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27 DEVELOPMENT OF THE THERMORESPONSIVE MAGNETIC NANOPARTICLE                  APPLICATIONS


                                          Cl     -  +     NH 2  aq. NaCO 3  / ether  O
                                              +  Cl H 3 N                           NH 2
                                                                               N
                                        O               O
                                                                               H   O
                                                 O                                        O
                                   H           HN  NH H      DPPA / TEA / DMF           HN  NH H
                                           +
                                             -
                                   N    NH 3 Cl +  H      OH                 H    H     H
                                                   S                         N    N        S
                                  O                        O
                                                                            O      O
                  Figure 27.3
                  Synthesis schemes of N-acryloyl glycine amide and a biotin derivative.
                      Biotin
                                             Avidin




                                                 Biotinylated compound

                           Thermoresponsive
                          magnetic nanoparticle


                            Biotinylated compound

                                                                                            S Substrate
                                                          A T G C A T
                            Biotin                                                          P Product
                                                           Nucleic acid
                                    Antibody                                        Enzyme



                  Figure 27.4
                  Immobilization of a biomolecule to a thermoresponsive magnetic nanoparticle using the biotin–avidin interaction.



                  contain biotins, these thermoresponsive magnetic  The following sections introduce specific applica-
                  nanoparticles can specifically form bonds with  tions of Therma-Max to the biotechnology field.
                  avidins and a variety of biological molecules, such as
                  biotinylated proteins and DNAs, through the biotins
                  on the particle surface (Fig. 27.4).           4. Application examples of the thermoresponsive
                    The thermoresponsive magnetic nanoparticles do  magnetic nanoparticles to the biotechnology field
                  not settle spontaneously at room temperature and can-
                  not be separated magnetically, even by using a fairly  (1) Application to the diagnosis field
                  strong magnet. However, when placed in an ice bath,  Due to its easy separation from the sample after con-
                  they instantly coagulate and can be easily separated  necting antigens, the magnetic nanoparticle coupled
                  magnetically (Fig. 27.5). Moreover, the coagulated  with antibodies is a diagnosis agent of some potential.
                  particles can be made to revert to a completely dis-  Fig. 27.6 shows a typical example of an antigen detec-
                  persed state by raising the temperature.  As just  tion method via a sandwich method using the anti-
                  described, the thermoresponsive magnetic nanomole-  body-coupled magnetic nanoparticles.
                  cules can be stored as a completely uniform solution,  In case specific antigens exist in the sample, these
                  but can rapidly coagulate to become magnetically  will be adsorbed by the antibody-coupled magnetic
                  separable by applying heat, rendering them a suitable  nanoparticles. Following the adsorption, the labeled
                  material for a variety of automatic rapid analyses.  antibodies (secondary antibodies) are added and the

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