Robert C. Woodward

Current Sensing Techniques: A Review

This paper provides a thorough review of state-of-the-art current sensing techniques. It catalogues the current sensors according to the underlying physical principle in order to point out their strengths and weaknesses.

Anti-fouling magnetic nanoparticles for siRNA delivery

Iron oxide nanoparticles (IONPs), with a diameter of 8 nm, have been coated with two different polymers, i.e. poly(oligoethylene glycol) methyl ether acrylate (P(OEG-A)) and poly(dimethylaminoethyl acrylate) (P(DMAEA)). The polymers were attached to the nanoparticle surface using two different strategies, with the aim of creating an internal layer of P(DMAEA) and an outer shell of P(OEG-A). The subsequent polymer-stabilized IONPs were characterized using ATR, XPS and TGA, proving the presence of polymers on the IONP surfaces with a grafting density ranging from 0.05 to 0.22 chain per nm2. High grafting densities were demonstrated when the two homopolymers were assembled on the surfaces of the IONPs simultaneously. The polymer composition at the surfaces of the IONPs could be controlled by manipulating the feed ratio P(OEG-A)–P(DMAEA) present in solution. These hybrid organic–inorganic particles (70–150 nm) proved to be stable in both water and 50 vol% fetal bovine serum (FBS). In addition, zeta-potential measurements confirmed that P(OEG-A) chains effectively mask the positive charge originating from P(DMAEA) thereby limiting protein adsorption on these particles. Hybrid nanoparticles were exploited for the complexation of siRNA, thereby generating IONP siRNA nano-carriers with anti-fouling P(OEG-A) shells. The transfection efficiency was measured using human neuroblastoma SHEP cells both in the presence and in the absence of a magnetic field in FBS. The transfection efficiency was determined by both fluorescence microscopy and flow cytometry. Cytotoxicity studies revealed that the IONP carriers were non-toxic to SHEP cells. In addition, studies on the proton transverse relaxation enhancement properties of these stabilized IONPs indicated high relaxivities (∼160 s−1 per mM of Fe).

Experimental validation of proton transverse relaxivity models for superparamagnetic nanoparticle MRI contrast agents

Analytical models of proton transverse relaxation rate enhancement by magnetic nanoparticles were tested by making measurements on model experimental systems in a field of 1.4 T. Proton relaxivities were measured for five aqueous suspensions of iron oxide (maghemite) nanoparticles with nominal mean particle sizes of 6, 8, 10, 11, and 13 nm. Proton relaxivity increased with mean particle size ranging from 13 s(-1) mM Fe(-1) for the 6 nm sample, up to 254 s(-1) mM Fe(-1) for the 13 nm sample. A strong correlation between the measured and predicted values of the relaxivity was observed, with the predicted values being consistently higher than the measured values. The results indicate that the models give a reasonable agreement with experimental results and hence can be used as the basis for the design of new magnetic resonance imaging contrast and labelling agents.

Insight into serum protein interactions with functionalized magnetic nanoparticles in biological media.

Surface modification with linear polymethacrylic acid (20 kDa), linear and branched polyethylenimine (25 kDa), and branched oligoethylenimine (800 Da) is commonly used to improve the function of magnetite nanoparticles (MNPs) in many biomedical applications. These polymers were shown herein to have different adsorption capacity and anticipated conformations on the surface of MNPs due to differences in their functional groups, architectures, and molecular weight. This in turn affects the interaction of MNPs surfaces with biological serum proteins (fetal bovine serum). MNPs coated with 25 kDa branched polyethylenimine were found to attract the highest amount of serum protein while MNPs coated with 20 kDa linear polymethacrylic acid adsorbed the least. The type and amount of protein adsorbed, and the surface conformation of the polymer was shown to affect the size stability of the MNPs in a model biological media (RPMI-1640). A moderate reduction in r(2) relaxivity was also observed for MNPs suspended in RPMI-1640 containing serum protein compared to the same particles suspended in water. However, the relaxivities following protein adsorption are still relatively high making the use of these polymer-coated MNPs as Magnetic Resonance Imaging (MRI) contrast agents feasible. This work shows that through judicious selection of functionalization polymers and elucidation of the factors governing the stabilization mechanism, the design of nanoparticles for applications in biologically relevant conditions can be improved.

