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Biomolecular Transport Through Hemofiltration Membranes

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Abstract

A theoretical model for filtration of large solutes through a pore in the presence of transmembrane pressures, applied/induced electric fields, and dissimilar interactions at the pore entrance and exit is developed to characterize and predict the experimental performance of a hemofiltration membrane with nanometer scale pores designed for a proposed implantable Renal Assist Device (RAD). The model reveals that the sieving characteristics of the membrane can be improved by applying an external electric field, and ensuring a smaller ratio of the pore-feed and pore-permeate equilibrium partitioning coefficients when diffusion is present. The model is then customized to study the sieving characteristics for both charged and uncharged solutes in the slit-shaped nanopores of the hemofiltration device for the RAD. The effect of streaming potential or induced fields are found to be negligible under representative operating conditions. Experimental data on the sieving coefficient of bovine serum albumin, carbonic anhydrase and thyroglobulin are reported and compared with the theoretical predictions. Both steric and electrostatic partitioning are considered and the comparison suggests that in general electrostatic effects are present in the filtration of proteins though some data, particularly those recorded in a strongly hypertonic solution (10× PBS), show better agreement with the steric partitioning theory.

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References

  1. A.N. Asanov, L.J. Delucas, P.B. Oldham, and W.W. Wilson. Heteroenergetics of Bovine Serum Albumin Adsorption from Good Solvents Related to Crystallization Conditions. J. Colloid Interf. Sci., 191(1):222–235, 1997.

    Article  CAS  Google Scholar 

  2. R.E. Baltus and J.L. Anderson. Hindered diffusion of asphaltenes through microporous membranes. Chemical engineering science, 38(12):1959–1969, 1983.

    Article  CAS  Google Scholar 

  3. B. Bloth and R. Bergquis. The ultrastructure of human thyroglobulin. Journal of Experimental Medicine, 128(5):1129–1136, 1968.

    Article  PubMed  CAS  Google Scholar 

  4. J.A. Brant and A.E. Childress. Membrane-Colloid Interactions: Comparison of Extended DLVO Predictions with AFM Force Measurements. Environmental Engineering Science, 19(6):413–427, 2002.

    Article  CAS  Google Scholar 

  5. J.L. Brash and S. Uniyal. Dependence of albumin-fibrinogen simple and competitive adsorption on surface properties of biomaterials. J Polym Sci, 66:377–389, 1979.

    CAS  Google Scholar 

  6. H. Brenner and L.J. Gaydos. The constrained Brownian movement of spherical particles in cylindrical pores of comparable radius. J. Colloid Interface Sci, 58(2):312–356, 1977.

    Article  Google Scholar 

  7. Chen, L., and A. T. Conlisk. Effect of nonuniform surface potential on electroosmotic flow at large applied electric field strength. Biomed. Microdevices 11(1):173–181, 2009.

    Google Scholar 

  8. Cussler, E. L. Diffusion: Mass Transfer in Fluid Systems. Cambridge University Press, 1997.

  9. P. Dechadilok and W.M. Deen. Hindrance Factors for Diffusion and Convection in Pores. Ind. Eng. Chem. Res, 45(21):6953–6959, 2006.

    Article  CAS  Google Scholar 

  10. W.M. Deen. Hindered transport of large molecules in liquid-filled pores. American Institue of Chemical Engineers Journal, 33(9):1409–1422, 1987.

    CAS  Google Scholar 

  11. W.M. Deen, B. Satvat, and J.M. Jamieson. Theoretical model for glomerular filtration of charged solutes. American Journal of Physiology- Renal Physiology, 238(2):126–139, 1980.

    Google Scholar 

  12. W.M. Deen, M.J. Lazzara, and B.D. Myers. Structural determinants of glomerular permeability. Am J Physiol Renal Physiol, 281:579–596, 2001.

    Google Scholar 

  13. V. Deshpande and S.G. Venkatesh. Thyroglobulin, the prothyroid hormone: chemistry, synthesis and degradation. Biochimica et Biophysica Acta (BBA)/Protein Struct. Mol. Enzymol. 1430(2):157–178, 1999.

