The attenuation of sedimentation and convection in microgravity can sometimes decrease irregularities formed during macromolecular crystal growth. Current terrestrial protein crystal growth (PCG) capabilities are very different than those used during the Shuttle era and that are currently on the International Space Station (ISS). The focus of this experiment was to demonstrate the use of a commercial off-the-shelf, high throughput, PCG method in microgravity. Using Protein BioSolutions' microfluidic Plug Maker™/CrystalCard™ system, we tested the ability to grow crystals of the regulator of glucose metabolism and adipogenesis: peroxisome proliferator-activated receptor gamma (apo-hPPAR-γ LBD), as well as several PCG standards. Overall, we sent 25 CrystalCards™ to the ISS, containing ~10,000 individual microgravity PCG experiments in a 3U NanoRacks NanoLab (1U = 10(3) cm.). After 70 days on the ISS, our samples were returned with 16 of 25 (64%) microgravity cards having crystals, compared to 12 of 25 (48%) of the ground controls. Encouragingly, there were more apo-hPPAR-γ LBD crystals in the microgravity PCG cards than the 1g controls. These positive results hope to introduce the use of the PCG standard of low sample volume and large experimental density to the microgravity environment and provide new opportunities for macromolecular samples that may crystallize poorly in standard laboratories.
Human dental enamel, the hardest tissue in the body, plays a vital role in protecting teeth from wear as a result of daily grinding and chewing as well as from chemical attack. It is well established that the mechanical strength and fatigue resistance of dental enamel are derived from its hierarchical structure, which consists of periodically arranged bundles of hydroxyapatite (HAP) nanowires. However, we do not yet have a full understanding of the in vivo HAP crystallization process that leads to this structure. Mg(2+) ions, which are present in many biological systems, regulate HAP crystallization by stabilizing its precursor, amorphous calcium phosphate (ACP), but their atomic-scale distribution within HAP is unknown. We use atom probe tomography to provide the first direct observations of an intergranular Mg-rich ACP phase between the HAP nanowires in mature human dental enamel. We also observe Mg-rich elongated precipitates and pockets of organic material among the HAP nanowires. These observations support the postclassical theory of amelogenesis (that is, enamel formation) and suggest that decay occurs via dissolution of the intergranular phase. This information is also useful for the development of more accurate models to describe the mechanical behavior of teeth.
Supereruptions catastrophically eject 100s-1000s of km3 of magma to the surface in a matter of days to a few months. In this study, we use zoning in quartz crystals from the Bishop Tuff (California) to assess the timescales over which a giant magma body transitions from relatively quiescent, pre-eruptive crystallization to rapid decompression and eruption. Quartz crystals in the Bishop Tuff have distinctive rims (<200 μm thick), which are Ti-rich and bright in cathodoluminescence (CL) images, and which can be used to calculate Ti diffusional relaxation times. We use synchrotron-based x-ray microfluorescence to obtain quantitative Ti maps and profiles along rim-interior contacts in quartz at resolutions of 1-5 μm in each linear dimension. We perform CL imaging on a scanning electron microscope (SEM) using a low-energy (5 kV) incident beam to characterize these contacts in high resolution (<1 μm in linear dimensions). Quartz growth times were determined using a 1D model for Ti diffusion, assuming initial step functions. Minimum quartz growth rates were calculated using these calculated growth times and measured rim thicknesses. Maximum rim growth times span from ~1 min to 35 years, with a median of ~4 days. More than 70% of rim growth times are less than 1 year, showing that quartz rims have mostly grown in the days to months prior to eruption. Minimum growth rates show distinct modes between 10-8 and 10-10 m/s (depending on sample), revealing very fast crystal growth rates (100s of nm to 10s of μm per day). Our data show that quartz rims grew well within a year of eruption, with most of the growth happening in the weeks or days preceding eruption. Growth took place under conditions of high supersaturation, suggesting that rim growth marks the onset of decompression and the transition from pre-eruptive to syn-eruptive conditions.
Crystalline materials are crucial to the function of living organisms, in the shells of molluscs, the matrix of bone, the teeth of sea urchins, and the exoskeletons of coccoliths. However, pathological biomineralization can be an undesirable crystallization process associated with human diseases. The crystal growth of biogenic, natural and synthetic materials may be regulated by the action of modifiers, most commonly inhibitors, which range from small ions and molecules to large macromolecules. Inhibitors adsorb on crystal surfaces and impede the addition of solute, thereby reducing the rate of growth. Complex inhibitor-crystal interactions in biomineralization are often not well elucidated. Here we show that two molecular inhibitors of calcium oxalate monohydrate crystallization-citrate and hydroxycitrate-exhibit a mechanism that differs from classical theory in that inhibitor adsorption on crystal surfaces induces dissolution of the crystal under specific conditions rather than a reduced rate of crystal growth. This phenomenon occurs even in supersaturated solutions where inhibitor concentration is three orders of magnitude less than that of the solute. The results of bulk crystallization, in situ atomic force microscopy, and density functional theory studies are qualitatively consistent with a hypothesis that inhibitor-crystal interactions impart localized strain to the crystal lattice and that oxalate and calcium ions are released into solution to alleviate this strain. Calcium oxalate monohydrate is the principal component of human kidney stones and citrate is an often-used therapy, but hydroxycitrate is not. For hydroxycitrate to function as a kidney stone treatment, it must be excreted in urine. We report that hydroxycitrate ingested by non-stone-forming humans at an often-recommended dose leads to substantial urinary excretion. In vitro assays using human urine reveal that the molecular modifier hydroxycitrate is as effective an inhibitor of nucleation of calcium oxalate monohydrate nucleation as is citrate. Our findings support exploration of the clinical potential of hydroxycitrate as an alternative treatment to citrate for kidney stones.
