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NMR R1 and R2 relaxivities »
Magnetic nanoparticle bio-detection »
Magnetic hyperthermia measurements »
Magnetic nanoparticle bio-detection
Magnetic nanoparticles can be used in magnetic biosensing and some of the used NanoMag analysis methods can be used as detection principles. Chip-based platforms can be used to measure the dynamic magnetic response of the MNPs. It requires no external field (all magnetic fields are generated on-chip) and does not require magnetic shielding. Surface-based and volume-based assays can be used as bio-detection methods. Instead of using chip-based detection the dynamic properties can be measured by inductive coils, SQUIDs or fluxgate sensors of a whole sample volume and measuring the change in Brownian relaxation when the nanoparticles bind specifically to different analytes. Volume-based bioassays based on measurements of the dynamic rotation response of magnetic nanobeads in suspension can be used to detect biomarkers in a sample.
The ability of the nanobeads to rotate and adjust their direction along a changing magnetic field depends inversely on their hydrodynamic volume and is characterized by the Brownian relaxation frequency fB. The presence of biomolecules modifies the hydrodynamic volume of the particles either by a direct change of the particle size via their binding or by inducing agglutination of several particles (or several particle types). The particle properties (single-core/multi-core, thermally blocked/superparamagnetic, size distribution) have a strong impact on the Brownian relaxation behavior of the individual particles and on the dynamics of a particle ensemble in the presence and absence of magnetic fields. For example, strong magnetic interactions may lead to an undesirable particle clustering and sedimentation, whereas weaker magnetic interactions may make it possible to induce particle clustering by applying a magnetic field but also that these clusters spontaneously break up when the field is removed. Moreover, the particles should be nominally monodisperse as a wide size distribution will significantly broaden the dynamic magnetic response and hence may render biodetection by Brownian relaxation measurements unfeasible.
In the frequency domain, the complex magnetic susceptibility is measured vs. frequency. The in-phase magnetic susceptibility describes the ability of the particle moments to follow the alternating magnetic field and the out-of-phase magnetic susceptibility describes the component of the particle moments which is lagging behind the alternating magnetic field. The out-of-phase susceptibility assumes its maximum value at the median Brownian relaxation frequency fB. Brownian relaxation measurements can also be carried out in the time-domain by measuring the time-dependence of the magnetic response of a sample after a step in the applied magnetic field (typically switching the applied field off).
In a laboratory setting, Brownian relaxation measurements are carried out using commercial SQUID magnetometers (e.g. PPMS instrument from Quantum Design), custom built SQUID magnetometers (partner PTB), inductive coils (DynoMag instrument, partner ACREO) and fluxgate sensors (partner TUBS) that measure the dynamic magnetic response on a whole sample volume. An alternative approach, pursued by the DTU partner, is to integrate a magnetic read-out with a microfluidic channel. One of the read-out principles being pursued is to use magnetoresistive sensors that are placed within the microfluidic channel and excite these using an alternating current at frequency f. Magnetic beads in the vicinity of the sensor are magnetized by the magnetic field arising from the excitation current and give rise to a magnetic field acting back on the sensor. The complex dynamic magnetic response of the beads can then be measured in the second harmonic sensor signal by lock-in technique. The sensors operate at ambient temperature and without magnetic shielding. The measurements show the feasibility of the technique for measurements at frequencies up to MHz which will increase the biodetection sensitivity.