Nano-microcrystals revealed on Tang dynasty gilded bronze using advanced TEM-SEM and synchrotron methods.

Over the years, numerous gold and silver artifacts have been excavated from the tombs of the Tang dynasty, which give evidence of the sophisticated metalworking techniques at that time. Few of the artifacts were thoroughly studied and their manufacturing processes were barely known. The present investigation concerns a metal headgear from a newly excavated tomb of a female in Xi'an of the Tang dynasty (618-907 A.D.), using advanced techniques in a complementary way, especially performing a detailed analysis of the corrosion products and alloying processes. The combined state-of-the-art methods and instrumentation used for the corrosion study included spectroscopy, diffraction, electron microscopy, synchrotron and their versions for specific measurements and sample preparation. The investigated headgear metal consists of a copper-based core, which is gilded by a thin gold layer, consisting of an Au-Hg alloy with a thin layer of about 400 nm. The technique used for shaping and hammered embellishments led to the creation of nanosized grains on the side that would eventually be the interior of the headgear. It was gilded using the mercury-amalgamation process, and the liquid diffusion caused the development of intermetallic compounds. This is the first recorded instance of these nano-scale and eutectic phases being observed on objects from an archaeological context. The crystallographic analysis offered valuable insights into the formation of needle-like malachite crystals growing on a layer of cuprite found on the surface of the corroded piece. The results highlight that the artisans utilized advanced methods in the creation of funerary items during the Tang dynasty.

Quantitative 3D structural analysis of small colloidal assemblies under native conditions by liquid-cell fast electron tomography.

Electron tomography has become a commonly used tool to investigate the three-dimensional (3D) structure of nanomaterials, including colloidal nanoparticle assemblies. However, electron microscopy is typically done under high-vacuum conditions, requiring sample preparation for assemblies obtained by wet colloid chemistry methods. This involves solvent evaporation and deposition on a solid support, which consistently alters the nanoparticle organization. Here, we suggest using electron tomography to study nanoparticle assemblies in their original colloidal liquid environment. To address the challenges related to electron tomography in liquid, we devise a method that combines fast data acquisition in a commercial liquid-cell with a dedicated alignment and reconstruction workflow. We present the advantages of this methodology in accurately characterizing two different systems. 3D reconstructions of assemblies comprising polystyrene-capped Au nanoparticles encapsulated in polymeric shells reveal less compact and more distorted configurations for experiments performed in a liquid medium compared to their dried counterparts. A similar expansion can be observed in quantitative analysis of the surface-to-surface distances of self-assembled Au nanorods in water rather than in a vacuum, in agreement with bulk measurements. This study, therefore, emphasizes the importance of developing high-resolution characterization tools that preserve the native environment of colloidal nanostructures.

Simple ePDF: A Pair Distribution Function Method Based on Electron Diffraction Patterns to Reveal the Local Structure of Amorphous and Nanocrystalline Materials.

Amorphous, glassy or disordered materials play important roles in developing structural materials from metals or ceramics, devices from semiconductors or medicines from organic compounds. Their local structure is frequently similar to crystalline ones. A computer program is presented here that runs under the Windows operating system on a PC to extract pair distribution function (PDF) from electron diffraction in a transmission electron microscope (TEM). A polynomial correction reduces small systematic deviations from the expected average Q-dependence of scattering. Neighbor distance and coordination number measurements are supplemented by either measurement or enforcement of number density. Quantification of similarity is supported by calculation of Pearson's correlation coefficient and fingerprinting. A rough estimate of fractions in a mixture is computed by multiple least-square fitting using the PDFs from components of the mixture. PDF is also simulated from crystalline structural models (in addition to measured ones) to be used in libraries for fingerprinting or fraction estimation. Crystalline structure models for simulations are obtained from CIF files or str files of ProcessDiffraction. Data from inorganic samples exemplify usage. In contrast to previous free ePDF programs, our stand-alone program does not need a special software environment, which is a novelty. The program is available from the author upon request.

High-Resolution Electron Diffraction of Hydrated Protein Crystals at Room Temperature.

Structural characterization is crucial to understanding protein function. Compared with X-ray diffraction methods, electron crystallography can be performed on nanometer-sized crystals and can provide additional information from the resulting Coulomb potential map. Whereas electron crystallography has successfully resolved three-dimensional structures of vitrified protein crystals, its widespread use as a structural biology tool has been limited. One main reason is the fragility of such crystals. Protein crystals can be easily damaged by mechanical stress, change in temperature, or buffer conditions as well as by electron irradiation. This work demonstrates a methodology to preserve these nanocrystals in their natural environment at room temperature for electron diffraction experiments as an alternative to existing cryogenic techniques. Lysozyme crystals in their crystallization solution are hermetically sealed via graphene-coated grids, and their radiation damage is minimized by employing a low-dose data collection strategy in combination with a hybrid-pixel direct electron detector. Diffraction patterns with reflections of up to 3 Å are obtained and successfully indexed using a template-matching algorithm. These results demonstrate the feasibility of in situ protein electron diffraction. The method described will also be applicable to structural studies of hydrated nanocrystals important in many research and technological developments.

