CAREER: Parallel Two-Dimensional Liquid Chromatography Utilizing Capillary Columns

在化学系化学测量和成像项目的支持下，罗文大学的James Grinias博士将研究新的二维液相色谱（2D-LC）技术，用于测量小分子蛋白质材料的关键质量属性。由小分子和蛋白质组成的生物制药在制药工业中的重要性日益增加，因为它们有可能解决其他类型药物制剂的缺点。该行业的化学分析师需要新的测量工具来确保这些小分子蛋白质材料的含量和纯度。罗文大学的James Grinias博士使用液相色谱法来分离和测量含有活性药物成分和杂质的复杂混合物中的单个分子。该项目致力于创建一种二维液体分离技术，可以同时测量这种复杂混合物的多种属性，这有助于确保小分子蛋白质材料的纯度。一组来自多个行业的化学分离专家正在与Grinias博士合作，为工业环境中现代化学测量科学实验室所需的高价值技术技能提供反馈。一项新的推广计划通过使用远程学习策略向非传统学生教授这些关键技能，从而帮助他们在该领域获得职业。通过该奖项，化学测量和成像计划资助罗文大学的James Grinias博士研究用于测量小分子蛋白质材料关键质量属性的新型二维液相色谱（2D-LC）技术。目前在小分子蛋白材料中表征这些属性的策略需要多种不同的色谱方法和色谱柱，这可能是一个缓慢而艰巨的过程。Grinias博士通过使用平行2D-LC技术克服了这一问题，该技术利用二维的多个毛细管LC柱同时执行多种分离方法。这种方法增加了分析的吞吐量，减少了基于使用的小溶剂量而产生的化学废物的数量，并通过方法自动化的改进限制了分析人员处理样品的风险。该职业奖项目通过开发一种多泵、毛细管尺度系统，用于平行2D-LC、耦合吸光度和质谱检测，用于选择性通道监测，并展示了多属性方法的并行完成，从而建立了这项新技术。这些研究目标与一项教育计划相关联，该计划侧重于识别行业领导者的重要工作技能，并创建旨在教授这些技能的远程学习课程。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Dr. James Grinias at Rowan University will study new two-dimensional liquid chromatography (2D-LC) techniques used to measure critical quality attributes in small molecule-protein materials. Biopharmaceuticals composed of small molecules and proteins are increasing in importance within the pharmaceutical industry, because of their potential for addressing the shortcomings of other types of pharmaceutical agents. Chemical analysts within this industry need new measurement tools to ensure the content and purity of these small molecule-protein materials. Dr. James Grinias of Rowan University uses liquid chromatography to help separate and measure the individual molecules within complex mixtures that contain both active pharmaceutical ingredients and impurities. This project focuses on the creation of a two-dimensional liquid separation technique that can simultaneously measure multiple attributes of such complex mixtures, which helps ensure the purity of small molecule-protein materials. A group of chemical separation experts from multiple industries are collaborating with Dr. Grinias to provide feedback on high-value technical skills that are required in modern chemical measurement science laboratories in industrial settings. A new outreach program teaches these critical skills to nontraditional students by use of remote learning strategies, thereby helping them obtain careers in this field. With this award, the Chemical Measurement and Imaging Program is funding Dr. James Grinias at Rowan University to study new two-dimensional liquid chromatography (2D-LC) techniques used to measure critical quality attributes in small molecule-protein materials. Current strategies for characterizing these attributes in small molecule-protein materials require multiple, different chromatographic methods and columns, which can be a slow and arduous process. Dr. Grinias is overcoming this issue through the use of a parallel 2D-LC technique that utilizes multiple capillary LC columns in the second dimension to simultaneously perform multiple separation methods. This approach increases the throughput of the analyses, reduces the amount of chemical waste that is generated based on the small solvent volumes used, and limits the risks of sample handling for analysts through improvements in method automation. This CAREER Award project establishes this new technique by developing a multi-pump, capillary-scale system for parallel 2D-LC, coupling absorbance and mass spectrometric detection for selective channel monitoring, and demonstrating the parallel completion of multi-attribute methodology. These research objectives are connected to an educational plan that focuses on the identification of important job skills by industry leaders and the creation of a remote learning curriculum designed to teach these skills.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.