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

在化学系化学测量和成像项目的支持下，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解决进行定量综合二维液相色谱（lccxlc）的挑战。该技术使用两种非常不同的液体分离系统对复杂混合物中的组分分子进行分离，并为分离复杂混合物（如尿液）提供了更强大的方法。拟议的研究将使lclc成为分析小分子代谢物的实用技术，因此将导致更快速和更容易地发现疾病和治疗的分子标记。这组研究人员所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所得数据的特征有了基本的认识，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。这些努力将把耗时的半定量过程转变为一种快速有效的方法，为生物标志物鉴定提供精确的定量结果。这项工作的更广泛影响在于为生物科学家提供了表征各种分子参与者的数量和关系所需的工具，因为它们因生长、疾病状态和环境暴露而变化。这项研究将有助于全面了解复杂的生物系统。这些知识将有助于改进技术，这些技术对了解和治疗疾病、加强农业和保护环境具有巨大的希望。为了让学生更容易理解色谱概念，我们将基于在线LC模拟器开发一系列动态的在线作业问题。在培养化学和生物学领域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。参与该项目的学生将受益于与三位才华横溢、富有创造力的分离科学研究人员的合作。

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.