Rapid Metabolomic Screening by Microchip CD-ECD

描述（由申请人提供）：疾病的发生、进展和治疗引起遗传信息和蛋白质表达和活性的变化。小分子，特别是那些与氧化还原过程相关的小分子，在疾病，特别是癌症和心血管疾病的发病、进展和治疗中也起着关键作用，但在很大程度上被忽视了。已经开发了大量新的诊断方法来检测疾病和疾病治疗的遗传和蛋白质标记，但是对于小分子却并非如此。大多数小分子诊断方法侧重于一种分析物，基于传统的化学分析或酶分析，不提供多分析物检测能力。我们的假设是，检测多种小分子（代谢组学筛选或分析），特别是那些与氧化还原过程相关的小分子，将为跟踪疾病的发生、进展和治疗提供一种新的诊断工具。在这个项目中，我们的目标是开发一个多功能的芯片实验室设备，用于氧化还原标记物的代谢组学分析。该设备将使用电化学检测与微芯片电泳的耦合来达到我们期望的结果，并且在添加到系统中的工作的数量和组成方面将是现有设备的独特之处。我们将集成多达4个工作电极。将研究三种不同的检测模式。首先，我们将使用在氧化电位范围内偏置的Au或C电极对分析物进行伏特度量表征。其次，我们将描述一个包含由不同材料制成的电极的系统，其中每种材料具有不同的分析物选择性。最后，我们将探索在多个电极上的多电位脉冲电化学检测波形，以增加我们可以检测的化合物的范围。同时，我们还将开发新的表面改性策略，以减少分析物的吸附，提高分离效率。一旦我们开发出该仪器，我们将使用它对接受化疗的犬进行代谢组学分析，作为研究即时代谢组学分析能力的第一步。我们相信，这项技术将为快速即时诊断仪器提供一种新工具，有助于个性化医疗的开发和实施。

DESCRIPTION (provided by applicant): The onset, progression, and treatment of disease cause changes in genetic information and protein expression and activity. Small molecules, particularly those associated with redox processes, also play a key role in the onset, progression, and treatment of diseases, particularly cancer and cardiovascular disease, but have been largely ignored. A significant number of new diagnostic approaches have been developed to detect genetic and protein markers of disease and disease treatment, however the same is not true of small molecules. Most small molecule diagnostic methods focus on one analyte, are based on either traditional chemical assays or enzyme assays, and do not provide multianalyte detection capacity. It is our hypothesis that detection of multiple small molecules (metabolomic screening or profiling), particularly those associated with redox processes, will provide a new diagnostic tool for tracking disease onset, progression, and treatment. It is our goal in this project to develop a multifunctional lab-on-a-chip device for metabolomic profiling of redox markers. The device will use couple electrochemical detection with microchip electrophoresis to achieve our desired results and will be unique from existing devices in the number and composition of working added to the system. We will integrate as many as 4 working electrodes. Three different detection modes will be investigated. First, we will use Au or C electrodes biased across a range of oxidation potentials for Volta metric characterization of analytes. Second, we will characterize a system containing electrodes made from different materials where each material has a different analyte selectivity. Finally, we will explore multi-potential pulsed electrochemical detection waveforms at multiple electrodes in an effort to increase the range of compounds we can detect. At the same time, we will also develop novel surface modification strategies that reduce analyte adsorption and increase separation efficiency. Once we have developed the instrument, we will use it to perform metabolomic profiling in canines undergoing chemotherapy as an initial step towards investigating the ability of point-of-care metabolomic profiling. We believe this technology will provide a new tool for rapid point-of-care diagnostic instrumentation that will assist in the development and implementation of personalized medicine.