Rapid Metabolomic Screening by Microchip CD-ECD

利用 Microchip CD-ECD 进行快速代谢组学筛查

• 批准号: 7271987
• 负责人: Charles S Henry
• 金额: $ 18.66万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-04 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7271987
• 关键词: Adsorption; Affect; Animals; Biological; Biological Assay; Canis familiaris; Cardiovascular Diseases; Chemicals; Chemistry; Complex; Coupled; Data; Detection; Development; Devices; Diagnostic; Diagnostic Procedure; Disease; Disease Marker; Dose; Doxorubicin; Electrochemistry; Electrodes; Enzymes; Fingers; Gas Chromatography; Genetic; Glass; Goals; Health Professional; Lipids; Liquid Chromatography; Malignant Neoplasms; Mass Chromatography; Mass Fragmentography; Mass Spectrum Analysis; Measurement; Medicine; Methods; Metric; Microchip Electrophoresis; Microfluidic Microchips; Modification; Monitor; NMR Spectroscopy; Numbers; Onset of illness; Outcome; Oxidation-Reduction; Physiologic pulse; Plants; Play; Polymers; Preparation; Process; Proteins; Pulse taking; Range; Reporting; Research; Research Personnel; Role; Sampling; Science; Screening procedure; Serum; Serum Markers; Specificity; Spectrometry; Surface; System; Techniques; Technology; Testing; Time; Urine; Work; base; chemotherapy; cost; design; desire; improved; instrument; instrumentation; liquid chromatography mass spectrometry; metabolomics; micro-total analysis system; microchip; miniaturize; novel; novel diagnostics; oxidation; point of care; protein expression; small molecule; tool

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.

描述（由申请人提供）：疾病的发作、进展和治疗导致遗传信息和蛋白质表达和活性的变化。小分子，特别是与氧化还原过程相关的小分子，在疾病的发生、进展和治疗中也起着关键作用，特别是癌症和心血管疾病，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志物，然而，对于小分子来说，情况并非如此。大多数小分子诊断方法集中于一种分析物，基于传统的化学测定或酶测定，并且不提供多分析物检测能力。我们的假设是，检测多种小分子（代谢组学筛查或分析），特别是与氧化还原过程相关的小分子，将为跟踪疾病发作、进展和治疗提供新的诊断工具。我们的目标是在这个项目中开发一个多功能的实验室芯片设备的氧化还原标记物的代谢组学分析。该设备将使用耦合电化学检测与微芯片电泳，以实现我们所期望的结果，并将是唯一的从现有设备的数量和组成的工作添加到系统。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Au或C电极偏置在一个范围内的氧化电位的伏安特性的分析物。第二，我们将表征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，以减少分析物吸附并提高分离效率。一旦我们开发出该仪器，我们将使用它在接受化疗的犬中进行代谢组学分析，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护理点诊断仪器提供一种新的工具，有助于个性化医疗的开发和实施。