Effects of Structural Relaxation of Glass-Forming Melts on the Overall Crystallization Kinetics in Cooling and Heating.

In the theoretical treatment of crystallization, it is commonly assumed that the relaxation processes of a liquid proceed quickly as compared to crystal nucleation and growth processes. Actually, it is supposed that a liquid is always located in the metastable state corresponding to the current values of pressure and temperature. However, near and below the glass transition temperature, Tg, this condition is commonly not fulfilled. In such cases, in the treatment of crystallization, deviations in the state of the liquid from the respective metastable equilibrium state have to be accounted for when determining the kinetic coefficients governing the crystallization kinetics, the thermodynamic driving force of crystallization, and the surface tension of the aggregates of the newly evolving crystal phase including the surface tension of critical clusters considerably affecting the crystal nucleation rate. These factors may greatly influence the course of the overall crystallization process. A theoretical analysis of the resulting effects is given in the present paper by numerical solutions of the J(ohnson)-M(ehl)-A(vrami)-K(olmogorov) equation employed as the tool to model the overall crystallization kinetics and by analytical estimates of the crystallization peak temperatures in terms of the dependence on cooling and heating rates. The results are shown to be in good agreement with the experimental data. Possible extensions of the theory are anticipated and will be explored in future analysis.

Kinetic Stability and Glass-Forming Ability of Thermally Labile Quinolone Antibiotics.

The application of drugs in the amorphous state is one way to improve their bioavailability. As such, the determination of the optimal conditions for production and the assessment of the stability of the amorphous system are actively researched topics of present-day pharmaceutical science. In the present work, we have studied the kinetic stability and glass-forming ability of the thermally labile quinolone antibiotics using fast scanning calorimetry. The critical cooling rates for avoiding crystallization of the melts of oxolinic and pipemidic acids and sparfloxacin were determined to be 10 000, 40, and 80 K·s-1, respectively. The studied antibiotics were found to be "strong" glass formers. Based on a combination of nonisothermal and isothermal kinetic approaches, the Nakamura model was suitable for describing the crystallization process of the amorphous forms of the quinolone antibiotics.

Determination of Cooperativity Length in a Glass-Forming Polymer.

To describe the properties of glass-forming liquids, the concepts of a cooperativity length or the size of cooperatively rearranging regions are widely employed. Their knowledge is of outstanding importance for the understanding of both thermodynamic and kinetic properties of the systems under consideration and the mechanisms of crystallization processes. By this reason, methods of experimental determination of this quantity are of outstanding importance. Proceeding in this direction, we determine the so-called cooperativity number and, based on it, the cooperativity length by experimental measurements utilizing AC calorimetry and quasi-elastic neutron scattering (QENS) at comparable times. The results obtained are different in dependence on whether temperature fluctuations in the considered nanoscale subsystems are either accounted for or neglected in the theoretical treatment. It is still an open question, which of these mutually exclusive approaches is the correct one. As shown in the present paper on the example of poly(ethyl methacrylate) (PEMA), the cooperative length of about 1 nm at 400 K and a characteristic time of ca. 2 µs determined from QENS coincide most consistently with the cooperativity length determined from AC calorimetry measurements if the effect of temperature fluctuations is incorporated in the description. This conclusion indicates that-accounting for temperature fluctuations-the characteristic length can be derived by thermodynamic considerations from the specific parameters of the liquid at the glass transition and that temperature does fluctuate in small subsystems.

Some aspects of the glass transition of polyvinylpyrrolidone depending on the molecular mass.

