Magnetorelaxometry

In magnetorelaxometry, the magnetic moments of the nanoparticles are aligned by a magnetizing field pulse of amplitude of a few mT and length of some seconds, and after abruptly switching off the field, the decay of the net magnetic moment of the sample is measured. The magnetic flux density from the sample’s net magnetic moment is measured using high-sensitivity magnetic field sensors, such as SQUIDs and fluxgates. As measurements of the AC susceptibility, magnetorelaxometry provides information on the relaxation times (magnetization dynamics) for MNPs in a carrier liquid or for immobilized MNPs. The lower limit of the accessible time constants is generally limited by the switch-off time of the magnetizing field pulse which typically amounts to 0.1 ms. For fluxgate sensors, another limit is given by the sensor bandwidth, utilizing SQUIDs, the signal is generally recorded after some dead-time (0.5 ms-1 ms) caused by slew-rate limitations of the readout electronics. The upper limit is given by the measurement time which mostly amounts to a few seconds, but which can be arbitrarily increased. The lower limit of a few 0.1 ms defines the smallest size for MNP cores which contribute to the signal in the measurement window and which amounts for magnetite (Fe3O4) to about 18 nm depending on the value of the effective anisotropy constant.

The analysis of MRX curves is mostly based on the moment superposition model neglecting magnetic dipolar interactions between individual particles. In contrast to AC susceptometry, magnetorelaxometry is a comparably fast measurement, an unaveraged measurement lasts typically a few seconds. To determine parameters of the magnetic cores, measurements are performed on immobilized samples, i.e., relaxation takes place only via the Néel mechanism. To obtain more reliable data sets from the MRX curve fits, it is recommendable to utilize parametric dependencies. Temperature dependent magnetorelaxometry can be used to investigate the temperature dependence of the anisotropy energies of the MNPs since measurements at lower temperatures allow one to see signal contributions of smaller size cores. From the signal the effective relaxation time can be determined and thus, if the hydrodynamic parameters of the carrier liquid are known, the nanoparticle’s core and hydrodynamic size distribution. On the other hand, if the core and hydrodynamic size distribution of MNP are known from reference measurements, MNP will act in magnetorelaxometry as local probes providing information on their binding state or on their local rotational mobility when dispersed in different media, biological cells or tissue.

By investigating concentration series of MNP in biological media, valuable information on their colloidal stability can be gained. Magnetorelaxometrometry can thus act as the readout method in different variants of an immunoassay based on the binding of surface functionalized MNP (MARIA, magnetic relaxation immunoassay). Magnetorelaxometry is an integral method, which means that the readout signal is generated by all MNP in the excited volume. This property together with the signal shape that is specific for MNP enables the quantification of absolute MNP content in extended organs or even whole animals by magnetorelaxometry. The noninvasive character of the method allows for long-term monitoring of animals, for example of magnetically labeled stem cells. Recent developments of magnetorelaxometry focus on spatially resolved quantitative MNP measurements in larger volumes. The quantitative and structural informations gained by MRX are crucial for the assessment of toxicity and bioimpact of MNP that are used as therapeutic or diagnostic agents or that are accidentally polluting the environment as a byproduct of other industrial processes (i.e. iron corrosion, laser printer dye, leakage of magnetic bearings).

Magnetorelaxometry using functionalized MNPs allows designing of homogenous assay layouts without washing steps, since the simultaneous response of bound and unbound MNP can be separated by their specific signal shapes. This has been useful in the observation of binding kinetics during an ongoing biochemical reaction. Furthermore, due to the wide amplitude range of magnetorelaxometry, a parallel observation of the reaction using a dilution series of the analyte was possible. This enabled the observation of the prozone or “hook effect” in the MRX relevant parameters like relaxation time or hydrodynamic diameter. Using the a priori known MNP concentration, the maximum of the prozone effect determined the unknown analyte concentration, noise susceptible relaxation amplitudes were not needed any longer in the analysis.

Project Partners

Project partners


	This project has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 604448