A Four-Dimensional (4D) Microchip for Proteomics

摘要提案标题：用于蛋白质组学的四维（4D）微芯片，提案编号：CTS-0626471，主要研究者：Cornelius F. Ivory，机构：华盛顿州立大学摘要：该项目旨在开发一种替代策略，设计ND分离平台，强调并行操作和自锐化分离协议。该提案分为三项任务，首先将对大约12个1D分离进行调整，以在PDMS平台上运行。第二个任务是演示如何将分级峰从一个分离维度移动到下一个，第三个任务将涉及4D微芯片的设计。该项目是分离科学能力的一次雄心勃勃的飞跃。可靠地分离成千上万的蛋白质，没有重叠和足够窄的带宽，将是任何蛋白质组研究的基石。这是因为分析具有重叠蛋白质的洗脱液在质谱中引入了不可接受的不确定性（并可能误导研究人员）。在大规模并行方案中将微流体与色谱分离的深入知识相结合是至关重要的。虽然不可否认的是，一个完整的4-D系统将不会被制造，PI明智地选择探索最重要的挑战，使用最先进的色谱技术应用于微流体集成。该团队的业绩记录值得注意。微加工、表面化学和色谱专业知识的结合是该项目成功的理想选择。在化学/运输问题的洞察力和多维整合的策略是非常有前途的。从更广泛的影响角度来看，成功开发大规模并行级联分离系统将成为人类蛋白质组编目的基石。这样的成功将是对许多疾病的医学治疗的突破。该方案也可以应用于医学诊断。在级联分离中获得的见解可以应用于更高容量的制药工艺。该项目将直接资助2名研究生。此外，每年3+本科生也将在工作组。预计通过NSF-SWEET计划和NSF-REU计划的本科生将为教师参与提供额外的支持。总的来说，该建议将为各种各样的人提供优质教育机会。_ Eric S. Peterson，Program Director（1417）日期

Abstract Proposal Title: A Four Dimensional (4D) Microchip for Proteomics, Proposal Number: CTS-0626471, Principal Investigator: Cornelius F. Ivory, Institution: Washington State University Abstract:The project aims at developing an alternative strategy for designing nD separations platforms that emphasizes parallel operation and self-sharpening separation protocols. The proposal is divided into three tasks, first approximately one dozen 1D separations will be adapted to operate on a PDMS platform. The second task is a demonstration of how to move fractionated peaks from one separation dimension to the next, and the third task will involve design of a 4D microchip. This project is an ambitious leap forward in the capabilities of separation science. Reliable separations of tens of thousands of proteins, without overlap and of sufficiently narrow band width, would be the cornerstone of any proteome study. This is because analyzing eluates with overlapping proteins introduce unacceptable uncertainty (and possibly mislead researchers) in the mass spectra. The coupling of micro-fluidics in a massively parallel scheme with a deep knowledge of chromatographic separations is critical. Though admittedly a complete 4-D system would not be fabricated, the PI wisely chose to explore the most significant challenges to the integration using the most cutting edge chromatographic techniques applied to micro-fluidics. The track record of the team is noteworthy. The combination of microfabrication, surface chemistry and chromographic expertise is ideal for the success of this project. The insight in the chemical/transport problems and the strategy for multi-dimensional integration is highly promising. From a broader impacts perspective, success in developing a massively parallel cascade separation system will be a cornerstone for enabling the cataloging of the human proteome. Such success will be a breakthrough for the development of medical treatments for a vast number of illnesses. The scheme can also be applied to medical diagnostics. Insight gained in cascade separations can be applied to higher volume pharmaceutical processes. The proposal will directly support 2 graduate students. Additionally, 3+ undergraduate students per year will also be in the working group. Additional support for teacher participation via the NSF-SWEET program is expected and undergraduates under the NSF-REU program. Overall, the proposal will provide quality educational opportunities to a wide range of individuals._______________________________________Eric S. Peterson, Program Director (1417) Date