Surface modification of polymeric membranes for low protein binding

  • Higuchi, Akon (Department of Chemical and Materials Engineering, National Central University) ;
  • Tamai, Miho (Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology) ;
  • Tagawa, Yoh-Ichi (Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology) ;
  • Chang, Yung (Department of Chemical Engineering, R&D Center for Membrane Technology, Chung Yuan Christian University) ;
  • Ling, Qing-Dong (Cathay Medical Research Institute, Cathay General Hospital)
  • Received : 2009.10.21
  • Accepted : 2009.12.14
  • Published : 2010.04.25


Surface modification of microfiltration and ultrafiltration membranes has been widely used to improve the protein adsorption resistance and permeation properties of hydrophobic membranes. Several surface modification methods for converting conventional membranes into low-protein-binding membranes are reviewed. They are categorized as either physical modification or chemical modification of the membrane surface. Physical modification of the membrane surface can be achieved by coating it with hydrophilic polymers, hydrophilic-hydrophobic copolymers, surfactants or proteins. Another method of physical modification is plasma treatment with gases. A hydrophilic membrane surface can be also generated during phase-inverted micro-separation during membrane formation, by blending hydrophilic or hydrophilic-hydrophobic polymers with a hydrophobic base membrane polymer. The most widely used method of chemical modification is surface grafting of a hydrophilic polymer by UV polymerization because it is the easiest method; the membranes are dipped into monomers with and without photo-initiators, then irradiated with UV. Plasma-induced polymerization of hydrophilic monomers on the surface is another popular method, and surface chemical reactions have also been developed by several researchers. Several important examples of physical and chemical modifications of membrane surfaces for low-protein-binding are summarized in this article.


  1. Barona, G.N.B., Cha, B.J. and Jung, B. (2007), "Negatively charged poly(vinylidene fluoride) microfiltration membranes by sulfonation", J. Membrane Sci., 290(1-2), 46-54.
  2. Belfer, S., Fainchtain, R., Purinson, Y. and Kedem, O. (2000), "Surface characterization by FTIR-ATR spectroscopy of polyethersulfone membranes-unmodified, modified and protein fouled", J. Membrane Sci., 172(1-2), 113-124.
  3. Branch, D.W., Wheeler, B.C., Brewer, G.J. and Leckband, D.E. (2001), "Long-term stability of grafted polyethylene glycol surfaces for use with microstamped substrates in neuronal cell culture", Biomaterials, 22, 1035-1047.
  4. Castilho, L.R., Deckwer, W.D. and Anspach, F.B. (2000), "Influence of matrix activation and polymer coating on the purification of human IgG with protein A affinity membranes", J. Membrane Sci., 172, 269-277.
  5. Chang, Y., Cheng, T.Y., Shih, Y.J., Lee, K.R. and Lai, J.Y. (2008a), "Biofouling-resistance expanded poly(tetrafluoroethylene) membrane with a hydrogel-like layer of surface-immobilized poly(ethylene glycol) methacrylate for human plasma protein repulsions", J. Membrane Sci., 323, 77-84.
  6. Chang, Y., Shih, Y.J., Ruaan, R.C., Higuchi, A., Chen, W.Y. and Lai, J.Y. (2008b), "Preparation of poly(vinylidene fluoride) microfiltration membrane with uniform surface-copolymerized poly(ethylene glycol) methacrylate and improvement of blood compatibility", J. Membrane Sci., 309, 165-174.
  7. Chen, H. and Belfort, G. (1999), "Surface modification of poly(ether sulfone) ultrafiltration membranes by lowtemperature plasma-induced graft polymerization", J. Appl. Polym. Sci., 72, 1699-1711.<1699::AID-APP6>3.0.CO;2-9
  8. Chiang, Y.C., Chang, Y., Higuchi, A., Chen, W.Y. and Ruaan, R.C. (2009), "Sulfobetaine grafted poly(vinylidene fluroride) ultrafiltration membranes exhibit excellent antifouling property", J. Membrane Sci., 339(1-2), 151- 159.
  9. Crassous, G., Harjanto, F., Mendjel, H., Sledz, J., Schue, F., Meyer, G. and Jozefowicz, M. (1985), "A new asymmetric membrane having blood compatibility", J. Membrane Sci., 22(2-3), 269-282.
