The influence of interparticle cohesion on rebounding slow impacts on rubble pile asteroids.

The ballistic sorting effect has been proposed to be a driver behind the observed size sorting on the rubble pile asteroid Itokawa. This effect depends on the inelasticity of slow collisions with granular materials. The inelasticity of a collision with a granular material, in turn, depends on grain size. Here we argue that determining the inelasticity of such collisions in an asteroid-like environment is a nontrivial task. We show non-monotonic dependency of the coefficient of restitution (COR) on target particle size using experiments in microgravity. Employing numerical simulations, we explain these results with the growing influence of adhesion for smaller-sized particles. We conclude that there exists an optimum impactor to target particle size ratio for ballistic sorting.

Assessing the Immunomodulatory Effect of Size on the Uptake and Immunogenicity of Influenza- and Hepatitis B Subunit Vaccines In Vitro.

Viral subunit vaccines are a safer and more tolerable alternative to whole inactivated virus vaccines. However, they often come with limited efficacy, necessitating the use of adjuvants. Using free and particle-bound viral antigens, we assessed whether size affects the uptake of those antigens by human monocyte-derived dendritic cells (Mo-DCs) and whether differences in uptake affect their capacity to stimulate cytokine production by T cells. To this end, influenza antigens and hepatitis B surface antigen (HBsAg) were covalently conjugated to polystyrene particles of 500 nm and 3 µm. Cellular uptake of the antigens, either unconjugated or conjugated, and their capacity to stimulate T cells within a population of human peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry. Conjugation of both antigens to particles significantly increased their uptake by Mo-DCs. Moreover, both the 500 nm and 3 µm influenza conjugates induced significantly higher numbers of cytokine-producing CD4+ T cells and induced increased production of the pro-inflammatory cytokines IFNγ and TNFα. In contrast, conjugation of HBsAg to particles did not notably affect the T cell response. In conclusion, conjugation of antigen to 500 nm and 3 µm particles leads to increased antigen uptake by human Mo-DCs, although the capacity of such conjugates to induce T cell stimulation likely depends on the immunological status of the PBMC donor.

Dynamic light scattering from single macroscopic particles.

Here we present a methodology to characterize the light intensity fluctuations that arise from rotations of individual granular particles. We describe a setup for dynamic light scattering measurements on individual macroscopic particles and isolate the contribution from rotations of the individual particles to the obtained correlation functions. The results show that rotation of granular particles results in a significant contribution to scattered light intensity fluctuations, a phenomenon not considered so far in dynamic light scattering measurements on fluidized granular media. The results presented here may thus form the basis for an extended light scattering methodology for granular media, and improve the selection of granular particles according to their dynamic light scattering signal.

A PBMC-Based System to Assess Human T Cell Responses to Influenza Vaccine Candidates In Vitro.

Vaccine development is an expensive and time-consuming process that heavily relies on animal models. Yet, vaccine candidates that have previously succeeded in animal experiments often fail in clinical trials questioning the predictive value of animal models. Alternative assay systems that can add to the screening and evaluation of functional characteristics of vaccines in a human context before embarking on costly clinical trials are therefore urgently needed. In this study, we have established an in vitro system consisting of long-term cultures of unfractionated peripheral blood mononuclear cells (PBMCs) from healthy volunteers to assess (recall) T cell responses to vaccine candidates. We observed that different types of influenza vaccines (whole inactivated virus (WIV), split, and peptide vaccines) were all able to stimulate CD4 and CD8 T cell responses but to different extents in line with their reported in vivo properties. In-depth analyses of different T cell subsets revealed that the tested vaccines evoked mainly recall responses as indicated by the fact that the vast majority of the responding T cells had a memory phenotype. Furthermore, we observed vaccine-induced activation of T follicular helper cells, which are associated with the induction of humoral immune responses. Our results demonstrate the suitability of the established PBMC-based system for the in vitro evaluation of memory T cell responses to vaccines and the comparison of vaccine candidates in a human immune cell context. As such, it can help to bridge the gap between animal experiments and clinical trials and assist in the selection of promising vaccine candidates, at least for recall antigens.

