Biosensing Using Magnetic Particle Detection Techniques.

Magnetic particles are widely used as signal labels in a variety of biological sensing applications, such as molecular detection and related strategies that rely on ligand-receptor binding. In this review, we explore the fundamental concepts involved in designing magnetic particles for biosensing applications and the techniques used to detect them. First, we briefly describe the magnetic properties that are important for bio-sensing applications and highlight the associated key parameters (such as the starting materials, size, functionalization methods, and bio-conjugation strategies). Subsequently, we focus on magnetic sensing applications that utilize several types of magnetic detection techniques: spintronic sensors, nuclear magnetic resonance (NMR) sensors, superconducting quantum interference devices (SQUIDs), sensors based on the atomic magnetometer (AM), and others. From the studies reported, we note that the size of the MPs is one of the most important factors in choosing a sensing technique.

Ultrasensitive Magnetic Nanoparticle Detector for Biosensor Applications.

Ta/Ru/Co/Ru/Co/Cu/Co/Ni80Fe20/Ta spin-valve giant magnetoresistive (GMR) multilayers were deposited using UHV magnetron sputtering and optimized to achieve a 13% GMR ratio before patterning. The GMR multilayer was patterned into 12 sensor arrays using a combination of e-beam and optical lithographies. Arrays were constructed with 400 nm × 400 nm and 400 nm × 200 nm sensors for the detection of reporter nanoparticles. Nanoparticle detection was based on measuring the shift in high-to-low resistance switching field of the GMR sensors in the presence of magnetic particle(s). Due to shape anisotropy and the corresponding demag field, the resistance state switching fields were significantly larger and the switching field distribution significantly broader in the 400 nm × 200 nm sensors as compared to the 400 nm × 400 nm sensors. Thus, sensor arrays with 400 nm × 400 nm dimensions were used for the demonstration of particle detection. Detection of a single 225 nm Fe3O4 magnetic nanoparticle and a small number (~10) of 100 nm nanoparticles was demonstrated. With appropriate functionalization for biomolecular recognition, submicron GMR sensor arrays can serve as the basis of ultrasensitive chemical and biological sensors.

Enzymatic conversion of magnetic nanoparticles to a non-magnetic precipitate: a new approach to magnetic sensing.

Magnetic sensing utilizes the detection of biomolecule-conjugated magnetic nanoparticles (MNPs). Our new strategy offers a novel approach to magnetic sensing where in situ conversion produces a "loss of signal" in the sensing device. This report demonstrates the enzymatic conversion of Fe3O4 MNPs to a non-magnetic precipitate via reduction by l-ascorbic acid generated by the action of alkaline phosphatase.

Enzymatic synthesis of magnetic nanoparticles.

We report the first in vitro enzymatic synthesis of paramagnetic and antiferromagnetic nanoparticles toward magnetic ELISA reporting. With our procedure, alkaline phosphatase catalyzes the dephosphorylation of l-ascorbic-2-phosphate, which then serves as a reducing agent for salts of iron, gadolinium, and holmium, forming magnetic precipitates of Fe45±14Gd5±2O50±15 and Fe42±4Ho6±4O52±5. The nanoparticles were found to be paramagnetic at 300 K and antiferromagnetic under 25 K. Although weakly magnetic at 300 K, the room-temperature magnetization of the nanoparticles found here is considerably greater than that of analogous chemically-synthesized LnxFeyOz (Ln = Gd, Ho) samples reported previously. At 5 K, the nanoparticles showed a significantly higher saturation magnetization of 45 and 30 emu/g for Fe45±14Gd5±2O50±15 and Fe42±4Ho6±4O52±5, respectively. Our approach of enzymatically synthesizing magnetic labels reduces the cost and avoids diffusional mass-transfer limitations associated with pre-synthesized magnetic reporter particles, while retaining the advantages of magnetic sensing.

Tuning the magnetic properties of nanoparticles.

