Projects / Programmes
Structural and surface properties of fibrous membranes for purification and chromatographic separation of biomacromolecules
| Code |
Science |
Field |
Subfield |
| 2.14.01 |
Engineering sciences and technologies |
Textile and leather |
Textile and technical fibres |
| Code |
Science |
Field |
| T470 |
Technological sciences |
Textiles technology |
| Code |
Science |
Field |
| 2.05 |
Engineering and Technology |
Materials engineering |
Fibers and polymers, Plasma technology, Engineering, Filters, Membranes, Morphology, Surface chemistry, Purification, Separation, Chromatography.
Researchers (15)
Organisations (4)
Abstract
Current trends in the purification of biopharmaceuticalsare driven by higher productivity, lower cost of production and increased development speed, while achieving strict regulation requirements related to the purity levelsin final formulations.This may be accomplished by either reducing product doses or increasing production scale. Another trend is the increased use of disposable systemsor single-use membranes, which eliminate the need for the development and validation of cleaning cycles. Membrane technologieshave, thus, become essential in current downstream processes, starting with the complete and sterile bacteria filtration, followed by separation of the cells to capture and concentrate the products, and continued with the removal of impurities during the polishing steps using chromatography. The critical step in a profitable purificationis to carry out separation in a highly efficient manner, (with low energy consumption and minimal throughput time), safely and reliably.
In this project, we aimto investigate the preparation/manufacturing process for developing of novel low-cost and high-flow fiber-based filters and ion-exchange membranes,which may act as a complementary methodto the existing polymeric-based filtersor expensive chromatographic CIM monolithic cartridge-based systems,to enable: i) High and sterile bacteria filtration retention, ii) Efficient gDNA and endotoxin removal, and iii) Chromatographic purification/separations of proteins, with high performance and economic feasibility.
The membranes will be prepared by merging existing textile, paper and composite technologiesoptionally in a combination withadvanced plasma processing,to modify or functionalize the fibers` surface further chemically with a specific ligand, and, thus, to tailor/increase the membrane surface area and mass transfer properties with good binding capacity, supporting efficient biomolecules` purification, separation and recovery.
The most important challenge, being also a synergistic key point,will be to create differently nano-to-micro vs. micro-to-macro sized and inter-connective porous materials of various surface/interface properties (charge, hydrophobicity), and, thus, to adjust the membrane manufacturing process with the final application requirements (i.e. good pressure/pH/sterilization stability, small/no swelling/shrinking and good/high permeation flow, accomplished withgood filtration/separation performancein terms of retention and permeability).
In order to understand the filtration and chromatographic performanceof the created membranes, several parameters will be addressed, including the starting materials before and after their modification, up to evaluation of basic membrane properties, such as morphology (pore size and geometry, pore size distribution and inter-connectivity, surface area,density), mechanical strength and compression vs. stress-strain stability, physico-chemical properties (thickness, surface charge type/quantity and distribution, hydrophobicity, swelling/sorption and shrinking behavior under different pH, ionic strength), molecular weight cut-off definition, permeability vs. binding capacity and recovery, as well as sterilization, cleanability and reusing, by using relevant analytical techniques and colloidal filtration/separation theoretical principles.
This will be the most important impact on the results, and, as such, through the proof-of-concept principle (reaching TRL3),will contribute greatly to the technical knowledge in that field, covering also textile, material, technical, and chemistry sciences, as well as filtration and separation processes. In addition, the knowledge generated can be used to develop specific fibrous structures for manyother applications,such as water reuse (cleantech) applications, beverage processing, and air filtration.A strengthening of research cooperation between all involved groups is expected to continue further under European or other inter/national programmes.
