Preparation And Applications Of Novel Magnetic Microspheres

Rapid evolution of life sciences in the last decades calls for the development of fast and robust analysis and separation of bio-macroparticles. Recently, separation of organisms/biomacroparticles using magnetically responsive particles has emerged as a promising technique, which promises easy manipulation, automation, and miniaturization of the separation and purification process. In China, however , this technique has not found widespread applications primarily because of the lack of key techniques for preparation of high-performance magnetic microspheres and the insufficiant R & D activities devoted to the exploration of novel magnetic separations. The objective of this thesis is three-fold: (1) to establish propietory processes for preparation of novel magnetic microspheres, (2) to study the migration behaviour of the magnetic particles under the influence of moving magnetic field, and (3) to explore the application of magnetically responsive liposomes in evaluation of cross-membrane transport for drugs.Magnetic particles with spherical shape, uniform size distribution, good stability in suspension, high magnetic responsiveness and superparamagnetism are indispensable to biomagnetic separations. In order to meet these needs, we developed two methods for preparation of uniform magnetic microspheres. In the first method, magnetic fluid comprised of magnetic nanoparticles dispersed in aqueous solution was prepared by co-precipitation. The magnetic nanoparticles stabilized by electrostatic interactions were then incorporated into urea-formaldehyde polymer microspheres by precipitation polymerization. This method offers advantages of easy manipulation and shorter reacting time. In the second method, eletrostatic self-assembly approach was used to prepare Core-Shell magnetic microspheres with homogeneous size distribution and good dispersion.The magnetic field-induced migration of particles in liquid is a highly-promising technique for the separation of bioacitve particles. In this thesis, the migration of magnetic particles by means of rotating magnetic field was investigated. In traditional magnetic cell separation methods, such as batch and continuous magnetic cell sorting, the applied external magnetic fields are all static. Because the influence of the static magnetic field decays exponentially with the distance, weakly labeled cells cannot move sufficiently to be separated, thus decreasing the recovery. In order to increase enrichment rate, we developed a simulated system of magnetic cell separation under rotating magnetic field. We investigated migration behavior of single magnetic microsphere and separation of particles with different sizes or susceptibilities, thus establishing preliminary model of cell separation.Magnetoliposomes (MLs), magnetic particles coated with a lipid layer, can be used as membrane evaluation system. For this purpose, membrane phospholipid molecules were covalently bonded to magnetic silica particles at high molecular surface densities. Results show that drug transport behavior of the MLs is similar to that of immobilized artificial membrane HPLC. thus it can be used to evaluate drug membrane partition coefficients. In this thesis, lecithin was coated on the surface of magnetic microspheres to mimic cell membrane, in the process ,advantages of magnetic bio-separation are exhibited,and we determined partition coefficients of four groups of drugs and compared with n-octanol/water partition cefficients.