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. ? ? ?