Significance for science
With a burgeoning biotechnology market, there is an ongoing search for new and improved purification methods in an effort to lower costs and improve yields, while maintaining high product purity. Several promising alternatives have been described in the literature, such as affinity precipitation, high-performance tangential flow filtration, filtration strategies based on affinity interactions, electrophoresis, etc.Among them, filtration with ion-exchange membranes as substitutes for flow-through chromatography in multi-polishing steps, represents a highly complementary alternative in the removal of larger biomolecular impurities with increased flow rates, reduced buffer consumption and time. In addition, the use of such membranes is still not well established, mainly because of the conservative nature of the industry in adopting new technologies, although it may allow new innovations in the fields of Gene Therapies, Regenerative Medicine, Cell Therapies and other medically relevant drugs.
Despite the orientation of the project into applicability, there are certain contents that are highly relevant scientifically. A clear basic and novel scientific contribution with high impact is envisaged through several well defined and structured experiments that would be designed to understand the basic structural, physicochemical and filtration/chromatographic features of new fiber-based filter membranes, their correlation under different application conditions, and further optimization for efficient, straightforward and cost-effective biotechnological applications – be compared to the existing filters and expensive CIM monoliths used in this area.Accordingly, all partners are expected to broaden their competences in matching industry needs towards new applications, resulting in higher standards and their promotion, not only within the national academic and technological programs, but also internationally, regarding the high possibility for publications in peer-reviewed journals with high impact factor and a high degree of citations, as well as communications within the scientific and business communities. Any of the inventions may be protected by a patent.
In addition, the knowledge generated can be used to develop specific fiber-based porous structures for many other applications, such as water reuse (cleantech) applications, beverage processing, and air filtration.Some general, socio-economical, and business impacts and aspects about the future use of textile fibers as the main raw-material are also obvious, bringing a high application impact to many Sloveniantextilecompanies.
Finally, the research cooperation between all the involved groups will be strengthening, and the basis of a network for future collaboration within the European FP, or other inter/national programs will be initiated - to intensify promotion not only within the national academic and technological frames, but also internationally.
Significance for the country
With a burgeoning biotechnology market, there is an ongoing search for new and improved purification methods in an effort to lower costs and improve yields, while maintaining high product purity. Several promising alternatives have been described in the literature, such as affinity precipitation, high-performance tangential flow filtration, filtration strategies based on affinity interactions, electrophoresis, etc.Among them, filtration with ion-exchange membranes as substitutes for flow-through chromatography in multi-polishing steps, represents a highly complementary alternative in the removal of larger biomolecular impurities with increased flow rates, reduced buffer consumption and time. In addition, the use of such membranes is still not well established, mainly because of the conservative nature of the industry in adopting new technologies, although it may allow new innovations in the fields of Gene Therapies, Regenerative Medicine, Cell Therapies and other medically relevant drugs.
Despite the orientation of the project into applicability, there are certain contents that are highly relevant scientifically. A clear basic and novel scientific contribution with high impact is envisaged through several well defined and structured experiments that would be designed to understand the basic structural, physicochemical and filtration/chromatographic features of new fiber-based filter membranes, their correlation under different application conditions, and further optimization for efficient, straightforward and cost-effective biotechnological applications – be compared to the existing filters and expensive CIM monoliths used in this area.Accordingly, all partners are expected to broaden their competences in matching industry needs towards new applications, resulting in higher standards and their promotion, not only within the national academic and technological programs, but also internationally, regarding the high possibility for publications in peer-reviewed journals with high impact factor and a high degree of citations, as well as communications within the scientific and business communities. Any of the inventions may be protected by a patent.
In addition, the knowledge generated can be used to develop specific fiber-based porous structures for many other applications, such as water reuse (cleantech) applications, beverage processing, and air filtration.Some general, socio-economical, and business impacts and aspects about the future use of textile fibers as the main raw-material are also obvious, bringing a high application impact to many Sloveniantextilecompanies.
Finally, the research cooperation between all the involved groups will be strengthening, and the basis of a network for future collaboration within the European FP, or other inter/national programs will be initiated - to intensify promotion not only within the national academic and technological frames, but also internationally.
Most important scientific results
Most important socioeconomically and culturally relevant results
Interim report
