Collaborative Research: Fabrication and Optimization of Continuous Stationary Phase Gradients for Liquid Chromatography

本项目由美国国家科学基金化学学部化学测量与成像项目资助。化学分离的目的是利用一种物质在固定相和流动相之间表现出的相互作用程度的差异，将一种复杂的混合物分离成其单独的组分。在这个项目中，弗吉尼亚联邦大学（VCU）的Maryanne Collinson教授和Sarah Rutan教授正在探索化学分离领域的另一种方法。在分离过程中，不改变流动相的组成，而是改变固定相的组成。固定相的逐渐变化有许多优点，包括提高选择性、分离时间和检测混合物中物种的能力。合作研究小组之间的协同作用增强了本科生和研究生在最先进的材料合成、色谱和模拟提供的预测能力方面的多样化培训。此外，通过与新教师建立同行指导关系，VCU的分析化学本科教学正在得到加强。该项目侧重于以下三个具体目标：(1)设计、构建和表征沿其长度具有连续梯度化学功能的液相色谱柱；(2)开发和实施工具，以预测不同组的分析物在连续梯度固定相上的色谱反应；(3)将模拟与实验相结合，以确定获得最佳分离所需的梯度长度和成分。这样就避免了通常在方法开发中使用的试错方法。为了证明原理，使用硅烷化学和控制速率输注（CRI），对硅整体柱和填充表面多孔颗粒的柱进行战略性修改，以纳入C8， C18，胺和/或苯基的连续梯度，这是Collinson小组最近开发的一种方法。Collinson小组在溶胶-凝胶化学和表面化学梯度方面的专业知识与Rutan小组在分离和液相色谱建模方面的专业知识的整合，正在引领社会相关问题的新方法的发展，从生物标志物的发现到低水平环境污染物的检测。

This project is funded by the Chemical Measurement and Imaging Program of the Division of Chemistry at the National Science Foundation. The goal of a chemical separation is to separate a complex mixture into its individual components by taking advantage of differences in the degree of interaction a species exhibits between a stationary phase and a mobile phase. In this project, Professors Maryanne Collinson and Sarah Rutan at Virginia Commonwealth University (VCU) are exploring an alternate approach in the field of chemical separations. Instead of manipulating the composition of the mobile phase during the course of a separation, the stationary phase composition is instead changed. Gradual changes in stationary phases have many advantages including the ability to improve selectivity, separation times, and the ability to detect species in the mixture. The synergy between the collaborating research groups enhances the training of a diverse body of undergraduate and graduate students in state-of-the-art materials synthesis, chromatography, and the predictive power provided by simulations. In addition, by developing a peer-coaching relationship with new faculty, undergraduate instruction in analytical chemistry at VCU is being enhanced.This project focuses on the following three specific aims: (1) design, construction, and characterization of liquid chromatography columns with a continuous gradient in chemical functionality along their length, (2) development and implementation of tools to predict the chromatographic responses for various sets of analytes on a continuous gradient stationary phase, and (3) coupling simulations with experiments to determine what gradient lengths and compositions are needed to obtain optimum separations, thus avoiding the trial and error approach usually used in method development. For proof-of-principle, silica monolithic columns and columns packed with superficially porous particles are strategically modified to incorporate a continuous gradient in C8, C18, amine, and/or phenyl groups using silane chemistry and controlled rate infusion (CRI), a method recently developed in the Collinson group. The integration of the Collinson group's expertise in sol-gel chemistry and surface chemical gradients with the Rutan group's expertise in modeling of separations and liquid chromatography is leading to the development of new methodologies for problems of societal relevance, ranging from biomarker discovery to detection of low levels of environmental contaminants.