Collaborative Research: System Optimization and Data Analysis in Two-Dimensional Liquid Chromatography

在化学系化学测量和成像计划的支持下，弗吉尼亚联邦大学的Sarah Rutan教授、明尼苏达大学的Peter Carr教授、Gustavus Adolphus学院的Dwight Stoll教授和他们的团队将应对执行定量全面二维液相色谱(LCxLC)的挑战。这项技术使用两个非常不同的液体分离系统来分离复杂混合物中存在的组成分子，并为分离复杂混合物(如尿液)提供了一种更强大的方法。拟议的研究将使LC成为一种分析小分子代谢物的实用技术，因此将导致更快和更容易地发现疾病和治疗的分子标记。这一研究团队开展的工作的智力价值在于对色谱分离过程的化学变化如何影响结果数据的特征有了基本的了解，了解了这些化学因素如何影响数据分析方法的性能，并调整了数据分析方法以适应这些数据特征。这些努力将把一个充其量是半定量的耗时过程转变为一种快速有效的方法，将为生物标记物鉴定提供准确、定量的结果。这项工作的更广泛影响在于为生物科学家提供所需的工具，以表征不同分子参与者的数量和关系，因为它们根据生长、疾病状态和环境暴露而变化。这项研究将有助于对复杂生物系统的整体理解。这些知识将有助于改进技术，这些技术在了解和治疗疾病、加强农业和保护环境方面具有巨大的前景。为了让学生更容易接触到色谱学的概念，基于在线LC模拟器，将开发一系列动态的在线作业问题。在培养化学和生物专业的研究生和本科生以及博士后学者方面，人力资源开发也是一个重要组成部分。从事这一项目的学生将受益于与三名在分离科学方面有才华和创造性的研究人员的协同工作。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Sarah Rutan at Virginia Commonwealth University, Professor Peter Carr at University of Minnesota, Professor Dwight Stoll at Gustavus Adolphus College and their groups will address the challenges of performing quantitative comprehensive two dimensional liquid chromatography (LCxLC). This technique carries out separations of the component molecules present in complex mixtures using two very different liquid separation systems, and offers a more powerful method for separating complex mixtures such as urine. The proposed research will enable LCxLC to become a practical technique for the analysis of small molecule metabolites, which will therefore lead to more rapid and facile discovery of molecular markers of disease and treatment. The intellectual merit of the work carried out by this team of investigators lies in the development of a fundamental understanding of how changes in the chemistry of the chromatographic separation processes affect the characteristics of the resulting data, developing an understanding how these chemical factors affect the performance of the data analysis methods, and tuning the data analysis methods to adapt to these data features. These efforts will transform a time-consuming process that is at best semi-quantitative, into a rapid and efficient method that will provide precise, quantitative results for biomarker identification.The broader impacts of the work lie in providing biological scientists with the tools needed to characterize the amounts and relationships of various molecular players as they vary depending on growth, disease state and environmental exposure. This research will contribute towards reaching a holistic understanding of complex biological systems. This knowledge will contribute to refined technologies that have tremendous promise for understanding and curing diseases, enhancing agriculture and preserving the environment. In order to make chromatographic concepts more accessible to students, a series of dynamic, online homework problems will be developed based on online LC simulators. There is also a strong component of human resources development in the training of graduate and undergraduate students, and post-doctoral scholars for careers in chemistry and biology. The students working on this project will benefit from the synergy of working with three talented and creative researchers in separation science.