Amorphous polymers currently have a wide range of applications, including the production of amorphous solid dispersions in the pharmaceutical industry. This application requires knowledge of the kinetic parameters of the glass transition process, which are the key to the formation of the end product. In the present work, we have thoroughly investigated the glass transition in the biocompatible polymer polyvinylpyrrolidone as a function of the polymer molecular mass, using differential scanning calorimetry, fast scanning calorimetry, and broadband dielectric spectroscopy. We have determined the dependence of the difference between the isobaric specific heat capacities of the liquid and the glass on the dynamic glass transition temperature, volume, and number of particles included in the cooperatively rearranging regions. A linear dependence between the shift factor from the Frenkel-Kobeko-Reiner equation and the molecular mass of polyvinylpyrrolidone was established. The results of the present work help in choosing the optimal excipient for the development of solid dispersions based on amorphous polymers.

Radial growth rate of near-critical crystal nuclei in poly(l-lactic acid) (PLLA) in Tammann's two-stage development method.

The specific features of crystal nucleation widely determine the morphology of the evolving crystalline material. Crystal nucleation is, as a rule, not accessible by direct observation of the nuclei, which develop with time. This limitation is caused by the small size (nanometer scale) of the critical nuclei and the stochastic nature of their formation. We describe an experimental approach to the determination of specific features of the cluster size distribution employing fast scanning calorimetry at scanning rates up to 10 000 K s-1. The surviving cluster fraction is determined by selectively melting/dissolving clusters smaller than the critical size corresponding to the highest temperature of a short spike positioned between the nucleation and the development stage in Tammann's two-stage method. This approach allows for estimating the time evolution of the radius of the largest detectable clusters in the distribution. Knowing this radius as a function of nucleation time allows for determining a radial growth rate. In the example of poly(l-lactic acid) (PLLA), the order of magnitude estimate of radial growth rates of clusters of about 2-5 nm yields values between 10-5 and 10-3 nm s-1. The radial growth rate of micrometer-sized spherulites is available from optical microscopy. The corresponding values are about three orders of magnitude higher than the values for the nanometer-sized clusters. This difference is explainable by stochastic effects, transient features, and the size dependence of the growth processes on the nanometer scale. The experimental and (order of magnitude) classical nucleation theory estimates agree well.

Hyperhidrosis: A Central Nervous Dysfunction of Sweat Secretion.

Hyperhidrosis (HH) is a central nervous dysfunction characterized by abnormally increased sweating due to a central dysregulation of sweat secretion. HH significantly affects the quality of life of patients in their private, social and professional environments. Physiologically, sweating is a mechanism that regulates body temperature, but it may also be triggered by emotional or gustatory stimuli. There are two main types of sweat glands: eccrine and apocrine glands. The central nervous system controls sweat secretion through the release of neurotransmitters into the autonomous nervous system (ANS) that activate the sweat glands. The hypothalamus has two separate neuronal pathways, one for thermoregulation and one for emotions. HH may thus be due to either a neuronal dysfunction of ANS regulation leading to a hyperactivity of the sympathetic nervous system, or to abnormal central processing of emotions. Crucially, there is no dysfunction of the sweat glands themselves. Various pathogenic mechanisms have been proposed to be involved in pathological sweat secretion in HH, ranging from structural changes within the ANS to increased expression of aquaporin 5 and upregulation of activin A receptor type 1 in eccrine sweat glands. Although a genetic predisposition has been demonstrated, it remains unclear exactly which genes are involved. To identify new, potential therapeutic targets and to improve treatment options, a good understanding of the signaling pathways involved, the underlying mechanisms, and the genetic components is essential. In this review we discuss the various aspects of sweat physiology and function that are necessary to explain pathological sweating. Our aim is to raise awareness of the complexity of HH to promote a better understanding of the disorder.

Bulk Enthalpy of Melting of Poly (l-lactic acid) (PLLA) Determined by Fast Scanning Chip Calorimetry.