    Article  CAS  Google Scholar 

  14. Elimelech, M. Particle Deposition and Aggregation: Measurement, Modelling and Simulation. Butterworth-Heinemann, 1998.

  15. W.H. Fissell and H.D. Humes. Tissue engineering renal replacement therapy. In J. D. Bronzino, editor, Tissue Engineering and Artificial Organs, pages 60-1-60-14. CRC Press, Boca Raton, Florida, 2006.

    Google Scholar 

  16. Fissell, W. H., H. D. Humes, S. Roy, and A. Fleischman. Ultrafiltration membrane, device, bioartificial organ, and methods, May 23 2006. US Patent 7,048,856.

  17. Fissell, W. H., A. Dubnisheva, A. N. Eldridge, A. J. Fleischman, A. L. Zydney, and S. Roy. High-performance silicon nanopore hemofiltration membranes. J. Membrane Sci. 326(1):58–63, 2009.

    Google Scholar 

  18. W.H. Fissell, S. Manley, A. Dubnisheva, J. Glass, J. Magistrelli, A.N. Eldridge, A.J. Fleischman, A.L. Zydney, and S. Roy. Ficoll is not a rigid sphere. American Journal of Physiology- Renal Physiology, 293(4):F1209–F1213, 2007.

    Article  PubMed  CAS  Google Scholar 

  19. P. Ganatos, R. Pfeffer, and S. Weinbaum. A strong interaction theory for the creeping motion of a sphere between plane parallel boundaries. Part 2. Parallel motion. Journal of Fluid Mechanics Digital Archive, 99(04):755–783, 2006.

    Google Scholar 

  20. Gao, J., F. A. Gomez, R. Harter, and G. M. Whitesides. Determination of the effective charge of a protein in solution by capillary electrophoresis. Proc. Natl. Acad. Sci. USA 91(25):12027, 1994.

    Google Scholar 

  21. J.S. Green and J.W. Jorgenson. Minimizing adsorption of proteins on fused silica in capillary zone electrophoresis by the addition of alkali metal salts to the buffers. J. Chromatogr, 478(1):63–70, 1989.

    Article  CAS  Google Scholar 

  22. X.M. He and D.C. Carter. Atomic structure and chemistry of human serum albumin. Nature, 358(6383):209–215, 1992.

    Article  PubMed  CAS  Google Scholar 

  23. R. Hogg, T.W. Healy, and D.W. Fuerstenau. Mutual coagulation of colloidal dispersions. Transactions of the Faraday Society, 62:1638–1651, 1966.

    Article  CAS  Google Scholar 

  24. H.D. Humes, W.H. Fissell, and K. Tiranathanagul. The future of hemodialysis membranes. Kidney International, 69:1115–1119, 2006.

    Article  PubMed  CAS  Google Scholar 

  25. K.L. Jones and C.R. O’Melia. Protein and humic acid adsorption onto hydrophilic membrane surfaces: effects of pH and ionic strength. Journal of Membrane Science, 165(1):31–46, 2000.

    Article  CAS  Google Scholar 

  26. M. Karlsson, L.G. Martensson, B.H. Jonsson, and U. Carlsson. Adsorption of Human Carbonic Anhydrase II Variants to Silica Nanoparticles Occur Stepwise: Binding Is Followed by Successive Conformational Changes to a Molten-Globule-like State. Langmuir, 16(22):8470–8479, 2000.

    Article  CAS  Google Scholar 

  27. B.J. Kirby and E.F. Hasselbrink. Zeta potential of microfluidic substrates: 1. Theory, experimental techniques, and effects on separations. Electrophoresis, 25(2):187–202, 2004.

    Article  PubMed  CAS  Google Scholar 

  28. R. Kurrat, J.E. Prenosil, and J.J. Ramsden. Kinetics of Human and Bovine Serum Albumin Adsorption at Silica–Titania Surfaces. Journal of Colloid And Interface Science, 185(1):1–8, 1997.

