Lorena Maldonado-Camargo

Magnetic Assembly and Cross-Linking of Nanoparticles for Releasable Magnetic Microstructures.

This article describes a versatile method to fabricate magnetic microstructures with complex two-dimensional geometric shapes using magnetically assembled iron oxide (Fe3O4) and cobalt ferrite (CoFe2O4) nanoparticles. Magnetic pole patterns are imprinted into magnetizable media, onto which magnetic nanoparticles are assembled from a colloidal suspension into defined shapes via the shaped magnetic field gradients. The kinetics of this assembly process are studied by evaluation of the microstructure features (e.g., line width and height) as a function of time, particle type, and volume fraction. After assembly, the iron oxide particles are cross-linked in situ and subsequently released by dissolving a sacrificial layer. The free-floating magnetic structures are shown to retain their patterned shape during manipulation with external magnetic fields.

Ferrohydrodynamic modeling of magnetic nanoparticle harmonic spectra for magnetic particle imaging

Magnetic Particle Imaging (MPI) is an emerging imaging technique that uses magnetic nanoparticles as tracers. In order to analyze the quality of nanoparticles developed for MPI, a Magnetic Particle Spectrometer (MPS) is often employed. In this paper, we describe results for predictions of the nanoparticle harmonic spectra obtained in a MPS using three models: the first uses the Langevin function, which does not take into account finite magnetic relaxation; the second model uses the magnetization equation by Shliomis (Sh), which takes into account finite magnetic relaxation using a constant characteristic time scale; and the third model uses the magnetization equation derived by Martsenyuk, Raikher, and Shliomis (MRSh), which takes into account the effect of magnetic field magnitude on the magnetic relaxation time. We make comparisons between these models and with experiments in order to illustrate the effects of field-dependent relaxation in the MPS. The models results suggest that finite relaxation results in a significant drop in signal intensity (magnitude of individual harmonics) and in faster spectral decay. Interestingly, when field dependence of the magnetic relaxation time was taken into account, through the MRSh model, the simulations predict a significant improvement in the performance of the nanoparticles, as compared to the performance predicted by the Sh equation. The comparison between the predictions from models and experimental measurements showed excellent qualitative as well as quantitative agreement up to the 19th harmonic using the Sh and MRSh equations, highlighting the potential of ferrohydrodynamic modeling in MPI.

From oleic acid-capped iron oxide nanoparticles to polyethyleneimine-coated single-particle magnetofectins

Various inorganic nanoparticle designs have been developed and used as non-viral gene carriers. Magnetic gene carriers containing polyethyleneimine (PEI), a well-known transfection agent, have been shown to improve DNA transfection speed and efficiency in the presence of applied magnetic field gradients that promote particle–cell interactions. Here we report a method to prepare iron oxide nanoparticles conjugated with PEI that: preserves the narrow size distribution of the nanoparticles, conserves magnetic properties throughout the process, and results in efficient transfection. We demonstrate the ability of the particles to electrostatically bind with DNA and transfect human cervical cancer (HeLa) cells by the use of an oscillating magnet array. Their transfection efficiency is similar to that of Lipofectamine 2000™, a commercial transfection reagent. PEI-coated particles were subjected to acidification, and acidification in the presence of salts, before DNA binding. Results show that although these pre-treatments did not affect the ability of particles to bind DNA they did significantly enhanced transfection efficiency. Finally, we show that these magnetofectins (PEI-MNP/DNA) complexes have no effect on the viability of cells at the concentrations used in the study. The systematic preparation of magnetic vectors with uniform physical and magnetic properties is critical to progressing this non-viral transfection technology.

Collection of magnetic particles from synovial fluid using Nd-Fe-B micromagnets

In this paper, the collection of magnetic particles from synovial fluid using Nd-Fe-B micromagnets is quantitatively studied to determine the influence of fluid viscosity and magnet geometry on the velocity distribution and collection rate. Magnetic capture is validated in highly viscous fluids, such as bovine synovial fluid (η~ 1 Pa·s). A first-order theoretical model has been developed to predict the particle motion, as well as a numerical multiphysics model. Both models exhibit good agreement with in vitro experimental magnetic collection results. The velocity of the magnetic particles is shown to be inversely proportional to fluid viscosity, and two magnetic structures are compared in term of collection efficiency: a cylindrical Nd-Fe-B permanent magnet and a laser-machined conical Nd-Fe-B permanent magnet.

In situ measurements of dispersed and continuous phase viscosities of emulsions using nanoparticles.

