Performance Characteristics of Charged Ultrafiltration Membranes: Fundamental Studies and Applications
Open Access
- Author:
- Mehta, Amit
- Graduate Program:
- Chemical Engineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 06, 2006
- Committee Members:
- Andrew Zydney, Committee Chair/Co-Chair
Wayne Roger Curtis, Committee Member
Darrell Velegol, Committee Member
Andrew Ewing, Committee Member - Keywords:
- Biotechnology
Bioseparation
Ultrafiltration
Protein Purification
Charged Membrane
Permeability
Selectivity
Bioprocessing - Abstract:
- Ultrafiltration is used extensively in the biotechnology and food industries for protein concentration and buffer exchange. Although several recent studies have demonstrated the importance of electrostatic interactions in ultrafiltration, there is little data available on the role of the nature and the number of charge groups on the overall membrane performance characteristics. The overall objective of this thesis was to develop a more quantitative understanding of the effects of the membrane surface charge density, the nature of the functional charge groups, and the spacer arm length on protein transport and fluid flow during ultrafiltration. Electrically-charged ultrafiltration membranes were generated by chemical modification of commercially-available composite regenerated cellulose membranes using a variety of chemistries. A new framework was developed to analyze the performance characteristics of the different ultrafiltration membranes, analogous to the “Robeson Plot” used to analyze the performance of gas separation membranes. This framework captures the inherent trade-off between hydraulic permeability and membrane selectivity, providing a quantitative method for evaluating the performance of ultrafiltration membranes. The effects of membrane surface charge density on protein transport, hydraulic permeability, and separation of binary protein mixtures was studied using a series of surface-modified cellulose membranes, with the charge density controlled by varying the extent of addition of a quaternary amine functionality. The transmission of positively charged cytochrome c decreased by a factor of 100 as the membrane zeta potential was increased from 0.3 to 6.6 mV due to the strong electrostatic exclusion of the like-charged protein. The protein sieving data were in good agreement with a partitioning model accounting for electrostatic effects, while the hydraulic permeability data were consistent with a flow model accounting for the effects of counter-electroosmosis. These electrically-charged membranes also provided very high resolution for the separation of myoglobin and lysozyme. High selectivity could be achieved with moderately charged membranes by using very low ionic strength solutions, while the more heavily charged membranes provided high selectivity up to salt concentrations of 40 mM. These results clearly demonstrate the potential of using membrane charge to design effective protein purification processes. Limited data obtained with a commercially relevant feedstock showed that these charged membranes could be used to significantly reduce the concentration of host cell proteins in the purification of a monoclonal antibody product. A variety of novel ultrafiltration membranes were synthesized with multiple charge groups along the spacer arm. These membranes provide very high performance characteristics. In addition, the results provide important insights into the affects of the spacer arm length and the nature of the functional group on protein transmission and fluid flow. These results not only demonstrate the capabilities of electrically-charged ultrafiltration membranes for bioprocessing applications, they also suggest a variety of strategies for the development of new classes of charged membranes with greatly enhanced performance.