The bulk enthalpy of melting of α-crystals of poly (L-lactic acid) (PLLA) is evaluated by fast scanning calorimetry (FSC), by correlating the melting enthalpy of samples of different crystallinity with the corresponding heat capacity at 90 °C, that is at a temperature higher than the glass transition temperature of the bulk amorphous phase and lower than the melting temperature. Extrapolation of this relationship for crystals formed at 140 °C towards the heat capacity of fully solid PLLA yields a value of 104.5±6 J g-1 when melting occurs at 180-200 °C. The analysis relies on a two-phase structure, that is, absence of a vitrified rigid amorphous fraction (RAF) at the temperature of analysis the solid fraction (90 °C). Formation and vitrification of an RAF are suppressed by avoiding continuation of primary crystallization and secondary crystallization during cooling the system from the crystallization temperature of 140 °C to 90 °C, making use of the high cooling capacity of FSC. Small-angle X-ray scattering (SAXS) confirmed thickening of initially grown lamellae which only is possible if these lamellae are not surrounded by a glassy RAF. Linear crystallinity values obtained by SAXS and calorimetrically determined enthalpy-based crystallinities agree close to each other.

Refolding of Lysozyme in Glycerol as Studied by Fast Scanning Calorimetry.

The folding of lysozyme in glycerol was monitored by the fast scanning calorimetry technique. Application of a temperature-time profile with an isothermal segment for refolding allowed assessment of the state of the non-equilibrium protein ensemble and gave information on the kinetics of folding. We found that the non-equilibrium protein ensemble mainly contains a mixture of unfolded and folded protein forms and partially folded intermediates, and enthalpic barriers control the kinetics of the process. Lysozyme folding in glycerol follows the same or similar triangular mechanism described in the literature for folding in water. The unfolding enthalpy of the intermediate must be no lower than 70% of the folded form, while the activation barrier for the unfolding of the intermediate (ca. 140 kJ/mol) is about 100 kJ/mol lower than that of the folded form (ca. 240-260 kJ/mol).

Crystal Nucleation and Growth in Cross-Linked Poly(ε-caprolactone) (PCL).

The crystal nucleation and overall crystallization kinetics of cross-linked poly(ε-caprolactone) was studied experimentally by fast scanning calorimetry in a wide temperature range. With an increasing degree of cross-linking, both the nucleation and crystallization half-times increase. Concurrently, the glass transition range shifts to higher temperatures. In contrast, the temperatures of the maximum nucleation and the overall crystallization rates remain the same, independent of the degree of cross-linking. The cold crystallization peak temperature generally increases as a function of heating rate, reaching an asymptotic value near the temperature of the maximum growth rate. A theoretical interpretation of these results is given in terms of classical nucleation theory. In addition, it is shown that the average distance between the nearest cross-links is smaller than the estimated lamellae thickness, which indicates the inclusion of cross-links in the crystalline phase of the polymer.

Surface Crystal Nucleation and Growth in Poly (ε-caprolactone): Atomic Force Microscopy Combined with Fast Scanning Chip Calorimetry.

By using an atomic force microscope (AFM) coupled to a fast scanning chip calorimeter (FSC), AFM-tip induced crystal nucleation/crystallization in poly (ε-caprolactone) (PCL) has been studied at low melt-supercooling, that is, at a temperature typically not assessable for melt-crystallization studies. Nanogram-sized PCL was placed on the active/heatable area of the FSC chip, melted, and then rapidly cooled to 330 K, which is 13 K below the equilibrium melting temperature. Subsequent isothermal crystallization at this temperature was initiated by a soft-tapping AFM-tip nucleation event. Crystallization starting at such surface nucleus led to formation of a single spherulite within the FSC sample, as concluded from the radial symmetry of the observed morphology. The observed growth rate in the sub-micron thin FSC sample, nucleated at its surface, was found being much higher than in the case of bulk crystallization, emphasizing a different growth mechanism. Moreover, distinct banding/ring-like structures are observed, with the band period being less than 1 µm. After crystallization, the sample was melted for gaining information about the achieved crystallinity and the temperature range of melting, both being similar compared to much slower bulk crystallization at the same temperature but for a much longer time.

Nucleation Behavior of a Single Al-20Si Particle Rapidly Solidified in a Fast Scanning Calorimeter.