The tremendous interest in magnetic nanoparticles (MNPs) is reflected in published research that ranges from novel methods of synthesis of unique nanoparticle shapes and composite structures to a large number of MNP characterization techniques, and finally to their use in many biomedical and nanotechnology-based applications. The knowledge gained from this vast body of research can be made more useful if we organize the associated results to correlate key magnetic properties with the parameters that influence them. Tuning these properties of MNPs will allow us to tailor nanoparticles for specific applications, thus increasing their effectiveness. The complex magnetic behavior exhibited by MNPs is governed by many factors; these factors can either improve or adversely affect the desired magnetic properties. In this report, we have outlined a matrix of parameters that can be varied to tune the magnetic properties of nanoparticles. For practical utility, this review focuses on the effect of size, shape, composition, and shell-core structure on saturation magnetization, coercivity, blocking temperature, and relaxation time.

Vibrational response of clusters of Fe3O4 nanoparticles patterned on glass surfaces investigated with magnetic sample modulation AFM.

The vibration of Fe3O4 nanoparticles in response to an alternating magnetic field can be sensitively detected using contact mode atomic force microscopy (AFM) combined with selective modulation of magnetic domains. While imaging patterned samples of magnetic nanoparticles with contact mode AFM, a magnetic field was applied to drive sample vibration. The field altered in polarity and strength according to parameters of an AC current applied to a solenoid located under the sample. The vibration of Fe3O4 nanoparticles was detected by a nonmagnetic AFM tip to map the changes in frequency and amplitude of the vibrating sample at the level of individual Fe3O4 nanoparticles and clusters. Colloidal lithography, was used to prepare patterns of Fe3O4 nanoparticles on a glass surface using the basic steps of mixing, drying and removing the surface template of latex spheres. Monodisperse latex spheres were used to guide the deposition of magnetic nanoparticles in the spaces between the close-packed spheres of the latex film. With a mixture approach of "two-particle" lithography, 2D arrays of patterned aggregates of metal nanoparticles were generated which formed a periodic, well-defined arrangement that was suitable for subsequent characterizations with magnetic sample modulation (MSM).

Near-infrared-responsive, superparamagnetic Au@Co nanochains.

This manuscript describes a new type of nanomaterial, namely superparamagnetic Au@Co nanochains with optical extinctions in the near infrared (NIR). The Au@Co nanochains were synthesized via a one-pot galvanic replacement route involving a redox-transmetalation process in aqueous medium, where Au salt was reduced to form Au shells on Co seed templates, affording hollow Au@Co nanochains. The Au shells serve not only as a protective coating for the Co nanochain cores, but also to give rise to the optical properties of these unique nanostructures. Importantly, these bifunctional, magneto-optical Au@Co nanochains combine the advantages of nanophotonics (extinction at ca. 900 nm) and nanomagnetism (superparamagnetism) and provide a potentially useful new nanoarchitecture for biomedical or catalytic applications that can benefit from both activation by light and manipulation using an external magnetic field.

Magnetic Sensing Potential of Fe3O4 Nanocubes Exceeds That of Fe3O4 Nanospheres.

This paper highlights the relation between the shape of iron oxide (Fe3O4) particles and their magnetic sensing ability. We synthesized Fe3O4 nanocubes and nanospheres having tunable sizes via solvothermal and thermal decomposition synthesis reactions, respectively, to obtain samples in which the volumes and body diagonals/diameters were equivalent. Vibrating sample magnetometry (VSM) data showed that the saturation magnetization (Ms) and coercivity of 100-225 nm cubic magnetic nanoparticles (MNPs) were, respectively, 1.4-3.0 and 1.1-8.4 times those of spherical MNPs on a same-volume and same-body diagonal/diameter basis. The Curie temperature for the cubic Fe3O4 MNPs for each size was also higher than that of the corresponding spherical MNPs; furthermore, the cubic Fe3O4 MNPs were more crystalline than the corresponding spherical MNPs. For applications relying on both higher contact area and enhanced magnetic properties, higher-Ms Fe3O4 nanocubes offer distinct advantages over Fe3O4 nanospheres of the same-volume or same-body diagonal/diameter. We evaluated the sensing potential of our synthesized MNPs using giant magnetoresistive (GMR) sensing and force-induced remnant magnetization spectroscopy (FIRMS). Preliminary data obtained by GMR sensing confirmed that the nanocubes exhibited a distinct sensitivity advantage over the nanospheres. Similarly, FIRMS data showed that when subjected to the same force at the same initial concentration, a greater number of nanocubes remained bound to the sensor surface because of higher surface contact area. Because greater binding and higher Ms translate to stronger signal and better analytical sensitivity, nanocubes are an attractive alternative to nanospheres in sensing applications.