  10. Dai, Z.W., Nie, F.Q. and Xu, Z.K. (2005), "Acrylonitrile-based copolymer membranes containing reactive groups: Fabrication dual-layer biomimetic membranes by the immobilization of biomacromolecules", J. Membrane Sci., 264(1-2), 20-26.
  11. Dai, Z.W., Wan, L.S. and Xu, Z.K. (2008), "Surface glycosylation of polyacrylonitrile ultrafiltration membrane to improve its anti-fouling performance", J. Membrane Sci., 325, 479-485.
  12. Fan, Z.F., Wang, Z., Sun, N., Wang, J. and Wang, S. (2008), "Performance improvement of polysulfone ultrafiltration membrane by blending with polyaniline nanofibers", J. Membrane Sci., 320(1-2), 363-371.
  13. Fang, B.H., Ling, Q.Y., Zhao, W.F., Ma, Y., Bai, P., Wei, Q., Li, H. and Zhao, C. (2009), "Modification of polyethersulfone membrane by grafting bovine serum albumin on the surface of polyethersulfone/ poly(acrylonitrile-co-acrylic acid) blended membrane", J. Membrane Sci., 329(1-2), 46-55.
  14. Feldman, K., Hahner, G., Spencer, N.D., Harder, P. and Grunze, M. (1999), "Probing resistance to protein adsorption of oligo(ethylene glycol)-terminated self-assembled monolayers by scanning force microscopy", J. Am. Chem. Soc., 121, 10134-10141.
  15. Feng, W., Zhu, S., Ishihara, K. and Brush, J.L. (2005), "Adsorption of fibrinogen and lysozyme on silicon grafted with poly(2-methacryloyloxyethyl phosphorylcholine) via surface-initiated atom transfer radical polymerization", Langmuir, 21, 5980-5987.
  16. Ghosh, R. and Cui, Z.F. (1998), "Fractionation of BSA and lysozyme using ultrafiltration: effect of pH and membrane pretreatment", J. Membrane Sci., 139, 17-28.
  17. Goda, T., Konno, T., Takai, M., Moro, T. and Ishihara, K. (2006), "Biomimetic phosphorylcholine polymer grafting from polydimethylsiloxane surface using photo-induced polymerization", Biomaterials, 27(30), 5151- 5160.
  18. Gu, J.S., Yu, H.Y., Huang, L., Tang, Z.Q., Li, W., Zhou, J., Yan, M.G. and Wei, X.Y. (2009), "Chain-length dependence of the antifouling characteristics of the glycopolymer-modified polypropylene membrane in an SMBR", J. Membrane Sci., 326, 145-152.
  19. Harder, P., Grunze, M., Dahint, R., Whitesides, G.M. and Laibinis, P.E. (1998), "Molecular conformation in oligo(ethylene glycol)-terminated self-assembled monolayers on gold and silver surfaces determines their ability to resist protein adsorption", J. Phys. Chem. B, 102, 426-436.
  20. Hatakeyama, E.S., Ju, H., Gabriel, C.J., Lohr, J.L., Bara, J.E., Noble, R.D., Freeman, B.D. and Gin, D.L. (2009), "New protein-resistant coatings for water filtration membranes based on quaternary ammonium and phosphonium polymers", J. Membrane Sci., 330, 104-116.
  21. He, X.C., Yu, H.Y., Tang, Z.Q., Liu, L.Q., Yan, M.G., Gu, J.S. and Wei, X.W. (2009), "Reducing protein fouling of a polypropylene microporous membrane by CO2 plasma surface modification", Desalination, 244, 80-89.
  22. Herrwerth, S., Eck, W., Reinhardt, S. and Grunze, M. (2003), "Factors that Determine the Protein Resistance of Oligoether Self-Assembled Monolayers − Internal Hydrophilicity, Terminal Hydrophilicity, and Lateral Packing Density", J. Am. Chem. Soc., 125(31), 9359-9366.
  23. Hester, J.F. and Mayes, A.M. (2002), "Design and performance of foul-resistant poly(vinylidene fluoride) membranes prepared in a single-step by surface segregation", J. Membrane Sci., 202(1-2), 119-135.
  24. Higuchi, A., Iwata, N., Tsubaki, M. and Nakagawa, T. (1988), "Surface-modified Polysulfone Hollow Fibers", J. Appl. Polym. Sci., 36, 1753-1767.