Distinguishing noisy crystalline structures using bond orientational order parameters.

The bond orientational order parameters originally introduced by Steinhardt et al. (Phys. Rev. B 28, 784 (1983)) are a common tool for local structure characterization in soft matter studies. Recently, Mickel et al. (J. Chem. Phys. 138, 044501 (2013)) highlighted problems of the bond orientational order parameters due to the ambiguity of the underlying neighbourhood definition. Here we show the difficulties to distinguish common structures like FCC- and BCC-based structures with the suggested neighbourhood definitions when noise is introduced. We propose a simple improvement to the neighbourhood definition that results in robust and continuous bond orientational order parameters with which we can accurately distinguish crystal structures even when noise is present.

Granular ionic crystals in a small nutshell.

Ordered two-dimensional arrangements of triboelectrically oppositely charged granular particles have been reported several times, but observations of bulk ordered binary granular particle packings are singular. We attribute this suppression of triboelectrically induced order to the concurrent behaviour of granular particles to pack densest due to gravity. We show that triboelectrically induced order robustly emerges in a container that does not allow for crystallization into a dense packing under gravity. It turns out that the triboelectrically ordered structure follows Pauling's predictions for atomic ionic crystals in many aspects, but also exhibits systematic deviations. We discuss how the emergence of order in an incommensurate container, the deviations from Pauling's predictions and the gravitational potential energy of the particles are connected.

The mechanism behind the biphasic pulsatile drug release from physically mixed poly(dl-lactic(-co-glycolic) acid)-based compacts.

Successful immunization often requires a primer, and after a certain lag time, a booster administration of the antigen. To improve the vaccinees' comfort and compliance, a single-injection vaccine formulation with a biphasic pulsatile release would be preferable. Previous work has shown that such a release profile can be obtained with compacts prepared from physical mixtures of various poly(dl-lactic(-co-glycolic) acid) types (Murakami et al., 2000). However, the mechanism behind this release profile is not fully understood. In the present study, the mechanism that leads to this biphasic pulsatile release was investigated by studying the effect of the glass transition temperature (Tg) of the polymer, the temperature of compaction, the compression force, the temperature of the release medium, and the molecular weight of the incorporated drug on the release behavior. Compaction resulted in a porous compact. Once immersed into release medium with a temperature above the Tg of the polymer, the drug was released by diffusion through the pores. Simultaneously, the polymer underwent a transition from the glassy state into the rubbery state. The pores were gradually closed by viscous flow of the polymer and further release was inhibited. After a certain period of time, the polymer matrix ruptured, possibly due to a build-up in osmotic pressure, resulting in a pulsatile release of the remaining amount of drug. The compression force and the molecular weight of the incorporated drug did not influence the release profile. Understanding this mechanism could contribute to further develop single-injection vaccines.

Ovalbumin-containing core-shell implants suitable to obtain a delayed IgG1 antibody response in support of a biphasic pulsatile release profile in mice.

A single-injection vaccine formulation that provides for both a prime and a boost immunization would have various advantages over a multiple-injection regime. For such a vaccine formulation, it is essential that the booster dose is released after a certain, preferably adjustable, lag time. In this study we investigated whether a core-shell based implant, containing ovalbumin as core material and poly(DL-lactic-co-glycolic acid) of various monomer ratios as shell material can be used to obtain such a booster release. An in vitro release study showed that the lag time after which the ovalbumin was released from the core-shell implant increased with increasing lactic to glycolic acid ratio of the polymer and ranged from 3-6 weeks. Fluorescence spectroscopy showed minimal differences between native ovalbumin and ovalbumin from core-shell implants that were incubated until just before the observed in vitro release. In addition, mice immunized with a subcutaneous inserted core-shell implant containing ovalbumin showed an ovalbumin-specific IgG1 antibody response after a lag time of 4 or 6-8 weeks. Moreover, delayed release of ovalbumin caused higher IgG1 antibody titers than conventional subcutaneous vaccination with ovalbumin dissolved in PBS. Collectively, these findings could contribute to the further development of a single-injection vaccine, making multiple injections of the vaccine superfluous.

