11/09/2022
By Danielle Fretwell

The Francis College of Engineering, Department of Chemical Engineering, invites you to attend a doctoral dissertation proposal defense by Caitlin Morris on, “Upstream Biomanufacturing Development from Media Optimization to Modeling to Process Analytical Technology - Utilizing microfluidic electrophoresis to analyze and quantify host cell proteins in CHO cell bioprocesses.”

Date: Nov. 21, 2022
Time: 11 a.m. to 1 p.m.
Location: UCC415

Adviser: Seongkyu Yoon, Professor, Chemical Engineering, University of Massachusetts Lowell

Committee Members:

  • Stephen T. Lam, Assistant Professor, Chemical Engineering, University of Massachusetts Lowell
  • Gulden Camci-Unal, Associate Professor, Chemical Engineering, University of Massachusetts Lowell
  • Walfre Franco, Assistant Professor, Biomedical Engineering, University of Massachusetts Lowell
  • Michael Borys, Senior Director, Global Upstream and Cell Line Development, Bristol Myers Squibb

Abstract:

Microfluidic electrophoresis is garnering attention in the biopharmaceutical industry as a unique method for analyzing and characterizing biological agents. Current applications of microfluidic electrophoresis have been applied to DNA, RNA, and protein analysis. In general, microfluidic electrophoresis has been applied to samples that have been previously purified by chromatography, filtration, or other methods. In addition, the protein analysis that has been performed with microfluidic electrophoresis has included either purified IgG samples or standard sample solutions such as bovine serum albumin (BSA) or beta Lactoglobulin A. However, it is proposed that microfluidic electrophoresis can be used to analyze unpurified protein samples removed from cell cultures. Specifically, microfluidic electrophoresis will be evaluated to analyze and characterize host cell proteins (HCPs) from Chinese hamster ovary (CHO) cells. HCPs are a process-related impurity derived from the metabolism of the host organism (in this case, CHO cells) that can elicit an immune response if they are not removed from a final drug product. Thus, the removal and characterization of HCPs throughout a biomanufacturing purification process is of paramount importance. The proposed project will be completed in two phases. In phase I, a method will be developed using the 2100 Bioanalyzer system (Agilent Technologies, Santa Clara, CA) and the associated high-sensitivity protein 250 kits. A full factorial design will analyze the effects of altering the pH of the sample being loaded and the reduction of the protein within the sample being loaded on the resulting electropherogram. A method that can produce a peak resolution of 1 or greater will be developed to ensure that clear separation of host cell proteins can be obtained and that the host cell proteins can be quantified using the same method. In phase II, a novel microfluidic chip will be printed using the stereolithography 3D printing service offered by UMass Lowell’s MakerSpace. A similar full factorial design will be applied to this microfluidic device to determine the optimal operating conditions (including sample conditions and operating conditions for electrophoresis, such as voltage used). The results of this proposal will be twofold: 1) method development for a commercially available product that has not previously been used for host cell protein analysis and 2) a novel microfluidic device and standard operating procedure for host cell protein analysis that will enable operator flexibility and lower upfront investment.