In vitro Evaluation of Paliperidone Palmitate Loaded Cubosomes Effective for Nasal-to-Brain Delivery.

Introduction: This work aimed to develop chitosan-coated cubosomal nanoparticles intended for nose-to-brain delivery of paliperidone palmitate. They were compared with standard and cationic cubosomal nanoparticles. This comparison relies on numerous classical in vitro tests and powder deposition within a 3D-printed nasal cast. Methods: Cubosomal nanoparticles were prepared by a Bottom-up method followed by a spray drying process. We evaluated their particle size, polydispersity index, zeta-potential, encapsulation efficiency, drug loading, mucoaffinity properties and morphology. The RPMI 2650 cell line was used to assess the cytotoxicity and cellular permeation. An in vitro deposition test within a nasal cast completed these measurements. Results: The selected chitosan-coated cubosomal nanoparticles loaded with paliperidone palmitate had a size of 305.7 ± 22.54 nm, their polydispersity index was 0.166 ± 0.022 and their zeta potential was +42.4 ± 0.2 mV. This formulation had a drug loading of 70% and an encapsulation efficiency of 99.7 ± 0.1%. Its affinity with mucins was characterized by a ΔZP of 20.93 ± 0.31. Its apparent permeability coefficient thought the RPMI 2650 cell line was 3.00E-05 ± 0.24E-05 cm/s. After instillation in a 3D-printed nasal cast, the fraction of the injected powder deposited in the olfactory region reached 51.47 ± 9.30% in the right nostril and 41.20 ± 4.59% in the left nostril, respectively. Conclusion: The chitosan coated cubosomal formulation seems to be the most promising formulation for nose-to-brain delivery. Indeed, it has a high mucoaffinity and a significantly higher apparent permeability coefficient than the two other formulations. Finally, it reaches well the olfactory region.

Reliable Characterization of Organic & Pharmaceutical Compounds with High Resolution Monochromated EEL Spectroscopy.

Organic and biological compounds (especially those related to the pharmaceutical industry) have always been of great interest for researchers due to their importance for the development of new drugs to diagnose, cure, treat or prevent disease. As many new API (active pharmaceutical ingredients) and their polymorphs are in nanocrystalline or in amorphous form blended with amorphous polymeric matrix (known as amorphous solid dispersion-ASD), their structural identification and characterization at nm scale with conventional X-Ray/Raman/IR techniques becomes difficult. During any API synthesis/production or in the formulated drug product, impurities must be identified and characterized. Electron energy loss spectroscopy (EELS) at high energy resolution by transmission electron microscope (TEM) is expected to be a promising technique to screen and identify the different (organic) compounds used in a typical pharmaceutical or biological system and to detect any impurities present, if any, during the synthesis or formulation process. In this work, we propose the use of monochromated TEM-EELS, to analyze selected peptides and organic compounds and their polymorphs. In order to validate EELS for fingerprinting (in low loss/optical region) and by further correlation with advanced DFT, simulations were utilized.

Effect of Internal Pressure and Temperature on Phase Transitions in Perovskite Oxides: The Case of the Solid Oxide Fuel Cell Cathode Materials of the La2-xSrxCoTiO6 Series.

The symmetry of the room-temperature (RT) structure of title compounds La2-xSrxCoTiO6-δ changes with x, from P21/n (0 ≤ x ≤ 0.2) to Pnma (0.3 ≤ x ≤ 0.5) and to R3̅c (0.6 ≤ x ≤ 1). For x = 1 the three pseudocubic cell parameters become very close suggesting a transition to a cubic structure for higher Sr contents. Similar phase transitions were expected to occur on heating, paralleling the effect of internal pressure induced by substitution of La3+ by Sr2+. However, only some of these aforementioned transitions have been thermally induced. The symmetry-adapted modes formalism is used in the structural refinements and fitting of neutron diffraction data recorded from RT to 1273 K. Thus, for x = 1, the out-of-phase tilting of the BO6 octahedra vanishes progressively on heating, and a cubic structure with Pm3̅m symmetry is found at 1073 K. For lower Sr contents this transition is predicted to occur far above the temperature limit of common experimental setups. The analysis of the evolution of the perovskite tolerance factor, t-factor, with both Sr content and temperature indicates that temperature has a limited ability to release structural stress and thus to enable transitions to more symmetric phases. This is particularly true when compared to the effect of internal pressure induced by substitution of La by Sr. The existence of phase transitions in materials for solid oxide fuel cells that are usually exposed to heating-cooling cycles may have a detrimental effect. This work suggests strategies to stabilize the high-symmetry high-temperature phase of perovskite oxides through internal-pressure chemically induced.