High-Productivity Membrane Adsorbers: Polymer Surface-Modification Studies for Ion-Exchange and Affinity Bioseparations.
Degree: PhD, Chemical Engineering, 2014, Clemson University
This Dissertation centers on the surface-modification of macroporous membranes to make them selective adsorbers for different proteins, and the analysis of the performance of these membranes relative to existing technology. Traditional chromatographic separations for the isolation and purification of proteins implement a column packed with resin beads or gel media that contain specific binding ligands on their exposed surface area. The productivity of this process is balanced by the effective use of the binding sites within the column and the speed at which the separation can take place, in addition to the need to maintain sufficient protein purity and bioactivity. Because of the nature of the densely packed columns and, in the case of resin columns, the limited access to the binding sites internally located within the resin, the operating speed of this separation process may be constrained by mass-transfer and pressure limitations. Other constraints include the time-intensive measures taken to properly pack the columns, and the challenges associated with scaling chromatography columns to industrial-sized processes. Because of the excellent selectivity, chromatography processes are the workhorse for biopharmaceuticals drugs, and other plant- and animal- based protein products. Thus, there are many markets that could benefit by improvements to this technology. My strategy focused on modifying porous membranes with surface-initiated atom transfer radical polymerization (ATRP) to grow polymer chains containing functional groups that target three different protein-ligand interactions for three different types of chromatography: cation-exchange, carbohydrate affinity, and Arginine-specific affinity chromatography. Although each of these types of separation has different challenges and different possibilities for impact among their unique applications, they all have the common need for a stationary phase platform with the potential for fast separations and specific interactions. The common approach used in these studies, which is using membrane technology for chromatographic applications and using ATRP as a surface modification technique, will be introduced and supported by a brief review in Chapter 1. The specific approaches to address the unique challenges and motivations of each study system are given in the introduction sections of the respective Dissertation chapters. Chapter 2 describes my work to develop cation-exchange membranes. I discuss the polymer growth kinetics and characterization of the membrane surface. I also present an analysis of productivity, which measures the mass of protein that can bind to the stationary phase per volume of stationary phase adsorbing material per time. Surprisingly and despite its importance, this performance measure was not described in previous literature. Because of the significantly shorter residence time necessary for binding to occur, the productivity of these cation-exchange membrane adsorbers (300 mg/mL/min) is nearly two orders of magnitude higher than the productivity…
Advisors/Committee Members: Dr. Scott M. Husson, Dr. Charles Gooding, Dr. Douglas E. Hirt, Dr. Igor Luzinov.
Subjects/Keywords: arginine affinity; biotherapeutics; chromatography; concanavalin A; membrane adsorber; protein purfication; Chemical Engineering; Materials Science and Engineering; Polymer Science
…al., 2011). In this process, a CEX membrane adsorber is used in
bind-and-elute mode… …adsorber and
120 mg/L in single-membrane measurements with solution residence times of merely 35… …my
studies not only as an expert in the field of membrane science and surface modification… …1
1.1. Membrane chromatography for protein purification… …55
Table of Contents (Continued)
3. MEMBRANE ADSORBERS COMPRISING GRAFTED…
to Zotero / EndNote / Reference
APA (6th Edition):
Chenette, H. (2014). High-Productivity Membrane Adsorbers: Polymer Surface-Modification Studies for Ion-Exchange and Affinity Bioseparations. (Doctoral Dissertation). Clemson University. Retrieved from https://tigerprints.clemson.edu/all_dissertations/1319
Chicago Manual of Style (16th Edition):
Chenette, Heather. “High-Productivity Membrane Adsorbers: Polymer Surface-Modification Studies for Ion-Exchange and Affinity Bioseparations.” 2014. Doctoral Dissertation, Clemson University. Accessed November 27, 2020.
MLA Handbook (7th Edition):
Chenette, Heather. “High-Productivity Membrane Adsorbers: Polymer Surface-Modification Studies for Ion-Exchange and Affinity Bioseparations.” 2014. Web. 27 Nov 2020.
Chenette H. High-Productivity Membrane Adsorbers: Polymer Surface-Modification Studies for Ion-Exchange and Affinity Bioseparations. [Internet] [Doctoral dissertation]. Clemson University; 2014. [cited 2020 Nov 27].
Available from: https://tigerprints.clemson.edu/all_dissertations/1319.
Council of Science Editors:
Chenette H. High-Productivity Membrane Adsorbers: Polymer Surface-Modification Studies for Ion-Exchange and Affinity Bioseparations. [Doctoral Dissertation]. Clemson University; 2014. Available from: https://tigerprints.clemson.edu/all_dissertations/1319