Thermally-modulated on/off-adsorption materials for pharmaceutical protein purification

Kenichi Nagase, Jun Kobayashi, Akihiko Kikuchi, Yoshikatsu Akiyama, Hideko Kanazawa, Teruo Okano

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)


For the development of temperature-responsive adsorption materials for pharmaceutical protein purification, poly(N-isopropylacrylamide-co-N,N-dimethylaminopropylacrylamide-co-N-tert-butylacrylamide) (P(IPAAm-co-DMAPAAm-co-tBAAm) brush grafted silica beads were prepared through a surface-initiated atom transfer radical polymerization (ATRP). The prepared silica beads as a chromatographic stationary phase were evaluated by observing their thermo-responsive elution profiles of plasma proteins including human serum albumin (HSA) and γ-globulin. Chromatograms of two proteins indicated that negatively-charged HSA was adsorbed on the cationic copolymer brush modified silica beads at higher temperatures with low concentration of phosphate buffer (PB) (pH 7.0) as a mobile phase. The HSA adsorption was attributed to (1) an enhanced electrostatic interaction with the cationic copolymer brush at low concentration of PB and (2) an increased hydrophobic interaction from the dehydrated copolymer at high temperature. Step-temperature gradient enabled HSA and γ-globulin to be separated by the modulation of HSA adsorption/desorption onto the copolymer brush grafted silica beads. These results suggested that the prepared copolymer brush grafted silica beads adsorbed negatively-charged proteins both through electrostatic and hydrophobic interactions by the modulation of column temperature and gave attractive adsorption materials for protein purification process.

Original languageEnglish
Pages (from-to)619-627
Number of pages9
Issue number2
Publication statusPublished - 2011 Jan
Externally publishedYes


  • Adsorption
  • Albumin
  • Plasma proteins
  • Protein adsorption
  • Silica
  • Surface modification

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials


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