  25. Higuchi, A., Iwata, N. and Nakagawa, T. (1990), "Surface Modified Polysulfone Hollow Fibers. II. Fibers having $CH_{2}CH_{2}CH_{2}SO_{3}$ − Segments and Immersed in HCl Solution", J. Appl. Polym. Sci., 40, 709-717.
  26. Higuchi, A., Koga, H. and Nakagawa, T. (1992), "Surface modified polysulfone hollow fibers. IV. chloromethylated fibers and their derivatives", J. Appl. Polym. Sci., 46, 449-457.
  27. Higuchi, A., Shirano, K., Harashima, M., Yoon, B.O., Hara, M., Hattori, M. and Imamura, K. (2002), "Chemically modified polysulfone hollow fibers with vinylpyrrolidone having improved blood compatibility", Biomaterials, 23(13), 2659-2666.
  28. Higuchi, A., Hashiba, H., Hayashi, R., Yoon, B.O., Hattori, M. and Hara, H. (2004a), "Chemically modified polysulfone hollow fibers with zwitterionic sulfoalkylbetaine group having improved blood compatibility", ACS Symposium Series 876, 2004, chp 25.
  29. Higuchi, A., Hashiba, H., Hayashi, R., Yoon, B.O., Sakurai, M. and Hara, M. (2004b), "Serum protein and platelet adsorption on aspartic acid-immobilized polysulfone membranes", J. Biomat. Sci., Polym. E., 15(8), 1051-1063.
  30. Hilal, N., Kochkodan, V., Al-Khatib, L. and Levadna, T. (2004), "Surface modified polymeric membranes to reduce (bio)fouling: a microbiological study using E. coli", Desalination, 167(1-3), 293-300.
  31. Hu, M.X., Yang, Q. and Xu, Z.K. (2006), "Enhancing the hydrophilicity of polypropylene microporous membranes by the grafting of 2-hydroxyethyl methacrylate via a synergistic effect of photoinitiators", J. Membrane Sci., 285(1-2), 196-205.
  32. Hyun, J., Jang, H., Kim, K., Na, K. and Tak, T. (2006), "Restriction of biofouling in membrane filtration using a brush-like polymer containing oligoethylene glycol side chains", J. Membrane Sci., 282(1-2), 52-59.
  33. Ishihara, K., Fukumoto, K., Iwasaki, Y. and Nakabayashi, N. (1999a), "Modification of polysulfone with phospholipid polymer for improvement of the blood compatibility. Part 1. Surface characterization", Biomaterials, 20, 1545-1551.
  34. Ishihara, K., Fukumoto, K., Iwasaki, Y. and Nakabayashi, N. (1999b), "Modification of polysulfone with phospholipid polymer for improvement of the blood compatibility. Part 2. Protein adsorption and platelet adhension", Biomaterials, 20, 1553-1559.
  35. Ishihara, K., Iwasaki, Y., Ebihara, S., Shindo, Y. and Nakabayashi, N. (2000), "Photoinduced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on polyethylene membrane surface for obtaining blood cell adhesion resistance", Colloid Surface B, 18, 325-335.
  36. lto, Y., Kotera, S., Inabe, M., Kono, K. and Imanishi, Y. (1990), "Control of pore size of polycarbonate membrane with straight pores by poly(acrylic acid) grafts", Polymer, 31, 2157-2161.
  37. Kaeselev, B., Pieracci, J. and Belfort, G. (2001), "Photoinduced grafting of ultrafiltration membranes: comparison of poly(ether sulfone) and poly(sulfone)", J. Membrane Sci., 194(2), 245-261.
  38. Kawai, F. (2002), "Microbial degradation of polyethers", Appl. Microbiol. Biot., 58, 30-38.
  39. Kim, J.H., Kang, M.S. and Kim, C.K. (2005), "Fabrication of membranes for the liquid separation. 1. Ultrafiltration membranes prepared from novel miscible blends of polysulfone and poly(1-vinylpyrrolidone-coacrylonitrile) copolymers", J. Membrane Sci., 265(1-2), 167-175.
  40. Kull, K.R., Steen, M.L. and Fisher, E.R. (2005), "Surface modification with nitrogen-containing plasmas to produce hydrophilic, low-fouling membranes", J. Membrane Sci., 246(2), 203-215.
  41. Li, L., Yan, G.P. and Wu, J.Y. (2009), "Modification of polysulfone membranes via surface-initiated atom transfer radical polymerization and their antifouling properties", J. Appl. Polym. Sci., 111, 1942-1946.
