Characterizing the adsorption of proteins on glass capillary surfaces using electrospray-differential mobility analysis

We quantify the adsorption and desorption of a monoclonal immunoglobulin-G antibody, rituxamab (RmAb), on silica capillary surfaces using electrospray-differential mobility analysis (ES-DMA). We first develop a theory to calculate coverages and desorption rate constants from the ES-DMA data for proteins adsorbing on glass capillaries used to electrospray protein solutions. This model is then used to study the adsorption of RmAb on a bare silica capillary surface. A concentration-independent coverage of ≈4.0 mg/m(2) is found for RmAb concentrations ranging from 0.01 to 0.1 mg/mL. A study of RmAb adsorption to bare silica as a function of pH shows maximum adsorption at its isoelectric point (pI of pH 8.5) consistent with literature. The desorption rate constants are determined to be ≈10(-5) s(-1), consistent with previously reported values, thus suggesting that shear forces in the capillary may not have a considerable effect on desorption. We anticipate that this study will allow ES-DMA to be used as a "label-free" tool to study adsorption of oligomeric and multicomponent protein systems onto fused silica as well as other surface modifications.     

Hydrodynamic fractionation of finite size gold nanoparticle clusters

We demonstrate a high-resolution in situ experimental method for performing simultaneous size classification and characterization of functional gold nanoparticle clusters (GNCs) based on asymmetric-flow field flow fractionation (AFFF). Field emission scanning electron microscopy, atomic force microscopy, multi-angle light scattering (MALS), and in situ ultraviolet-visible optical spectroscopy provide complementary data and imagery confirming the cluster state (e.g., dimer, trimer, tetramer), packing structure, and purity of fractionated populations. An orthogonal analysis of GNC size distributions is obtained using electrospray-differential mobility analysis (ES-DMA). We find a linear correlation between the normalized MALS intensity (measured during AFFF elution) and the corresponding number concentration (measured by ES-DMA), establishing the capacity for AFFF to quantify the absolute number concentration of GNCs. The results and corresponding methodology summarized here provide the proof of concept for general applications involving the formation, isolation, and in situ analysis of both functional and adventitious nanoparticle clusters of finite size.     

Characterizing the coating and size-resolved oxidative stability of carbon-coated aluminum nanoparticles by single-particle mass-spectrometry

Aluminum nanoparticles are of significant interest in enhancing the rate of energy release from propellants. One of the major impediments to their use is that bare aluminum is highly reactive, while oxide coated aluminum significantly decreases overall performance. We investigate creating aluminum nanoparticles with a thin carbon coating using either a laser induced plasma or a DC plasma-arc. The carbon coating was created by injecting ethylene (C₂H₄) directly downstream of the plasma. The elemental composition of the coated aluminum nanoparticles was measured in real time with a recently developed quantitative single particle mass spectrometer (SPMS). We found that the aluminum nanoparticles were coated with a carbon layer of thickness around 1–3 nm.The thermal and oxidative stability of these particles was determined by passing the aerosols through a heated flow reactor in a carrier flow of either air or argon, and measuring the aluminum, carbon and oxygen content in the particles with the single particle mass spectrometer. We found that below 700°C the coating was stable, but that the coating oxidized above ∼ ∼800°C. In contrast the carbon coating was thermally stable above ∼ ∼900°C. These results indicate that a carbon coating may be a suitable passivating agent.     

Understanding the mechanism of aluminium nanoparticle oxidation

Aluminium nanoparticles have gained importance in the last decade because of their increased reactivity as compared with traditional micron-sized particle. The physics of burning of aluminium nanoparticle is expected to be different than that of micron-sized particles, and the current article is motivated by these differences. We have previously measured the size resolved reactivity of nanoaluminium by single-particle mass spectrometry, to which we now add transmission electron microscope (TEM) and an on-line density measurement. The latter two studies revealed the presence of hollow particles following oxidation of nanoaluminium and indicating the significance of diffusion of aluminium in the overall process. Based on experimental evidence, we believe that aluminium nanoparticle oxidation occurs in two regimes. Prior to melting of aluminium slow oxidation occurs through the diffusion of oxygen through the aluminium oxide shell. Above the melting point, we transition to a fast oxidation regime whereby both aluminium and oxygen diffuse through the oxide shell to enhance the oxidation rate.

We also develop a phenomenological model for nanoaluminium oxidation that accounts for the experimentally observed rates, the fact that both fuel and oxidizer are diffusing, and a new effect related to internal pressure gradients. The latter phenomen is based on molecular dynamic simulations suggesting that there are large pressure gradients present inside these particles, with the aluminium core under a positive pressure and the aluminium oxide shell under a negative pressure. We have considered the effect of these pressure gradients on the oxidation process. A power law relation was obtained (t ∝ r ^{1.6± 0.1}) between the time required for oxidation and particle radius.     