Double origin of stochastic granular tribocharging.

The mechanisms underlying triboelectric charging have a stochastic nature. We investigate how this randomness affects the distributions of charges generated on granular particles during either a single or many collisions. The charge distributions we find in our experiments are more heavy-tailed than normal distributions with an exponential decay of the probability, they are asymmetric, and exhibit charges of both signs. Moreover, we find a linear correlation between the width and mean of these distributions. We rationalize these findings with a model for triboelectric charging which combines stochastic charge separation during contact and stochastic charge recombination after separation of the surfaces. Our results further imply that subsequent charging events are not statistically independent.

Dense fluidized granular media in microgravity.

Handling and transport of granular media are inevitably governed by the settling of particles. Settling into a dense state is one of the defining characteristics of granular media, among dissipation and absence of thermal agitation. Hence, settling complicates the adaptation of microscopic theories from atomic, molecular, or colloidal media to granular media. It is desirable to provide experiments in which selectively one of the granular characteristics is tuned to test suitable adaptation of a theory. Here we show that gas fluidization of granular media in microgravity is a suitable approach to achieve steady states closer to thermally agitated systems free of settling. We use diffusing-wave spectroscopy to compare the spatial homogeneity and the microscopic dynamics of gas-fluidized granular media on the ground and in drop tower flights with increasing packing densities up to full arrest. The gas fluidization on the ground leads to inhomogeneous states as known from fluidized beds, and partial arrest occurs at packing fractions lower than the full arrested packing. The granular medium in microgravity in contrast attains a homogeneous state with complete mobilization even close to full arrest. Fluidized granular media thus can be studied in microgravity with dynamics and packing fractions not achievable on the ground.

Analysis of granular packing structure by scattering of THz radiation.

Scattering methods are widely used to characterize the structure and constituents of matter on small length scales. This motivates this introductory text on identifying prospective approaches to scattering-based methods for granular media. A survey to light scattering by particles and particle ensembles is given. It is elaborated why the established scattering methods using X-rays and visible light cannot in general be transferred to granular media. Spectroscopic measurements using terahertz radiation are highlighted as they probe the scattering properties of granular media, which are sensitive to the packing structure. Experimental details to optimize a spectrometer for measurements on granular media are discussed. We perform transmission measurements on static and agitated granular media using Fourier transform spectroscopy at the THz beamline of the Bessy II storage ring. The measurements demonstrate the potential to evaluate degrees of order in the media and to track transient structural states in agitated bulk granular media.

Probing density waves in fluidized granular media with diffusing-wave spectroscopy.

Density waves are characteristic for fluidized beds and affect measurements on liquidlike dynamics in fluidized granular media. Here the intensity autocorrelation function as obtainable with diffusing-wave spectroscopy is derived in the presence of density waves. The predictions by the derived form of the intensity autocorrelation function match experimental observations from a gas-fluidized bed. The model suggests separability of the contribution from density waves from the contribution by microscopic scatterer displacement to the decay of correlation and thus paves the way for characterizing microscopic particle motions using diffusing-wave spectroscopy as well as heterogeneities in fluidized granular media.

Dry influenza vaccines: towards a stable, effective and convenient alternative to conventional parenteral influenza vaccination.

Cold-chain requirements, limited stockpiling potential and the lack of potent immune responses are major challenges of parenterally formulated influenza vaccines. Decreased cold chain dependence and stockpiling can be achieved if vaccines are formulated in a dry state using suitable excipients and drying technologies. Furthermore, having the vaccine in a dry state enables the development of non-parenteral patient friendly dosage forms: microneedles for transdermal administration, tablets for oral administration, and powders for epidermal, nasal or pulmonary administration. Moreover, these administration routes have the potential to elicit an improved immune response. This review highlights the rationale for the development of dried influenza vaccines, as well as processes used for the drying and stabilization of influenza vaccines; it also compares the immunogenicity of dried influenza vaccines administered via non-invasive routes with that of parenterally administered influenza vaccines. Finally, it discusses unmet needs, challenges and future developments in the field of dried influenza vaccines.

Self-assembly of gold nanoparticles at the oil-vapor interface: from mono- to multilayers.