The dynamic magnetic susceptibility response of magnetic nanoparticles was used to independently determine the viscosity of the dispersed and continuous phases of oil-in-water emulsions in situ. Cobalt ferrite nanoparticles coated with oleic acid (OA) or poly(ethylene glycol) (PEG) were prepared and mixed with emulsions, where they partitioned to the dispersed oil phase or continuous water phase, respectively. Emulsions with a range of dispersed-phase volume fractions were prepared and characterized using the nanoparticles and conventional rheometry. Conventional rheometry showed the expected increase in emulsion viscosity with increasing volume fraction of the dispersed oil phase. In contrast, the viscosity felt by the oleic acid coated nanoparticles partitioned to the dispersed oil phase was found to be independent of the volume fraction of the discontinuous phase and quantitatively similar to the bulk phase viscosity of mineral oil. Similarly, the viscosity felt by the PEG coated nanoparticles dispersed in the continuous water phase was also found to be independent of the volume fraction of the dispersed oil phase and quantitatively similar to the bulk viscosity of water. These results demonstrate how magnetic nanoparticles can be used to directly characterize the viscosity of the dispersed and continuous phases of emulsions in situ.

Design and validation of magnetic particle spectrometer for characterization of magnetic nanoparticle relaxation dynamics

The design and validation of a magnetic particle spectrometer (MPS) system used to study the linear and nonlinear behavior of magnetic nanoparticle suspensions is presented. The MPS characterizes the suspension dynamic response, both due to relaxation and saturation effects, which depends on the magnetic particles and their environment. The system applies sinusoidal excitation magnetic fields varying in amplitude and frequency and can be configured for linear measurements (1 mT at up to 120 kHz) and nonlinear measurements (50 mT at up to 24 kHz). Time-resolved data acquisition at up to 4 MS/s combined with hardware and software-based signal processing allows for wide-band measurements up to 50 harmonics in nonlinear mode. By cross-calibrating the instrument with a known sample, the instantaneous sample magnetization can be quantitatively reconstructed. Validation of the two MPS modes are performed for iron oxide and cobalt ferrite suspensions, exhibiting Néel and Brownian relaxation, respectively.

Magnetic Characterization of Iron Oxide Nanoparticles for Biomedical Applications

Iron oxide nanoparticles are of interest in a wide range of biomedical applications due to their response to applied magnetic fields and their unique magnetic properties. Magnetization measurements in constant and time-varying magnetic field are often carried out to quantify key properties of iron oxide nanoparticles. This chapter describes the importance of thorough magnetic characterization of iron oxide nanoparticles intended for use in biomedical applications. A basic introduction to relevant magnetic properties of iron oxide nanoparticles is given, followed by protocols and conditions used for measurement of magnetic properties, along with examples of data obtained from each measurement, and methods of data analysis.

Magnetic particle translation as a surrogate measure for synovial fluid mechanics

The mechanics of synovial fluid vary with disease progression, but are difficult to quantify quickly in a clinical setting due to small sample volumes. In this study, a novel technique to measure synovial fluid mechanics using magnetic nanoparticles is introduced. Briefly, microspheres embedded with superparamagnetic iron oxide nanoparticles, termed magnetic particles, are distributed through a 100μL synovial fluid sample. Then, a permanent magnet inside a protective sheath is inserted into the synovial fluid sample. Magnetic particles translate toward the permanent magnet and the percentage of magnetic particles collected by the magnet in a given time can be related to synovial fluid viscosity. To validate this relationship, magnetic particle translation was demonstrated in three phases. First, magnetic particle translation was assessed in glycerol solutions with known viscosities, demonstrating that as fluid viscosity increased, magnetic particle translation decreased. Next, the relationship between magnetic particle translation and synovial fluid viscosity was assessed using bovine synovial fluid that was progressively degenerated via ultrasonication. Here, particle collection in a given amount of time increased as fluid degenerated, demonstrating that the relationship between particle collection and fluid mechanics holds in non-Newtonian synovial fluid. Finally, magnetic particle translation was used to assess differences between healthy and OA affected joints in equine synovial fluid. Here, particle collection in a given time was higher in OA joints relative to healthy horses (p<0.001). Combined, these data demonstrate potential viability of magnetic particle translation in a clinical setting to evaluate synovial fluid mechanics in limited volumes of synovial fluid sample.

Fabrication of patterned magnetic microstructures using magnetically assembled nanoparticles

This work describes the modeling and experimental characterization of a fabrication method for forming magnetic microstructures using self-assembled iron oxide (Fe3O4) magnetic nanoparticles. This method can potentially be used in roll-to-roll production of magnetic structures patterned onto substrates or optionally lifted off to create free-floating micromagnetic actuators. This article reports: (1) the use of a selective magnetization process to create magnetic microstructures with complex, photolithographically defined shapes, (2) development of multi-physics simulations that model key fabrication steps (selective magnetization and particle assembly), and (3) experimental evaluation of the microstructure features (line width and height) as functions of process variables. The primary accomplishment is obtaining well-defined microstructures with complex shape and demonstrating their magnetic actuation when released as free-floating structures.