  42. Liu, S.X., Kim, J.T., Kim, S. and Singh, M. (2009), "The Effect of Polymer Surface Modification Via Interfacial Polymerization on Polymer-Protein Interaction", J. Appl. Polym. Sci., 112(3), 1704-1715.
  43. Liu, Z.M., Xu, Z.K., Wan, L.S., Wu, J. and Ulbricht, M. (2005), "Surface modification of polypropylene microfiltration membranes by the immobilization of poly (N-vinyl-2-pyrrolidone): a facile plasma approach", J. Membrane Sci., 249(1-2), 21-31.
  44. Louie, J.S., Pinnau, I., Ciobanu, I., Ishida, K.P., Ng, A. and Reinhard, M. (2006), "Effects of polyether-polyamide block copolymer coating on performance and fouling of reverse osmosis membranes", J. Membrane Sci., 280, 762-770.
  45. Mehta, A. and Zydney, A.L. (2008), "Effect of spacer arm length on the performance of charge-modified ultrafiltration membranes", J. Membrane Sci., 313, 304-314.
  46. Nabe, A., Staude, E. and Belfort, G. (1997), "Surface modification of polysulfone ultrafiltration membranes and fouling by BSA solutions", J. Membrane Sci., 133, 57-72.
  47. Nie, F.Q., Xu, Z.K., Yang, Q., Wu, J. and Wan, L. (2004), "Surface modification of poly(acrylonitrile-co-maleic acid) membranes by the immobilization of poly(ethylene glycol)", J. Membrane Sci., 235(1-2), 147-155.
  48. Nunes, S.P., Sforca, M.L. and Peinemann, K.V. (1995), "Dense hydrophilic composite membranes for ultrafiltration", J. Membrane Sci., 106, 49-56.
  49. Qiu, C.Q., Nguyen, Q.T. and Ping, Z.H. (2007), "Surface modification of cardo polyetherketone ultrafiltration membrane by photo-grafted copolymers to obtain nanofiltration membranes", J. Membrane Sci., 295(1-2), 88- 94.
  50. Pieracci, J., Crivello, J.V. and Belfort, G. (1999), "Photochemical modification of 10 kDa polyethersulfone ultrafiltration membranes for reduction of biofouling", J. Membrane Sci., 156(2), 223-240.
  51. Rahimpour, A., Madaeni, S.S. and Mehdipour-Ataei, S. (2008), "Synthesis of a novel poly(amide-imide) (PAI) and preparation and characterization of PAI blended polyethersulfone (PES) membranes", J. Membrane Sci., 311(1-2), 349-359.
  52. Rajam, S. and Ho, C.C. (2006), "Graft coupling of PEO to mixed cellulose esters microfiltration membranes by UV irradiation", J. Membrane Sci., 281(1-2), 211-218.
  53. Shi, Q., Su, Y.L., Zhu, S.P., Li, C., Zhao, Y. and Jiang, Z. (2007), "A facile method for synthesis of pegylated polyethersulfone and its application in fabrication of antifouling ultrafiltration membrane", J. Membrane Sci., 303(1-2), 204-212.
  54. Su, Y.L., Li, C., Zhao, W., Shi, Q., Wang, H., Jiang, Z. and Zhu, S. (2008), "Modification of polyethersulfone ultrafiltration membranes with phosphorylcholine copolymer can remarkably improve the antifouling and permeation properties", J. Membrane Sci., 322, 171-177.
  55. Susanto, H., Balakrishnan, M. and Ulbricht, M. (2007), "Via surface functionalization by photograft copolymerization to low-fouling polyethersulfone-based ultrafiltration membranes", J. Membrane Sci., 288, 157-167.
  56. Takahashi, A. and Hisatomi, H. (2009), Hydrophilic monomers suppress the adsorption of plasma protein onto a poly(vinylidene fluoride) membrane, Molecular Medicine Reports, 2, 749-752.
  57. Taniguchi, M., Kilduff, J.E. and Belfort, G. (2003), "Low fouling synthetic membranes by UV-assisted graft polymerization: monomer selection to mitigate fouling by natural organic matter", J. Membrane Sci., 222(1-2), 59-70.
  58. Tian, M., Zhong, R., Sun, S.D., Zhao, C., Huang, Z. and Yue, Y. (2007), "Comparison of two approaches to grafting hydrophilic polymer chains onto polysulfone films", J. Membrane Sci., 103, 3818-3826.
