CAREER: Parallel Two-Dimensional Liquid Chromatography Utilizing Capillary Columns

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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.