Giant Magnetoresistive Biosensors for Time-Domain Magnetorelaxometry: A Theoretical Investigation and Progress Toward an Immunoassay.

Magnetorelaxometry (MRX) is a promising new biosensing technique for point-of-care diagnostics. Historically, magnetic sensors have been primarily used to monitor the stray field of magnetic nanoparticles bound to analytes of interest for immunoassays and flow cytometers. In MRX, the magnetic nanoparticles (MNPs) are first magnetized and then the temporal response is monitored after removing the magnetic field. This new sensing modality is insensitive to the magnetic field homogeneity making it more amenable to low-power portable applications. In this work, we systematically investigated time-domain MRX by measuring the signal dependence on the applied field, magnetization time, and magnetic core size. The extracted characteristic times varied for different magnetic MNPs, exhibiting unique magnetic signatures. We also measured the signal contribution based on the MNP location and correlated the coverage with measured signal amplitude. Lastly, we demonstrated, for the first time, a GMR-based time-domain MRX bioassay. This approach validates the feasibility of immunoassays using GMR-based MRX and provides an alternative platform for point-of-care diagnostics

Magnetic Nanoparticle Sensors

Many types of biosensors employ magnetic nanoparticles (diameter = 5–300 nm) or magnetic particles (diameter = 300–5,000 nm) which have been surface functionalized to recognize specific molecular targets. Here we cover three types of biosensors that employ different biosensing principles, magnetic materials, and instrumentation. The first type consists of magnetic relaxation switch assay-sensors, which are based on the effects magnetic particles exert on water proton relaxation rates. The second type consists of magnetic particle relaxation sensors, which determine the relaxation of the magnetic moment within the magnetic particle. The third type is magnetoresistive sensors, which detect the presence of magnetic particles on the surface of electronic devices that are sensitive to changes in magnetic fields on their surface. Recent improvements in the design of magnetic nanoparticles (and magnetic particles), together with improvements in instrumentation, suggest that magnetic material-based biosensors may become widely used in the future

Homogeneous Biosensing Based on Magnetic Particle Labels

The growing availability of biomarker panels for molecular diagnostics is leading to an increasing need for fast and sensitive biosensing technologies that are applicable to point-of-care testing. In that regard, homogeneous measurement principles are especially relevant as they usually do not require extensive sample preparation procedures, thus reducing the total analysis time and maximizing ease-of-use. In this review, we focus on homogeneous biosensors for the in vitro detection of biomarkers. Within this broad range of biosensors, we concentrate on methods that apply magnetic particle labels. The advantage of such methods lies in the added possibility to manipulate the particle labels by applied magnetic fields, which can be exploited, for example, to decrease incubation times or to enhance the signal-to-noise-ratio of the measurement signal by applying frequency-selective detection. In our review, we discriminate the corresponding methods based on the nature of the acquired measurement signal, which can either be based on magnetic or optical detection. The underlying measurement principles of the different techniques are discussed, and biosensing examples for all techniques are reported, thereby demonstrating the broad applicability of homogeneous in vitro biosensing based on magnetic particle label actuation

Frequency-Domain Faraday Rotation Spectroscopy (FD-FRS) for Functionalized Particle and Biomolecule Characterization

In this study, the magnetically-induced vibrations of functionalized magnetic particle suspensions were probed for the development of a novel optical spectroscopy technique. Through this work (1) the frequency-dependence of the faraday rotation in ferrofluids and (2) the extension of this system to elucidating particle size and conformation as an alternative immunossay to costly and labor/time intensive Western Blotting and ELISA has been shown. With its sensitivity and specificity, this method has proven to be a promising multi-functional tool in biosensing, diagnostic, and therapeutic nanomedicine efforts. Due to its ubiquitous nature in all optically-transparent materials, the farady rotation, or circular birefringence, was developed as a robust and sensitive nanoscale biomolecule characterization technique through Brownian relaxation studies of particle suspensions. Current efforts have shown the applicability of this phenomenon in solid, pure liquid, and colloidal samples as well as simultaneous advancements of magnetic nanoparticle research in the magnetometric and magneto-optical regimes. By merging these two fields, a clinically relevant spectroscopy (fd-FRS, Frequency Domain Faraday Rotation Spectroscopy) was developed based on a newly revised model stemming from Debye relazation theory. Through this work, an optical bench with a variable permeability core electromagnet and a frequency-domain lock-in amplifier setup (DC to 20 kHz) have been used to distinguish between Fe3O4-core nanoparticles with functionalization layers of PEG4/PEG8 polymer with future applications involving the Anti-BSA/BSA antibody/antigen couple. Particle concentrations down to 500 nM (magnetic nanoparticles) and 0.01 Volume % (magnetic beads) were studied with diameters ranging from 200 nm to 1μm. currently, the characteristic peak corresponding to the out-of-phase relazation of the suspended particles has been elusive, despite a wide particle size distribution and the use of a balanced photodetector. Future work will involved highly monodisperse samples, faster scan times, and thermal characterization applications of fs-FRS