Therapeutic antibody removal is performed to facilitate ABO-incompatible kidney transplants and heart and kidney xenotransplants, and to treat Goodpasture syndrome, myasthenia gravis, hemophilia with inhibitors, and thrombocytopenic purpura. Antibody removal is achieved non-selectively, via plasma exchange, or semi-selectively, via plasma perfusion through immunoadsorption columns containing immobilized protein A. We are developing hollow fiber-based specific antibody filters (SAFs) that selectively remove antibodies of a given specificity directly from whole blood, without separation of the plasma and cellular blood components and with minimal removal of plasma proteins other than the targeted antibodies. The working unit of the SAF is a hollow fiber dialysis membrane with antigens, specific for targeted antibodies, immobilized on the inner fiber wall. Several thousand SAF fibers are connected in parallel to produce a filter similar in construction to a hollow fiber hemodialyzer. A principal goal of our research is to identify the primary mechanisms that control antibody transport within the SAF, and to use this information to guide the choice of design and operational parameters that maximize the SAF-based antibody removal rate. We approached this goal by formulating a simple mathematical model of SAF-based antibody removal and performing in vitro antibody removal experiments to test key predictions of the model. Our model revealed three antibody transport regimes, defined by the magnitude of the Damköhler number Da (antibody-binding rate/antibody diffusion rate): reaction-limited (Da ≤ 0.1), intermediate (0.1 < Da < 10), and diffusion-limited (Da ≥ 10). For a given SAF geometry, blood flow rate, and antibody diffusivity, the highest antibody removal rate was predicted for diffusion-limited antibody transport. We performed in vitro antibody removal experiments in which SAFs containing immobilized bovine albumin (BSA) were used to remove anti-BSA antibodies from buffer. The measured anti-BSA removal rates were consistent with antibody transport in the intermediate regime. We concluded that initial SAF development work should focus on achieving diffusion-limited antibody transport by maximizing the SAF antibody-binding capacity. If diffusion-limited antibody transport is achieved, the antibody removal rate can be raised further by increasing the number and length of the SAF fibers and by increasing the blood flow rate through the SAF.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04152003-184800 |
| Date | 08 May 2003 |
| Creators | Hout, Mariah Sydney |
| Contributors | Alan J. Russell, Ph.D., William J. Federspiel, Ph.D., William R. Wagner, Ph.D., Adriana Zeevi, Ph.D. |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04152003-184800/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
Page generated in 0.0016 seconds