Understanding the rapid solidification behavior characteristics, nucleation undercooling, and nucleation mechanism is important for modifying the microstructures and properties of metal alloys. In order to investigate the rapid solidification behavior in-situ, accurate measurements of nucleation undercooling and cooling rate are required in most rapid solidification processes, e.g., in additive manufacturing (AM). In this study, differential fast scanning calorimetry (DFSC) was applied to investigate the nucleation kinetics in a single micro-sized Al-20Si (mass%) particle under a controlled cooling rate of 5000 K/s. The nucleation rates of primary Si and secondary α-Al phases were calculated by a statistical analysis of 300 identical melting/solidification experiments. Applying a model based on the classical nucleation theory (CNT) together with available thermodynamic data, two different heterogeneous nucleation mechanisms of primary Si and secondary α-Al were proposed, i.e., surface heterogeneous nucleation for primary Si and interface heterogenous nucleation for secondary α-Al. The present study introduces a practical method for a detailed investigation of rapid solidification behavior of metal particles to distinguish surface and interface nucleation.

Spatial inhomogeneity, interfaces and complex vitrification kinetics in a network forming nanocomposite.

A detailed calorimetric study on an epoxy-based nanocomposite system was performed employing bisphenol A diglycidyl ether (DGEBA) cured with diethylenetriamine (DETA) as the polymer matrix and a taurine-modified MgAL layered double hydroxide (T-LDH) as the nanofiller. The -NH2 group of taurine can react with DGEBA improving the interaction of the polymer with the filler. The combined X-ray scattering and electron microscopy data showed that the nanocomposite has a partially exfoliated morphology. Calorimetric studies were performed using conventional DSC, temperature modulated DSC (TMDSC) and fast scanning calorimetry (FSC) in the temperature modulated approach (TMFSC) to investigate the vitrification and molecular mobility dependent on the filler concentration. First, TMDSC and NMR were used to estimate the amount of the rigid amorphous fraction which consists of immobilized polymer segments at the nanoparticle surface. It was found to be 40 wt% for the highest filler concentration, indicating that the interface dominates the overall macroscopic properties and behavior of the material to a great extent. Second, the relaxation rates of the α-relaxation obtained by TMDSC and TMFSC were compared with the thermal and dielectric relaxation rates measured by static FSC. The investigation revealed that the system shows two distinct α-relaxation processes. Furthermore, two separate vitrification mechanisms were also found for a bulk network-former without geometrical confinement as also confirmed by NMR. This was discussed in terms of the intrinsic spatial heterogeneity on a molecular scale, which becomes more pronounced with increasing nanofiller content.

Thermal Stability and Nucleation Efficacy of Shear-Induced Pointlike and Shishlike Crystallization Precursors.

The different thermal stabilities of shear-induced pointlike and shishlike crystallization precursors of polyamide 11, generated in a parallel-plate rheometer and coexisting in the same sample, were quantified by hot-stage microscopy, by performing self-seed crystallization experiments. Crystals formed at low supercooling of the melt from these different types of precursors melt at about the same temperature. Annealing of the melt at different temperatures for a predefined time revealed dissolution/disordering of these precursors at 10-15 K higher temperature, near the equilibrium melting point. Despite their similar thermal stabilities, pointlike and shishlike crystallization precursors exhibit distinctly different nucleation efficacies. Under identical crystallization conditions, shishlike precursors cause faster crystallization than pointlike crystal nuclei. The faster crystallization of the shishlike nuclei can be explained, for example, by (a) the larger size of the shishlike precursors, providing numerous nucleation sites; (b) the more perfect chain conformation at the shish surface, which serves as a substrate for crystallization; or perhaps (c) the higher local orientation of the surrounding melt compared with molecular segments near pointlike nuclei, reducing the activation energy for crystallization.

Genome-wide linkage analysis of families with primary hyperhidrosis.