Multi-responsive hybrid particles: thermo-, pH-, photo-, and magneto-responsive magnetic hydrogel cores with gold nanorod optical triggers.

The research strategy described in this manuscript harnesses the attractive properties of hydrogels, gold nanorods (Aurods), and magnetic nanoparticles (MNPs) by synthesizing one unique multi-responsive nanostructure. This novel hybrid structure consists of silica-coated magnetic particles encapsulated within a thermo-responsive P(NIPAM-co-AA) hydrogel network on which Aurods are assembled. Furthermore, this research demonstrates that these composite particles respond to several forms of external stimuli (temperature, pH, light, and/or applied magnetic field) owing to their specific architecture. Exposure of the hybrid particles to external stimuli led to a systematic and reversible variation in the hydrodynamic diameter (swelling-deswelling) and thus in the optical properties of the hybrid particles (red-shifting of the plasmon band). Such stimuli-responsive volume changes can be effectively exploited in drug-delivery applications.

Conditioning of Cardiovascular Tissue Using a Noncontact Magnetic Stretch Bioreactor with Embedded Magnetic Nanoparticles.

Bioreactor systems, an integral component of tissue engineering, are designed to simulate complex in vivo conditions to impart functionality to artificial tissue. All standard forms of stretch bioreactors require physical contact with artificial heart muscle (AHM). However, we believe that noncontact stretch bioreactors have the potential to lead to higher functional benefit of AHM. Our work is focused on the fabrication of a noncontact magnetic stretch bioreactor (MSB) that uses magnetic nanoparticles to simulate stretch conditions to impart functionality. During our development of this system, we applied magnetically induced stretch conditioning through application of an oscillating magnetic field to a ferromagnetic heart muscle model. Fibrin scaffolds were loaded with magnetic nanoparticles prior to tissue model formation. Oscillating magnetic fields were applied by a novel bioreactor system through displacement of a neodymium magnet. The addition of commercially obtained iron(III) oxide (Fe2O3) in sufficient quantities to allow for physiologically relevant stretches (15% axial displacement) caused toxic effects after 4 days of culture. In contrast, loading scaffolds with monodispersed, high-saturation-magnetization magnetite (Fe3O4) nanoparticles specifically prepared for these experiments increased the field strength of the magnetized fibrin 10-fold over polydispersed, low-saturation magnetization, Fe2O3. Additionally, loading with Fe3O4 enabled magnetically actuated stretching with markedly reduced toxicity over 8 days of culture. Using a 20% stretch 0.5 Hz protocol, we observed a significant increase in twitch force over controls at days 4 and 6. This work provides a technology for controlled noncontact mechanical stretch to condition AHM.

Cubic Silica-Coated and Amine-Functionalized FeCo Nanoparticles with High Saturation Magnetization.

By systematically varying the reaction parameters in a liquid-phase reduction reaction, large FeCo nanocubes with tunable body diagonal lengths of 175, 350, and 450 nm were synthesized. The nanocubes were initially stabilized with poly(vinyl pyrrolidone) (PVP) and then coated with a relatively thin layer of silica (~55 nm thick), which allowed them to retain their cubic shape. The magnetization curves showed that the PVP-stabilized nanocubes exhibited a high saturation magnetization of 167 ± 4 emu/g. The saturation magnetization, however, decreased upon coating with silica to 146 ± 13 emu/g for the particles with 350 and 450 nm FeCo cores and 48 ± 1 emu/g for the particles with 175 nm FeCo cores. The silica-coated FeCo nanocubes were then functionalized with 3-(aminopropyl)-trimethoxysilane (APTMS), and a layer of surface-bound nanoparticle was generated by exposing the resultant amine-functionalized nanocubes to self-assembled monolayers (SAMs) on gold terminated with carboxylic-acid groups.