Toward Design of Magnetic Nanoparticle Clusters Stabilized by Biocompatible Diblock Copolymers for T2-Weighted MRI Contrast

We report the fabrication of magnetic particles comprised of clusters of iron oxide nanoparticles, 7.4 nm mean diameter, stabilized by a biocompatible, amphiphilic diblock copolymer, poly(ethylene oxide-b-D,L-lactide). Particles with quantitative incorporation of up to 40 wt % iron oxide and hydrodynamic sizes in the range of 80-170 nm were prepared. The particles consist of hydrophobically modified iron oxide nanoparticles within the core-forming polylactide block with the poly(ethylene oxide) forming a corona to afford aqueous dispersibility. The transverse relaxivities (r2) increased with average particle size and exceeded 200 s(-1) mM Fe(-1) at 1.4 T and 37 °C for iron oxide loadings above 30 wt %. These experimental relaxivities typically agreed to within 15% with the values predicted using analytical models of transverse relaxivity and cluster (particle core) size distributions derived from cryo-TEM measurements. Our results show that the theoretical models can be used for the rational design of biocompatible MRI contrast agents with tailored compositions and size distributions.

The effect of polymer coatings on proton transverse relaxivities of aqueous suspensions of magnetic nanoparticles

Iron oxide magnetic nanoparticles are good candidates for magnetic resonance imaging (MRI) contrast agents due to their high magnetic susceptibilities. Here we investigate 19 polyether-coated magnetite nanoparticle systems comprising three series. All systems were synthesized from the same batch of magnetite nanoparticles. A different polyether was used for each series. Each series comprised systems with systematically varied polyether loadings per particle. A highly significant (p < 0.0001) linear correlation (r = 0.956) was found between the proton relaxivity and the intensity-weighted average diameter measured by dynamic light scattering in the 19 particle systems studied. The intensity-weighted average diameter measured by dynamic light scattering is sensitive to small number fractions of larger particles/aggregates. We conclude that the primary effect leading to differences in proton relaxivity between systems arises from the small degree of aggregation within the samples, which appears to be determined by the nature of the polymer and, for one system, the degree of polymer loading of the particles. For the polyether coatings used in this study, any changes in relaxivity from differences in water exclusion or diffusion rates caused by the polymer are minor in comparison with the changes in relaxivity resulting from variations in the degree of aggregation.

Lanthanoid “Bottlebrush” Clusters: Remarkably Elongated Metal–Oxo Core Structures with Controllable Lengths

Large metal-oxo clusters consistently assume spherical or regular polyhedral morphologies rather than high-aspect-ratio structures. Access to elongated core structures has now been achieved by the reaction of lanthanoid salts with a tetrazole-functionalized calixarene in the presence of a simple carboxylate co-ligand. The resulting Ln19 and Ln12 clusters are constructed from apex-fused Ln5O6 trigonal bipyramids and are formed consistently under a range of reaction conditions and reagent ratios. Altering the carboxylate co-ligand structure reliably controls the cluster length, giving access to a new class of rod-like clusters of variable length.

Magnetic particle-mediated magnetoreception

Behavioural studies underpin the weight of experimental evidence for the existence of a magnetic sense in animals. In contrast, studies aimed at understanding the mechanistic basis of magnetoreception by determining the anatomical location, structure and function of sensory cells have been inconclusive. In this review, studies attempting to demonstrate the existence of a magnetoreceptor based on the principles of the magnetite hypothesis are examined. Specific attention is given to the range of techniques, and main animal model systems that have been used in the search for magnetite particulates. Anatomical location/cell rarity and composition are identified as two key obstacles that must be addressed in order to make progress in locating and characterizing a magnetite-based magnetoreceptor cell. Avenues for further study are suggested, including the need for novel experimental, correlative, multimodal and multidisciplinary approaches. The aim of this review is to inspire new efforts towards understanding the cellular basis of magnetoreception in animals, which will in turn inform a new era of behavioural research based on first principles.

Sensing magnetic nanoparticles using nano-confined ferromagnetic resonances in a magnonic crystal

We experimentally demonstrate the use of the magnetic-field-dependence of highly spatially confined, GHz-frequency ferromagnetic resonances for the detection of magnetic nanoparticles using an anti-dot-based magnonic crystal. The stray magnetic fields of nanoparticles within the anti-dots modify nano-confined ferromagnetic resonances in the surrounding periodically nanopatterned magnonic crystal, generating easily measurable resonance peak shifts. The shifts are comparable to the resonance linewidths for high anti-dot filling fractions with their signs and magnitudes dependent upon the mode localization, consistent with micromagnetic simulation results. This is an encouraging result for the development of frequency-based nanoparticle detectors for nano-scale biosensing.

Variability and consistency in lung inflammatory responses to particles with a geogenic origin.

Particulate matter <10 μm (PM10) is well recognized as being an important driver of respiratory health; however, the impact of PM10 of geogenic origin on inflammatory responses in the lung is poorly understood. This study aimed to assess the lung inflammatory response to community sampled geogenic PM10.