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Theoretical and Experimental Analysis of Anti-A Antibody Capture in Novel Integrated Bead and Hollow Fiber Modules

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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.

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Acknowledgments

The work presented in this publication was made possible by Grant Number HL69956-01 from the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Heart, Lung, and Blood Institute or NIH. We would like to recognize the McGowan Institute for Regenerative Medicine for support on this study.

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Authors and Affiliations

  1. McGowan Institute for Regenerative Medicine, University of Pittsburgh, 215 McGowan Institute, 3025 East Carson Street, Pittsburgh, PA, 15203, USA

    Azadeh Alikhani & William J. Federspiel

  2. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15203, USA

    William J. Federspiel

  3. Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, 15203, USA

    Azadeh Alikhani & William J. Federspiel

  4. Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, 15203, USA

    William J. Federspiel

Authors
  1. Azadeh Alikhani
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  2. William J. Federspiel
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Correspondence to William J. Federspiel.

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Associate Editor Bahman Anvari oversaw the review of this article.

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Alikhani, A., Federspiel, W.J. Theoretical and Experimental Analysis of Anti-A Antibody Capture in Novel Integrated Bead and Hollow Fiber Modules. Ann Biomed Eng 39, 953–963 (2011). https://doi.org/10.1007/s10439-010-0233-x

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  • DOI: https://doi.org/10.1007/s10439-010-0233-x

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