    Article  CAS  Google Scholar 

  29. M.J. Lazzara, D. Blankschtein, and W.M. Deen. Effects of Multisolute Steric Interactions on Membrane Partition Coefficients. Journal of Colloid And Interface Science, 226(1):112–122, 2000.

    Article  CAS  Google Scholar 

  30. M.J. Lazzara and W.M. Deen. Effects of plasma proteins on sieving of tracer macromolecules in glomerular basement membrane. American Journal of Physiology- Renal Physiology, 281(5):860–868, 2001.

    Google Scholar 

  31. Lazzara MJ, Deen WM. (2004) Effects of concentration on the partitioning of macromolecule mixtures in agarose gels. Journal of Colloid And Interface Science 272(2):288–297

    Article  CAS  Google Scholar 

  32. S. Levine, J.R. Marriott, G. Neale, and N. Epstein. Theory of electrokinetic flow in fine cylindrical capillaries at high zeta-potentials. J. Colloid Interface Sci, 52(1):136–149, 1975.

    Article  Google Scholar 

  33. C.A. Lopez, D.G. Attiah, A.J. Fleischman, S. Roy, and T.A. Desai. Evaluation of silicon-based micro- and nanostructured environments on neurosecretory cells. Biomaterials, 27:3075, 2006.

    Article  PubMed  CAS  Google Scholar 

  34. Martini, F. Fundamentals of Anatomy and Physiology, 5th edn. Prentice Hall International Inc., 2001.

  35. S. Matsubara, K. Okabe, K. Ouchi, Y. Miyazaki, Y. Yajima, H. Suzuki, M. Otsuki, and S. Matsuno. Continuous removal of middle molecules by hemofiltration in patients with acute liver failure. Critical Care Medicine, 18(12):1331, 1990.

    Article  PubMed  CAS  Google Scholar 

  36. A. Mehta and A.L. Zydney. Permeability and selectivity analysis for ultrafiltration membranes. Journal of Membrane Science, 249(1-2):245–249, 2005.

    Article  CAS  Google Scholar 

  37. R. Michel, S. Pasche, M. Textor, and D.G. Castner. Influence of PEG architecture on protein adsorption and conformation. Langmuir, 21(26):12327–12332, 2005.

    Article  PubMed  CAS  Google Scholar 

  38. J.Y. Min, D. Kim, and S.J. Kim. A novel approach to analysis of electroosmotic pumping through rectangular-shaped microchannels. Sensors & Actuators: B. Chemical, 120(1):305–312, 2006.

    Article  Google Scholar 

  39. H. Ohshima and T. Kondo. Electrostatic interaction of an ion-penetrable sphere with a hard plate: contribution of image interaction. Journal of colloid and interface science, 157(2):504–508, 1993.

    Article  CAS  Google Scholar 

  40. A. Papra, N. Gadegaard, and N.B. Larsen. Characterization of Ultrathin Poly (ethylene glycol) Monolayers on Silicon Substrates. LANGMUIR, 17(5):1457–1460, 2001.

    Article  CAS  Google Scholar 

  41. N.A. Patankar and H.H. Hu. Numerical Simulation of Electroosmotic Flow. Sens. Actuators, B, 20:103–110, 1994.

    Article  Google Scholar 

  42. Peters, T. All About Albumin: Biochemistry, Genetics and Medical Applications. Academic Press, Inc., 1996.

  43. N.S. Pujar and A.L. Zydney. Electrostatic and Electrokinetic Interactions during Protein Transport through Narrow Pore Membranes. Industrial & Engineering Chemistry Research, 33(10):2473–2482, 1994.

    Article  CAS  Google Scholar 

  44. N.S. Pujar and A.L. Zydney. Charge Regulation and Electrostatic Interactions for a Spherical Particle in a Cylindrical Pore. Journal of Colloid And Interface Science, 192(2):338–349, 1997.

    Article  CAS  Google Scholar 

  45. N.S. Pujar and A.L. Zydney. Electrostatic effects on protein partitioning in size-exclusion chromatography and membrane ultrafiltration. J. Chromatogr. A, 796:229–238, 1998.

