No abstract

Aerosol delivery via a mechanical ventilator remains unregulated with no standards for drug delivery to intubated patients. Bench models predicting drug delivery have not been validated in vivo. For modern ventilator designs, we chose to identify, on the bench, the most important variables affecting aerosol delivery and to correlate in vitro predictions of aerosol delivery with in vivo end points independent of patient response. Test aerosols of albuterol and antibiotics were compared. Bench measurements of inhaled mass (percentage of nebulizer charge, mean +/- SEM) ranged from 5.7 +/- 0.5% to 37.4 +/- 1.6%, with breath-actuated nebulization and humidity identified as the most important factors determining aerosol delivery. In patients, sputum levels of deposited antibiotics varied from 1.10 to 19.6 microg/ml/mg. Variation in sputum levels correlated with predictions from the in vitro model. Aerosol delivery in ventilated patients can be efficient and reproducible only if defined ventilator parameters are tightly controlled. Key parameters can be determined via in vitro bench testing defining delivery standards for clinical trials of drugs with narrow therapeutic/toxicity ratios.

A new solid-state, Al2O3 nanopore sensor with enhanced surface properties for the real-time detection and analysis of individual DNA molecules is reported. Nanopore formation using electron beam based decomposition transformed the local nanostructure and morphology of the pore from an amorphous, stoichiometric structure (O to Al ratio of 1.5) to a hetero-phase crystalline network, deficient in O (O to Al ratio of ~0.6). Direct metallization of the pore region was observed during irradiation, thereby permitting the potential fabrication of nano-scale metallic contacts in the pore region with potential application to nanopore-based DNA sequencing. Dose dependent phase transformations to purely γ and/or α-phase nanocrystallites were also observed during pore formation allowing for surface charge engineering at the nanopore/fluid interface. DNA transport studies revealed an order of magnitude reduction in translocation velocities relative to alternate solid-state architectures, accredited to high surface charge density and the nucleation of charged nanocrystalline domains. The unique surface properties of Al2O3 nanopore sensors makes them ideal for the detection and analysis of ssDNA, dsDNA, RNA secondary structures and small proteins. These nano-scale sensors may also serve as a useful tool in studying the mechanisms driving biological processes including DNA-protein interactions and enzyme activity at the single molecule level.

Geometry and confinement effects at the nanoscale can result in substantial modifications to a material's properties with significant consequences in terms of chemical reactivity, biocompatibility and toxicity. Although benefiting applications across a diverse array of environmental and technological settings, the long-term effects of these changes, for example in the reaction of metallic nanoparticles under atmospheric conditions, are not well understood. Here, we use the unprecedented resolution attainable with aberration-corrected scanning transmission electron microscopy to study the oxidation of cuboid Fe nanoparticles. Performing strain analysis at the atomic level, we reveal that strain gradients induced in the confined oxide shell by the nanoparticle geometry enhance the transport of diffusing species, ultimately driving oxide domain formation and the shape evolution of the particle. We conjecture that such a strain-gradient-enhanced mass transport mechanism may prove essential for understanding the reaction of nanoparticles with gases in general, and for providing deeper insight into ionic conductivity in strained nanostructures.

Polarized neutron reflectivity measurements of a ferromagnetic [(LaMnO3)11.8/(SrMnO3)4.4]6 superlattice reveal a modulated magnetic structure with an enhanced magnetization at the interfaces where LaMnO3 was deposited on SrMnO3 (LMO/SMO). However, the opposite interfaces (SMO/LMO) are found to have a reduced ferromagnetic moment. The magnetic asymmetry arises from the difference in lateral structural roughness of the two interfaces observed via electron microscopy, with strong ferromagnetism present at the interfaces that are atomically smooth over tens of nanometers. This result demonstrates that atomic-scale roughness can destabilize interfacial phases in complex oxide heterostructures.