Intelligent thermoresponsive polymeric stationary phases for
aqueous chromatography of biological compounds
Akihiko Kikuchi, Teruo Okano
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1Kawadacho, Shinjuku,
Tokyo 162-8666, Japan
Received 5 November 2001; revised 21 January 2002; accepted 25 January 2002
Sensitive polymers with external physical, chemical, and electrical stimuli are termed as `intelligent materials'
and currently have been used in variety ®elds of engineering, and medicine. Numerous research papers utilizing
stimuli-responsive intelligent materials are found in the literature to date. In this manuscript, the authors described
several applications of surfaces and interfaces modi®ed with stimuli-responsive polymers for stimuli-responsive
surface property alteration and their application for the separation sciences. The special attention is paid to the
temperature responsive polymers, poly(N-isopropylacrylamide) (PIPAAm) and its derivatives as surface modi®ers
for novel `green' chromatography in which only aqueous mobile phase was utilized for separation of bioactive
compounds. Several factors were investigated and discussed the effects on separation of bioactive compounds;
these include the effects of the temperature-responsive hydrophilic/hydrophobic changes, copolymer composition,
graft polymer molecular architecture and the incorporation of charged groups. Furthermore, application of
PIPAAm-grafted surfaces for af®nity separation of proteins will be discussed. The technique has superior char-
acteristics in reducing organic wastes and costs to run chromatographic separation, and thus must be an envi-
ronmentally friendly separation tool. q 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Stimuli responsive polymer; Surface function; Biocompatibility; Hydrophilic/hydrophobic property alteration;
Charge density alteration; Chromatography; Penetration control; Aqueous mobile phase; Bioactive compounds; Separation;
Dye af®nity chromatography; Protein
1. Introduction ..................................................................1166
2. Molecular separation and permeation control through the stimuli-responsive pore size regulation . . . .1167
3. Thermoresponsive chromatography using poly(N-isopropylacrylamide) as column matrix ..........1169
4. Temperature-responsive wettability changes of PIPAAm-modi®ed surfaces ....................1172
Prog. Polym. Sci. 27 (2002) 1165±1193
0079-6700/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S 0079-6700(02)00013-8
* Corresponding author. Tel.: 181-3-3353-8111x30233; fax: 181-3-3359-6046.
E-mail address: email@example.com (T. Okano).