Primary focal hyperhidrosis (PFH, OMIM %144110) is a genetically influenced condition characterised by excessive sweating. Prevalence varies between 1.0-6.1% in the general population, dependent on ethnicity. The aetiology of PFH remains unclear but an autosomal dominant mode of inheritance, incomplete penetrance and variable phenotypes have been reported. In our study, nine pedigrees (50 affected, 53 non-affected individuals) were included. Clinical characterisation was performed at the German Hyperhidrosis Centre, Munich, by using physiological and psychological questionnaires. Genome-wide parametric linkage analysis with GeneHunter was performed based on the Illumina genome-wide SNP arrays. Haplotypes were constructed using easyLINKAGE and visualised via HaploPainter. Whole-exome sequencing (WES) with 100x coverage in 31 selected members (24 affected, 7 non-affected) from our pedigrees was achieved by next generation sequencing. We identified four genome-wide significant loci, 1q41-1q42.3, 2p14-2p13.3, 2q21.2-2q23.3 and 15q26.3-15q26.3 for PFH. Three pedigrees map to a shared locus at 2q21.2-2q23.3, with a genome-wide significant LOD score of 3.45. The chromosomal region identified here overlaps with a locus at chromosome 2q22.1-2q31.1 reported previously. Three families support 1q41-1q42.3 (LOD = 3.69), two families share a region identical by descent at 2p14-2p13.3 (LOD = 3.15) and another two families at 15q26.3 (LOD = 3.01). Thus, our results point to considerable genetic heterogeneity. WES did not reveal any causative variants, suggesting that variants or mutations located outside the coding regions might be involved in the molecular pathogenesis of PFH. We suggest a strategy based on whole-genome or targeted next generation sequencing to identify causative genes or variants for PFH.

Stability of Crystal Nuclei of Poly (butylene isophthalate) Formed Near the Glass Transition Temperature.

Tammann's two-stage crystal-nuclei-development method is applied for analysis of the thermal stability of homogenously formed crystal nuclei of poly(butylene isophthalate) (PBI) as well as their possible reorganization on transferring them to the growth temperature, using fast scanning chip calorimetry. Crystal nuclei were formed at 50 °C, that is, at a temperature only slightly higher than the glass transition temperature, and developed to crystals within a pre-defined time at the growth temperature of 85 °C. The number of nuclei, overcritical at the growth temperature, was detected as a function of the transfer-conditions (maximum temperature, heating rate) by evaluation of the developed crystal fraction. For different size-distributions of crystal nuclei, as controlled by the nucleation time, there is detected distinct reduction of the nuclei number on heating to maximum temperatures higher than about 90 to 110 °C, with the latter value holding for longer nucleation time. Longer nucleation allows for both increasing the absolute nuclei number and generation of an increased fraction of larger nuclei. Heating at 1000 K/s to 140-150 °C causes "melting" of even the most stable nuclei. While direct transfer of crystal nuclei from the nucleation temperature (50 °C) to the growth temperature (85 °C) reveals negligible effect of the transfer-heating rate, in-between heating to higher temperatures is connected with distinct nuclei-reorganization above 85 °C on heating slower than 1000-10.000 K/s. The performed study not only provides specific valuable information about the thermal characteristics of crystal nuclei of PBI but also highlights the importance of proper design of Tammann's nuclei development experiment for analysis of nuclei numbers. With the evaluation of critical rates of temperature-change for suppression of non-isothermal formation of both nuclei and crystals, the kinetics of crystallization of the slow crystallizing PBI is further quantified.

Melting properties of amino acids and their solubility in water.

The state-of-the-art unit operation for separation and purification of amino acids is still crystallization, which requires solubility data and melting properties of pure compounds. Since measuring solubility is time-consuming, prediction tools are desired. Further, melting properties are not yet available due to decomposition of amino acids upon slow heating. In this work, melting properties of twenty amino acids (except Met) were measured by Fast Scanning Calorimetry (FSC) with heating rates up to 20 000 K s-1. PC-SAFT was used to predict interactions in amino acid + water systems. Additionally, solubility, pH, and PXRD was measured. By combining FSC and PC-SAFT, the solubility of 15 amino acids was successfully predicted in a wide temperature range in good agreement with the experimental data. Thus, this work provides melting properties of amino acids for the first time and highlights the usefulness of such data to predict material properties such as aqueous solubility of amino acids.