  59. Toyomoto, K. and Higuchi, A. (1992), Microfiltration and Ultrafiltration, in Membrane Science and Technology (Eds. Y. Osada and T. Nakagawa), Marcel Dekker Inc., New York, p289-331.
  60. Ulbricht, M. and Belfort, G. (1996), "Surface modification of ultrafiltration membranes by low temperature plasma .2. Graft polymerization onto polyacrylonitrile and polysulfone", J. Membrane Sci., 111, 193-215.
  61. Ulbricht, M., Matuschewski, H., Oechel, A. and Hicke, H.G. (1996a), "Photo-induced graft polymerization surface modifications for the preparation of hydrophilic and low-protein-adsorbing ultrafiltration membranes", J. Membrane Sci., 115(1), 31-47.
  62. Ulbricht, M., Riedel, M. and Marx, U. (1996b), "Novel photochemical surface functionalization of polysulfone ultrafiltration membranes for covalent immobilization of biomolecules", J. Membrane Sci., 120, 239-259.
  63. Vanderah, D.J., La, H., Naff, J., Silin, V. and Rubinson, K.A. (2004), "Control of protein adsorption: molecular level structural and spatial variables", J. Am. Chem. Soc., 126, 13639-13641.
  64. Vanderah, D.J., Vierling, R.J. and Walker, M.L. (2009), "Oligo(ethylene oxide) Self-Assembled Monolayers, with Self-Limiting Packing Densities for the Inhibition of Nonspecific Protein Adsorption", Langmuir, 25, 5026-5030.
  65. Wang, Y., Kim, J.H., Choo, K.H., Lee, Y.S. and Lee, C.H. (2000), "Hydrophilic modification of polypropylene microfiltration membranes by ozone-induced graft polymerization", J. Membrane Sci.,169(2), 269-276.
  66. Wang, Y.Q., Su, Y.L., Ma, X.L., Sun, Q. and Jiang, Z.Y. (2006), "Pluronic polymers and polyethersulfone blend membranes with improved fouling-resistant ability and ultrafiltration performance", J. Membrane Sci., 283(1- 2), 440-447.
  67. Wavhal, D.S. and Fisher, E.R. (2002), "Hydrophilic modification of polyethersulfone membranes by low temperature plasma-induced graft polymerization", J. Membrane Sci., 209, 255-269.
  68. Yu, H.Y., Liu, L.Q., Tang, Z.Q., Yan, M.G., Gu, J.S. and Wei, X.W. (2008), "Mitigated membrane fouling in an SMBR by surface modification", J. Membrane Sci., 310(1-2), 409-417.
  69. Zhao, C.S., Liu, X.D., Rikimaru, S., Nomizu, M. and Nishi, N. (2003), "Surface characterization of polysulfone membranes modified by DNA immobilization", J. Membrane Sci., 214(2), 179-189
  70. Zhao, Y.H., Qian, Y.L., Pang, D.X., Zhu, B.K. and Xu, Y.Y. (2007), "Porous membranes modified by hyperbranched polymers II. Effect of the arm length of amphiphilic hyperbranched-star polymers on the hydrophilicity and protein resistance of poly(vinylidene fluoride) membranes", J. Membrane Sci., 304(1-2), 138-147.
  71. Zhao, Y.H., Qian, Y.L., Zhu, B.K. and Xu, Y.Y. (2008a), "Modification of porous poly(vinylidene fluoride) membrane using amphiphilic polymers with different structures in phase inversion process", J. Membrane Sci., 310(1-2), 567-576.
  72. Zhao, W., Su, Y.L., Li, C., Shi, Q., Ning, X. and Jiang, Z. (2008b), "Fabrication of antifouling polyethersulfone ultrafiltration membranes using Pluronic F127 as both surface modifier and pore-forming agent", J. Membrane Sci., 318(1-2), 405-412.
  73. Zhang, M.G., Nguyen, Q.T. and Ping, Z.H. (2009), "Hydrophilic modification of poly (vinylidene fluoride) microporous membrane", J. Membrane Sci., 327, 78-86.
  74. Zhou, J., Meng, S., Guo, Z., Du, Q. and Zhong, W. (2007), "Phosphorylcholine-modified poly (ethylene-co-vinyl alcohol) microporous membranes with improved protein-adsorption-resistance property", J. Membrane Sci., 305(1-2), 279-286.

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