Brownian Relaxation Measurements of Magnetic Nanoparticles: Towards the Development of a Novel Biosensor System

Abstract: Magnetic measurements of the Brownian relaxation time of thermally blocked magnetic nanoparticles dispersed in a solution have been performed in order to determine the hydrodynamic size distribution of the particles. By measuring changes in the hydrodynamic size of the particles, the ammount of analytes attached to the surface of particles can be determined. Thereby a biosensor can be developed for detection of analytes in solution. The in-house developed instrumental measurement technique that has been used is based on an induction coil system. The coil system consists of two detection coils that form a first order gradiometer coupling and are placed symmetrically in the centre of an excitation coil.We have been able to show that it is possible to develop a biosensor system that enables quantitative determination of analytes in solution. Prostate specific antigen (PSA) has been used as analyte in a model assay system. PSA in solution has been detected using magnetic nanoparticles coated with a specific monoclonal PSA antibody. When PSA molecules became attached to the particle surface they caused a small change in the hydrodynamic radius of the particle and thereby induced a small change in the particle’s Brownian relaxation time which has been determined by magnetic measurements. The assay procedure described above enables homogeneous detection (in solution and not on a bulk surface) of analytes without any need for label molecules or washing steps. Thereby a cost effective immunoassay with few steps can be developed. Two different approaches using either frequency or time domain measurements have been applied when measuring the Brownian relaxation times for determination of the amount of analyte in solution. In the first method the frequency dependent complex susceptibility of the particles was measured. Such a measurement is very sensitive to small changes in Brownian relaxation times of the magnetic particles induced by analyte adsorption onto the particle surface. A theoretical model has been developed for quantitative determination of analyte concentrations. The second method is based on the measurement of the time dependent induced differential voltage of the particle system when subjected to pulsed magnetic fields. This method enables real-time monitoring of fast processes, such as for instance, cluster formation. Analytes were used as links between magnetic particles coated with two different complementary antibodies in order to induce particle clustering. The development of a biosensor involves many steps, such as: assay procedure development, instrumental measurement method development, optimization of magnetic characteristics of the magnetic particles and others. Examples will be given regarding PSA detection, using both frequency domain and time domain measurements. Detailed descriptions of the two measurement methods will be given, as well as a comparison of them. The sensitivity of the developed biosensor system for detection of PSA is at the moment ten times lower than the sensitivity of conventional immuno-assay systems. The sensitivity can and will be further increased by optimization of the biosensor system.