Cameron Schwartz Thesis 7_12_21.pdf (1.89 MB)

DEVELOPMENT OF NOVEL LIQUID CHROMATOGRAPHY STATIONARY PHASES FOR IMPROVED CHARACTERIZATION OF BIOPHARMACEUTICALS

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thesis
posted on 30.07.2021, 15:11 by Cameron C SchwartzCameron C Schwartz
Monoclonal antibodies are large, complex biomolecules that can be difficult to characterize. Characterization is important because of the various post translational modifications that can occur during manufacturing, processing, and storage. Some modifications can lead to efficacy and safety issues and therefore are heavily monitored. A leading way to monitor various modifications is by using liquid chromatography. The high sensitivity, reproducibility, and ability to quantitate analytes makes it very attractive for monoclonal antibody characterization. The large molecular size of monoclonal antibodies (150 kDa) makes them challenging to separate efficiently and with high enough resolution to be helpful. New column technologies that would help improve protein separation efficiencies and slectivities would greatly help in this challenging process. In this thesis, three novel bonded phases are developed for the separation of monoclonal antibodies including a weak anion and cation exchanger (WAX, CEX) for the separation of charged species as well as a novel hydrophilic interaction chromatography (HILIC) for the separation of glycoforms. Column develop is achieved by optimizing selectivity and improving efficiency of separations by altering particle surface chemistry.

History

Degree Type

Doctor of Philosophy

Department

Chemistry

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Mary Wirth

Additional Committee Member 2

Corey Thompson

Additional Committee Member 3

Hilkka L Kenttämaa

Additional Committee Member 4

Jesse Zhang