An Unexpected Role of Hyaluronic Acid in Trafficking siRNA Across the Cellular Barrier: The First Biomimetic,Anionic, Non‐Viral Transfection Method

Circulating nucleic acids, such as short interfering RNA (siRNA), regulate many biological processes; however, the mechanism by which these molecules enter the cell is poorly understood. The role of extracellular‐matrix‐derived polymers in binding siRNAs and trafficking them across the plasma membrane is reported. Thermal melting, dynamic light scattering, scanning electron microscopy, and computational analysis indicate that hyaluronic acid can stabilize siRNA via hydrogen bonding and Van der Waals interactions. This stabilization facilitated HA size‐ and concentration‐dependent gene silencing in a CD44‐positive human osteosarcoma cell line (MG‐63) and in human mesenchymal stromal cells (hMSCs). This native HA‐based siRNA transfection represents the first report on an anionic, non‐viral delivery method that resulted in approximately 60 % gene knockdown in both cell types tested, which correlated with a reduction in translation levels.     

Insights into the Mechanism and Catalysis of Oxime Coupling Chemistry at Physiological pH

The dynamic covalent‐coupling reaction involving α‐effect nucleophiles has revolutionized bioconjugation approaches, due to its ease and high efficiency. Key to its success is the discovery of aniline as a nucleophilic catalyst, which made this reaction feasible under physiological conditions. Aniline however, is not so effective for keto substrates. Here, we investigate the mechanism of aniline activation in the oxime reaction with aldehyde and keto substrates. We also present carboxylates as activating agents that can promote the oxime reaction with both aldehyde and keto substrates at physiological pH. This rate enhancement circumvents the influence of α‐effect by forming H‐bonds with the rate‐limiting intermediate, which drives the reaction to completion. The combination of aniline and carboxylates had a synergistic effect, resulting in a ～14–31‐fold increase in reaction rate at pD 7.4 with keto substrates. The biocompatibility and efficiency of carboxylate as an activating agent is demonstrated by performing cell‐surface oxime labeling at physiological pH using acetate, which showed promising results that were comparable with aniline.     

"Effective" negative surface tension: a property of coated nanoaerosols relevant to the atmosphere

Atmospheric aerosols play a very important role in atmospheric processes and have a major influence on the global climate. In this paper, we report results of a molecular dynamics study on the unique properties of organic-coated water droplets. In particular, we find that, for particles preferring an inverted micelle structure, the lower chain-chain interaction, with increasing radial distance from the water-organic interface, results in a negative internal radial pressure profile for the organic layer. As a result, a coated particle behaves as though the surface tension is "negative" and implies that such a particle will inherently have an inverse Kelvin vapor pressure effect, resulting in increased water condensation.     

Measurement of Inherent Material Density of Nanoparticle Agglomerates

We describe a new technique to measure the size dependent inherent material density of chain agglomerate particles. Measurements were carried out for diesel soot and aluminum/alumina agglomerate particles in the nanometer size range. Transmission electron microscopy was used to measure the volumes of agglomerate particles that were preselected by mass using an aerosol particle mass analyzer. We found that the density of diesel exhaust particles increased from 1.27 to 1.78g/cm³ as particle mobility size increased from 50 to 220nm. When particles are preheated to remove volatile components, the density was 1.77±0.07g/cm³, independent of particle size. The densities measured after heating correspond to the inherent material density of diesel soot. Measurements with aluminum nanoparticles were made downstream of a furnace where aluminum (Al) was converted to alumina (Al₂O₃). From measurements of inherent material density we were able to infer the extent of reaction, which varied with furnace temperature.     

Metal-free aromatic hydrogenation: aniline to cyclohexyl-amine derivatives

Hydrogenation of the N-bound phenyl rings of amines, imines, and aziridine is achieved in the presence of H(2) and B(C(6)F(5))(3), affording the corresponding N-cyclohexylammonium hydridoborate salts.     

Detecting cortical lesions in multiple sclerosis at 7 T using white matter signal attenuation

Cortical lesions have recently been a focus of multiple sclerosis (MS) MR research. In this study, we present a white matter signal attenuating sequence optimized for cortical lesion detection at 7 T. The feasibility of white matter attenuation (WHAT) for cortical lesion detection was determined by scanning eight patients (four relapsing/remitting MS, four secondary progressive MS) at 7 T. WHAT showed excellent gray matter-white matter contrast, and cortical lesions were hyperintense to the surrounding cortical gray matter, The sequence was then optimized for cortical lesion detection by determining the set of sequence parameters that produced the best gray matter-cortical lesion contrast in a 10-min scan. Despite the B1 inhomogeneities common at ultra-high field strengths, WHAT with an adiabatic inversion pulse showed good cortical lesion detection and would be a valuable component of clinical MS imaging protocols.