    Article  PubMed  CAS  Google Scholar 

  46. Roy, S. and W. H. Fissell, 2008 (Private communication).

  47. R. Scherrer and P. Gerhardt. Molecular sieving by the Bacillus megaterium cell wall and protoplast. J Bacteriol, 107(3):718–735, 1971.

    PubMed  CAS  Google Scholar 

  48. F.G. Smith and W.M. Deen. Electrostatic double-layer interactions for spherical colloids in cylindrical pores. J Coll Interface Sci, 78:444–465, 1980.

    Article  CAS  Google Scholar 

  49. J.T. Smith and Z. El Rassi. Capillary Zone Electrophoresis of Biological Substances with Surface-Modified Fused Silica Capillaries with Switchable Electroosmotic Flow. J. High Resolut. Chromatogr, 15(9):573–578, 1992.

    Article  CAS  Google Scholar 

  50. C.C. Striemer, T.R. Gaborski, J.L. Mcgrath, and P.M. Fauchet. Charge-and size-based separation of macromolecules using ultrathin silicon membranes. Nature(London), 445(7129):749–753, 2007.

    Article  CAS  Google Scholar 

  51. D. Venturoli and B. Rippe. Ficoll and dextran vs. globular proteins as probes for testing glomerular permselectivity: effects of molecular size, shape, charge, and deformability. American Journal of Physiology- Renal Physiology, 288(4):605–613, 2005.

    Article  Google Scholar 

  52. Yan ZY, Acrivos A, Weinbaum S (2006) Fluid skimming and particle entrainment into a small circular side pore. Journal of Fluid Mechanics Digital Archive 229:1–27

    Google Scholar 

  53. Zeman, L. J. and A. L. Zydney. Microfiltration and Ultrafiltration: Principles and Applications. CRC Press, 1996.

  54. M. Zhang and M. Ferrari. Hemocompatible Polyethylene Glycol Films on Silicon. Biomedical Microdevices, 1(1):81–89, 1998.

    Article  CAS  Google Scholar 

  55. B.V. Zhmud, A. Meurk, and L. Bergström. Evaluation of Surface Ionization Parameters from AFM Data. Journal of Colloid And Interface Science, 207(2):332–343, 1998.

    Article  CAS  Google Scholar 

  56. A.L. Zydney and N.S. Pujar. Protein transport through porous membranes: effects of colloidal interactions. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 138(2-3):133–143, 1998.

    Article  CAS  Google Scholar 

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Acknowledgments

The project described was supported by NIH Grant Number R01EB008049 from the National Institute of Biomedical Imaging and Bioengineering. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Biomedical Imaging and Bioengineering or the National Institutes of Health. The authors thank Prof. Andrew L. Zydney (AZ) of Pennsylvania State University for reviewing the manuscript and for helpful suggestions. The writing and model development for this paper was principally undertaken by SD under guidance from TC and additional guidance from SR and AZ; the experimental results were contributed by WHF and SR.

Cleveland Clinic Disclosure Policy

Co-authors, WHF and SR, are inventors on one or more patents related to the subject material in this paper, and are entitled to a share of any royalty payments that may derive from commercialization of the patent(s).

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Authors and Affiliations

  1. Department of Mechanical Engineering, The Ohio State University, 201 West 19th Avenue, Columbus, OH, 43210, USA

    A. T. Conlisk & Subhra Datta

  2. Departments of Nephrology and Hypertension and Biomedical Engineering, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    William H. Fissell

  3. Department of Biomedical Engineering, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Shuvo Roy

  4. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, 94158, USA

    Shuvo Roy

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  1. A. T. Conlisk
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  2. Subhra Datta
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  4. Shuvo Roy
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Correspondence to Subhra Datta.

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Conlisk, A.T., Datta, S., Fissell, W.H. et al. Biomolecular Transport Through Hemofiltration Membranes. Ann Biomed Eng 37, 722–736 (2009). https://doi.org/10.1007/s10439-009-9642-0

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  • DOI: https://doi.org/10.1007/s10439-009-9642-0

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