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会化学部化学测量与成像计划资助。化学分离的目的是通过利用物种在固定相和流动相之间表现出的相互作用程度的差异，将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替代方法。不是在分离过程中操纵流动相的组成，而是改变固定相的组成。固定相的渐变有许多优点，包括能够提高选择性、分离时间和检测混合物中的物种的能力。协作研究小组之间的协同作用加强了对不同的本科生和研究生在最先进的材料合成、层析和模拟提供的预测能力方面的培训。此外，通过与新教师发展同行辅导关系，VCU的分析化学本科教学正在得到加强。本项目专注于以下三个具体目标：(1)设计、建造和表征化学官能度沿长度连续梯度的液相色谱柱，(2)开发和实施工具来预测各种分析物在连续梯度固定相上的色谱响应，以及(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组成，从而避免方法开发中通常使用的反复尝试的方法。对于原理证明，硅胶整体柱和填充了表面多孔颗粒的柱被战略性地修改，以在C8、C18、胺和/或苯基中加入连续的梯度，使用硅烷化学和控制速率渗透(CRI)，这是Collinson小组最近开发的一种方法。柯林森集团在溶胶-凝胶化学和表面化学梯度方面的专业知识与Rutan集团在分离和液相色谱建模方面的专业知识相结合，正在为从生物标记物发现到低水平环境污染物检测的社会相关性问题开发新的方法。

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.