Material degradation due to precipitation of implanted helium (He) is a key concern in nuclear energy. Decades of research have mapped out the fate of He precipitates in metals, from nucleation and growth of equiaxed bubbles and voids to formation and bursting of surface blisters. By contrast, we show that He precipitates confined within nanoscale metal layers depart from their classical growth trajectories: They self-organize into elongated channels. These channels form via templated nucleation of He precipitates along layer surfaces followed by their growth and spontaneous coalescence into stable precipitate lines. The total line length and connectivity increases with the amount of implanted He, indicating that these channels ultimately interconnect into percolating “vascular” networks. Vascularized metal composites promise a transformative solution to He-induced damage by enabling in operando outgassing of He and other impurities while maintaining material integrity.
Many advanced technologies have relied on the availability of single crystals of appropriate material such as silicon for microelectronics or superalloys for turbine blades. Similarly, many promising materials could unleash their full potential if they were available in a single crystal form. However, the current methods are unsuitable for growing single crystals of these oftentimes incongruently melting, unstable or metastable materials. Here we demonstrate a strategy to overcome this hurdle by avoiding the gaseous or liquid phase, and directly converting glass into a single crystal. Specifically, Sb2S3 single crystals are grown in Sb-S-I glasses as an example of this approach. In this first unambiguous demonstration of an all-solid-state glass → crystal transformation, extraneous nucleation is avoided relative to crystal growth via spatially localized laser heating and inclusion of a suitable glass former in the composition. The ability to fabricate patterned single-crystal architecture on a glass surface is demonstrated, providing a new class of micro-structured substrate for low cost epitaxial growth, active planar devices, etc.
Control over the nucleation of new phases is highly desirable but elusive. Even though there is a long history of crystallization engineering by varying physicochemical parameters, controlling which polymorph crystallizes or whether a molecule crystallizes or forms an amorphous precipitate is still a poorly understood practice. Although there are now numerous examples of control using laser-induced nucleation, the absence of physical understanding is preventing progress. Here we show that the proximity of a liquid-liquid critical point or the corresponding binodal line can be used by a laser-tweezing potential to induce concentration gradients. A simple theoretical model shows that the stored electromagnetic energy of the laser beam produces a free-energy potential that forces phase separation or triggers the nucleation of a new phase. Experiments in a liquid mixture using a low-power laser diode confirm the effect. Phase separation and nucleation using a laser-tweezing potential explains the physics behind non-photochemical laser-induced nucleation and suggests new ways of manipulating matter.
In this paper, we present an investigation of the polymorphism of griseofulvin. In addition to the only reported crystalline form (form I), two new polymorphic forms (II and III) have been identified and characterized by differential scanning calorimetry and powder X-ray diffraction. Reasons why these two polymorphs were isolated during the present study, but not detected during the numerous previous studies on this drug, are also discussed. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
The most abundant polyphenol in green tea, epigallocatechin-3-gallate (EGCg), has recently received considerable attention due to the discovery of numerous health-promoting bioactivities. Despite reports of its poor oral bioavailability, EGCg has been included in many dietary supplement formulations. Conventional preformulation methods have been employed to improve the bioavailability of EGCg. However, these methods have limitations that hinder the development of EGCg as an effective therapeutic agent. In this study, we have utilized the basic concepts of crystal engineering and several crystallization techniques to screen for various solid crystalline forms of EGCg and evaluated the efficacy of crystal engineering for modulating the pharmacokinetics of EGCg. We synthesized and characterized seven previously undescribed crystal forms of EGCg including the pure crystal structure of EGCg. The aqueous solubility profiles of four new EGCg cocrystals were determined. These cocrystals were subsequently dosed at 100 mg EGCg per kg body weight in rats and the plasma levels were monitored over the course of eight hours following the single oral dose. Two of the EGCg cocrystals were found to exhibit modest improvements in relative bioavailability. Further, cocrystallization resulted in marked effects on pharmacokinetic parameters including CMAX, TMAX, area under curve, relative bioavailability, and apparent terminal half-life. Our findings suggest that modulation of the pharmacokinetic profile of EGCg is possible using cocrystallization and that it offers certain opportunities that could be useful during its development as a therapeutic agent.
A sustainable way to recover phosphorus (P) in swine wastewater involves a preliminary step of P dissolution followed by the separation of particulate organic matter. The next two steps are firstly the precipitation of struvite crystals done by adding a crystallization reagent (magnesia) and secondly the filtration of the crystals. A design of experiments with five process parameters was set up to optimize the size of the struvite crystals in a synthetic swine wastewater. More than 90% of P was recovered as large crystals of struvite in optimal conditions which were: low Mg:Ca ratio (2.25:1), the leading parameter, high N:P ratio (3:1), moderate stirring rate (between 45 and 90rpm) and low temperature (below 20°C).These results were obtained despite the presence of a large amount of calcium and using a cheap reactant (MgO). The composition of the precipitates was identified by Raman analysis and solid dissolution. Results showed that amorphous calcium phosphate (ACP) co-precipitated with struvite and that carbonates were incorporated with solid fractions.