Mathematical and Experimental Analyses of Antibody of Antibody Transprot in Hollow-Fiber-Based Specific Antibody Filters

摘要

We are devfeloping hollow fiber-based specific antibody filters(SAFs) that selectively remove antigodies of a given specificity directly from whole blood,without separation of rthe plasma and cellular blood components and with minimal removal of plasma proteins other than the targeted pathogenic antibodiese.A principal goal of our reserach 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 opertional parameters that maximize the SAF-based antbody removal rate.In this study,we formulated a simple mathematical model of SAF-based antibody removal and performed in vitro antibody removal experiments to tesk key predictions of the Damkohler number Da(characteristic antibody-binding rate/characteristic antibody diffusion rate):reacton-limited (Da<=0.1),intermediate(0.1=10).For a given SAF geometry,blood flow rate,and antibody diffusivity,the highest antibody removal rate was predicted for diffusion-limited antibody transport.Additionally,for diffusion-limited antibody transport the predicted antibody removal rate was independent of the antibody-binding rate and hence was the same for any antibody-antigen system and for any patient within one antibody-antigen system.Using SAF prototypes containign immoblized bovine serum albumin (BSA),we measured anti-BSA removal rates consistent with transport in the inermediate regime (Da approx 3).We concluded that initial SAF development work should focus on achieving diffusion-limited antibody transprot by maximizing the SAF antibhody-binding capactity (hence maximizing the characteristic antibody-binding rate).If diffusion-limited antibody transprot is achieved,the antihbody removal rate may be raised further by increasing the number and length of the SAF fibers and by increasing the blood flow rate through the SAF.