交叉反应性来识别 具有共同结构元素(表位)的药物分析物。 为了实现我们的研究目标，毛细管的三个技术特征 必须解决免疫渗透问题：(一)分离模式的选择 以及电渗控制对分离分辨率的影响。 毛细管电泳法中的药物分析(II) 外加电场强度与毛细管尺寸的关系，以及 溶液离子强度对分析物转移效果的影响 在毛细管后免疫反应器中将药物分析物与抗体混合， 和(Iii)抗原(药物分析物)-抗体的直接检测 通过监测半抗原的荧光偏振进行反应- 竞争免疫分析形式的荧光素结合物(示踪剂)。至 进一步简化药品监测程序，减少与健康有关的 成本，我们的长期目标是展示 毛细管免疫电泳法同时检测多种 单一生物体液样本中的常见滥用药物或治疗药物。 毛细管免疫渗透--治疗药物的革命性方法 监测显示，选择性方面有很大的跳跃前景， 灵敏度和速度超过了目前的分析方法。这个 毛细管免疫电泳法的发展及其成功依赖于 在不同领域建立许多技术里程碑，包括 在本项目中概述，以及未来集成 微机械加工和阵列检测技术。

The main goal of our proposed research is to integrate an on-line immunodetection with capillary electrophoresis for multiresidue analysis of structurally related drugs and their metabolites in body fluids. Capillary immunophoresis as a hybrid analytical technique exhibits the analytical power of electrophoretic separation and immunoselectivity for the identification and quantification of trace amounts of therapeutic drugs in complex sample matrices. In analogy to a two-dimensional separation system, capillary electrophoresis as the first dimension, resolves drug analytes based on differences in their size, electrical charge, and hydrophobicity. Immunoreaction, as the second dimension of separation utilizes the antibody's cross-reactivity for the recognition of drug analytes with a common structural element (epitope). To achieve our research goal, three technical features of capillary immunophoresis have to be addressed: (i) the selection of separation mode and the effect of electroosmotic control on the separation resolution of drug analytes in capillary electrophoresis (ii) the quantitative dependence of applied electric field strengths capillary dimensions, and solution ionic strengths on the effectiveness of analyte transfer and mixing of drug analytes with antibodies in a post-capillary immunoreactor, and (iii) the direct sensing of the antigen (drug analyte)-antibody reaction by monitoring the fluorescence polarization of the hapten- fluorescein conjugate (tracer) in a competitive immunoassay format. To further simplify the drug monitoring procedures and reduce health-related costs, our long-term objective is to demonstrate the potential of capillary immunophoresis for the simultaneous detection of several commonly abused or therapeutic drugs in a single biological fluid sample. Capillary immunophoresis as a revolutionary method for therapeutic drug monitoring shows significant promise for quantum jumps in selectivity, sensitivity, and speed over the current analytical methods. The development of capillary immunophoresis and its success relies on establishing many technical milestones in diverse fields including those outlined in this project as well as the future integration of micromachining and array detection techniques.