Alkylthiol-coated gold nanoparticles spontaneously segregate from dispersion in toluene to the toluene-vapor interface. We show that surface tension drops during segregation with a rate that depends on particle concentration. Mono- and multilayers of particles form depending on particle concentration, time, and temperature. X-ray reflectometry indicates fast monolayer formation and slow multilayer formation. A model that combines diffusion-limited segregation driven by surface energy and heterogeneous agglomeration driven by dispersive van der Waals particle interactions is proposed to describe film formation.

Ligand-dominated temperature dependence of agglomeration kinetics and morphology in alkyl-thiol-coated gold nanoparticles.

The stability of nanoparticle suspensions and the details of their agglomeration depend on the interactions between particles. We study this relationship in gold nanoparticles stabilized with different alkyl thiols in heptane. Temperature-dependent interactions were inferred from small-angle x-ray scattering, agglomeration kinetics from dynamic light scattering, and agglomerate morphologies from transmission electron microscopy. We find that the particles precipitate at temperatures below the melting temperatures of the dry ligands. Agglomerates grow with rates that depend on the temperature: Around precipitation temperature, globular agglomerates form slowly, while at lower temperatures, fibrilar agglomerates form rapidly. All agglomerates contain random dense packings rather than crystalline superlattices. We conclude that ligand-ligand and ligand-solvent interactions of the individual particles dominate suspension stability and agglomeration kinetics. The microscopic packing is dominated by interactions between the ligands of different nanoparticles.

Switching between crystallization and amorphous agglomeration of alkyl thiol-coated gold nanoparticles.

Crystalline and amorphous materials composed of the same atoms exhibit strikingly different properties. Likewise, the behavior of materials composed of mesoscale particles depends on the arrangement of their constituent particles. Here, we demonstrate control over particle arrangement during agglomeration. We obtain disordered and ordered agglomerates of the same alkyl thiol-coated gold nanoparticles depending on temperature and solvent. We find that ordered agglomeration occurs exclusively above the melting temperature of the ligand shells. Many-particle simulations show that the contact mechanics of the ligand shells dominate the order-disorder transition: Purely spherical particle-particle interactions yield order, whereas localized "stiction" between the ligand shells leads to disorder. This indicates that the "stickiness" and the packing of the agglomerates can be switched by the state of the ligand shells. It suggests that contact mechanics govern ordering in a wide range of nanoparticles.

Nanoparticle clusters with Lennard-Jones geometries.

Noble gas and metal atoms form minimum-energy clusters. Here, we present analogous agglomerates of gold nanoparticles formed in oil-in-water emulsions. We exclude interfacial templating and nucleation-and-growth as formation mechanisms of these supraparticles. Similar to atomic clusters, the supraparticles form when a mobile precursor state can reconfigure until the nanoparticles' interactions with each other and with the liquid-liquid interface are maximized. This formation mechanism is in striking contrast to that previously reported for microparticle clusters.

Crystallization mechanisms in convective particle assembly.

Colloidal particles are continuously assembled into crystalline particle coatings using convective fluid flows. Assembly takes place inside a meniscus on a wetting reservoir. The shape of the meniscus defines the profile of the convective flow and the motion of the particles. We use optical interference microscopy, particle image velocimetry, and particle tracking to analyze the particles' trajectory from the liquid reservoir to the film growth front and inside the deposited film as a function of temperature. Our results indicate a transition from assembly at a static film growth front at high deposition temperatures to assembly in a precursor film with high particle mobility at low deposition temperatures. A simple model that compares the convective drag on the particles to the thermal agitation explains this behavior. Convective assembly mechanisms exhibit a pronounced temperature dependency and require a temperature that provides sufficient evaporation. Capillary mechanisms are nearly temperature independent and govern assembly at lower temperatures. The model fits the experimental data with temperature and particle size as variable parameters and allows prediction of the transition temperatures. While the two mechanisms are markedly different, dried particle films from both assembly regimes exhibit hexagonal particle packings. We show that films assembled by convective mechanisms exhibit greater regularity than those assembled by capillary mechanisms.