SBIR-STTR Award

The purification of large biomolecules is an important component of biological research and for the production of recombinant proteins that are being utilized for numerous applications in medicine. The conventional chromatographic media used for this purpose have large (greater than 5 nanometer) pores to accommodate these large molecules. As a consequence these media are extremely fragile and compressive, making their use in column chromatography and bioprocessing very difficult. Furthermore, in order to minimize the compressive pressure drops produced by buffer flow, the particle size of the media need to be large, typically more than 100 micrometers in diameter. The large size and the extremely small diffusion coefficients of large molecules within the pores of the particles, greatly reduces the efficiency of the separation processes. The goal of this project is focused on the development of a new type of chromatographic medium which can be prepared by applying very thin polymeric coatings (less than 6 micrometers) onto non-woven fabrics and having ion exchange groups that are suitable for the adsorption of large biomolecules. The resulting chromatographic media will have the desired combination of high efficiency and robustness, making their use as chromatographic media more effective, more efficient, and at lower cost than existing media for similar applications. The specific aims are (1) develop a family of non-wovens with polyurea coatings having ion exchange functionalities, high capacities, and high rates of mass transfer for recombinant proteins, monoclonal antibodies, and smaller proteins, (2) characterize the coated non-wovens in terms of their capacities, kinetics, and diffusivities for biomolecules using flow through devices, and (3) develop designs and build prototypes for chromatographic devices based on the properties of the coated non-wovens.

Thesaurus Terms:
ion exchange chromatography, material, molecular size, protein purification, technology /technique development adsorption, antibody, biomedical equipment development, chemical kinetics, diffusion, monoclonal antibody, polymer, recombinant protein, surface coating

This project is focused on the development of a new type of chromatographic medium prepared by applying very thin polymeric coatings onto non-woven fabrics and having ion exchange groups suitable for adsorption and purification of large biomolecules. The resulting chromatographic media and devices will have a combination of high efficiency and robustness, making their use more effective, more efficient, and at lower cost than existing media for similar applications. The specific aims are to (1) optimize and develop chemistries for a family of coated non-wovens having ion exchange functionalities, (2) develop and demonstrate the performance of the coating process using an apparatus for continuous coating of non-woven sheet stock, (3) characterize substrates for applications to recombinant proteins, (4) build prototype devices based on the properties of the coated non-wovens and characterize performance. Purification of large biomolecules is an important component of biological research and for the production of recombinant proteins utilized for numerous applications in medicine. Conventional chromatographic media for this purpose have large pores to accommodate these large molecules. As a consequence, they are fragile and compressive making their use in column chromatography and bioprocessing difficult. Also, to minimize the compressive pressure drops produced by buffer flow, the particle size of the media need to be large (50-100 ? dia.). The large particle size and small diffusion coefficients of large molecules within the particle pores reduces efficiency of the separation process. Potential innovations of this project address the inherent problems with existing technology. This research will result in new, low cost materials and technology for purification and isolation of recombinant proteins and large biomolecules. Potential commercial applications of this project are (a) coated non-woven materials for anion and cation exchange chromatography, (b) coated non-woven materials for affinity chromatography, (c) low cost, disposable devices for scale-up chromatography, and (d) application specific licenses to companies involved in membrane products. The relevance of the proposed research to public heath is for the accelerated and improved development of therapeutic drugs that are being developed to eliminate suffering and death due to cancer. The technology...from this project is needed to ensure delivery and reduce the cost of new, anti-cancer therapeutics such as recombinant proteins which are needed in large quantities