Review of the Quench Sensitivity of Aluminium Alloys: Analysis of the Kinetics and Nature of Quench-Induced Precipitation.

For aluminium alloys, precipitation strengthening is controlled by age-hardening heat treatments, including solution treatment, quenching, and ageing. In terms of technological applications, quenching is considered a critical step, because detrimental quench-induced precipitation must be avoided to exploit the full age-hardening potential of the alloy. The alloy therefore needs to be quenched faster than a critical cooling rate, but slow enough to avoid undesired distortion and residual stresses. These contrary requirements for quenching can only be aligned based on detailed knowledge of the kinetics of quench-induced precipitation. Until the beginning of the 21st century, the kinetics of relevant solid-solid phase transformations in aluminium alloys could only be estimated by ex-situ testing of different properties. Over the past ten years, significant progress has been achieved in this field of materials science, enabled by the development of highly sensitive differential scanning calorimetry (DSC) techniques. This review presents a comprehensive report on the solid-solid phase transformation kinetics in Al alloys covering precipitation and dissolution reactions during heating from different initial states, dissolution during solution annealing and to a vast extent quench-induced precipitation during continuous cooling over a dynamic cooling rate range of ten orders of magnitude. The kinetic analyses are complemented by sophisticated micro- and nano-structural analyses and continuous cooling precipitation (CCP) diagrams are derived. The measurement of enthalpies released by quench-induced precipitation as a function of the cooling rate also enables predictions of the quench sensitivities of Al alloys using physically-based models. Various alloys are compared, and general aspects of quench-induced precipitation in Al alloys are derived.

Nanoscale Heat Conduction in CNT-POLYMER Nanocomposites at Fast Thermal Perturbations.

Nanometer scale heat conduction in a polymer/carbon nanotube (CNT) composite under fast thermal perturbations is described by linear integrodifferential equations with dynamic heat capacity. The heat transfer problem for local fast thermal perturbations around CNT is considered. An analytical solution for the nonequilibrium thermal response of the polymer matrix around CNT under local pulse heating is obtained. The dynamics of the temperature distribution around CNT depends significantly on the CNT parameters and the thermal contact conductance of the polymer/CNT interface. The effect of dynamic heat capacity on the local overheating of the polymer matrix around CNT is considered. This local overheating can be enhanced by very fast (about 1 ns) components of the dynamic heat capacity of the polymer matrix. The results can be used to analyze the heat transfer process at the early stages of "shish-kebab" crystal structure formation in CNT/polymer composites.

Visualization of Polymer Crystallization by In Situ Combination of Atomic Force Microscopy and Fast Scanning Calorimetry.

A chip-based fast scanning calorimeter (FSC) is used as a fast hot-stage in an atomic force microscope (AFM). This way, the morphology of materials with a resolution from micrometers to nanometers after fast thermal treatments becomes accessible. An FSC can treat the sample isothermally or at heating and cooling rates up to 1 MK/s. The short response time of the FSC in the order of milliseconds enables rapid changes from scanning to isothermal modes and vice versa. Additionally, FSC provides crystallization/melting curves of the sample just imaged by AFM. We describe a combined AFM-FSC device, where the AFM sample holder is replaced by the FSC chip-sensor. The sample can be repeatedly annealed at pre-defined temperatures and times and the AFM images can be taken from exactly the same spot of the sample. The AFM-FSC combination is used for the investigation of crystallization of polyamide 66 (PA 66), poly(ether ether ketone) (PEEK), poly(butylene terephthalate) (PBT) and poly(ε-caprolactone) (PCL).