title: Theoretical and experimental analysis of anti-A antibody capture in novel integrated bead and hollow fiber modules.
abstract: Anti-A/B antibody removal from blood reduces the hyperacute rejection risk following ABO-incompatible transplantation. We are developing an integrated bead and fiber module (BSAF) that selectively removes anti-A from blood. In BSAF blood flows through the inner lumen of microfiltration fibers. Starling flow carries plasma from the inner fiber lumen to the beads in the shell compartment where antibodies bind to covalently attached antigens on the beads. In this study, we developed a mathematical model to guide the choice of key design and operational parameters for a clinical BSAF device. The model demonstrated that for a given flow rate and reservoir volume, antibody removal rate was dependent on the magnitude of a lumped parameter, k (L) m (B)/Q (s), that characterizes the ratio of antibody uptake rate by the beads to the Starling flow rate in the device. The highest antibody removal rate was predicted for the perfusion limited regime, when k (L) m (B)/Q (s) → 10; Once this maximum limit was obtained, any further increase in the antibody removal rate was only possible by increasing the flow rate. Key model predictions were validated in a series of experiments. The model was then used to conceptually design a BSAF capable of a clinically relevant rate of anti-A removal.
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, 3025 East Carson Street, Pittsburgh, PA 15203, USA.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Alikhani
authors.forename: William J
authors.initials: WJ
authors.lastname: Federspiel
mesh_terms: D000017:ABO Blood-Group System / Q000302:isolation & purification*; D000042:Absorption; D001672:Biocompatible Materials / Q000737:chemistry; D001781:Blood Component Removal / Q000295:instrumentation* / Q000379:methods*; D003198:Computer Simulation; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D007518:Isoantibodies / Q000097:blood* / Q000302:isolation & purification*; D008955:Models, Cardiovascular; D016062:Porosity; D014462:Ultrafiltration / Q000379:methods*
chemical_list: D000017:ABO Blood-Group System; D001672:Biocompatible Materials; D007518:Isoantibodies