Crystal Nucleation Rate Research Articles

Emerging microfluidic platforms for crystallization process development

The microfluidic platform offers an exclusive environment compatible with different analytical tools to investigate crystallization processes. Moreover, microfluidic devices allow precise and convenient control of crystallization conditions at nano or meso scales, making them suitable for pharmaceutical and energy applications. These miniaturized screening devices can be effective during drug discovery stages for screening active ingredients available on micro/milligram scales. In this review, we discuss the advancements and applications of microfluidics platforms in the development of crystallization processes, including measurement of crystal growth and nucleation rates, screening of co-crystals, polymorphs and morphology, synthesis of nanocrystals, and determination of metastable zones and solubility. In addition, the latest microfluidics setups for high-throughput screening and lab-on-chip enhancements with sensors and automation are presented in this review. Lastly, an outlook on how microfluidic platforms can be adapted to improve workflow in crystallization process development is presented.

Effects of L-Arginine and L-Aspartic Acid on the Nucleation and Growth Rates of Calcium Oxalate Crystals.

Effects of L-Arginine and L-Aspartic Acid on the Nucleation and Growth Rates of Calcium Oxalate Crystals.

Role of Kinetics and Thermodynamics in Controlling the Crystal Structure of Nickel Nanoparticles Formed on Reduced Graphene Oxide: Implications for Energy Storage and Conversion Applications

Ultrafast heating has emerged recently to speed up the synthesis processes of nanoparticles and control their morphology. However, it is not clear how the heating rate affects the formation of metal nanoparticles, particularly those formed on substrates. Here, we explored the formation of nickel (Ni) nanoparticles on graphene oxide (GO) substrates under slow (20 °C/min) and ultrafast (103 °C/s) heating rates. The experiments were performed in situ on heating microchip devices using an aberration-corrected transmission electron microscope. Interestingly, the GO structure was the most effective in controlling the stability of nanoparticles when ultrafast heating was employed, leading to a hexagonally close-packed Ni phase (hcp-Ni) because of less lattice mismatch with the graphitic substrate. On the contrary, fcc-Ni nanoparticles formed under a slow heating process where no strong correlation with the GO crystal structure was observed. Additionally, ultrafast heating resulted in smaller-size nanoparticles which could be ascribed to rapid reduction, nucleation rate, and higher diffusion barrier of hcp-Ni crystals on rGO. Nevertheless, the stability of the crystal structure of the nickel nanoparticles remains unaffected by their size. These results indicate the crucial role of the substrate on crystal structure during the nonequilibrium processing of materials and the competing effects of thermodynamics versus kinetics in creating novel phases of materials for energy storage and conversion applications.

Micro-thermography for imaging ice crystal growth and nucleation inside non-transparent materials

Ice crystal growth and nucleation rate measurements are usually done using light microscopy in liquid and transparent samples. Yet, the understanding of important practical problems depends on monitoring ice growth inside solid materials, for example how rapid ice growth leads to structural damage of food, or how the final structure of cementitious materials is affected by ice during curing. Imaging crystal growth inside solid materials cannot be done with visible light and is intrinsically more challenging than visible light imaging. Thermography is a technique that uses thermal (infrared) cameras to monitor temperature changes in a material, and it has been used to provide a qualitative description of ice propagation with a low spatial resolution. Here, we describe a method that uses a novel micro-thermography system to image ice nucleation and growth inside non-transparent samples. This method relies on two major components: a cold stage with accurate temperature control (±0.001 °C) and a thermal camera with high spatial and temperature resolution. Our experiments include imaging of ice formation and growth in pure water first and then inside plant leaves used as a model for a non-transparent material. An ice growth rate of 2.2 mm/s was measured inside a plant leaf at -12 °C, and ice nucleation in single plant cells was observed as a hotspot having a diameter of 160 µm. The results presented here provide an experimental proof that high-quality imaging of ice growth is achievable, thus paving the way for quantitative measurements of ice growth kinetics and ice nucleation in solid materials.

Zinc Stable Isotope Fractionation Mechanisms during Adsorption on and Substitution in Iron (Hydr)oxides.

The Zn isotope fingerprint is widely used as a proxy of various environmental geochemical processes, so it is crucial to determine which are the mechanisms responsible for isotopic fractionation. Iron (Fe) (hydr)oxides greatly control the cycling and fate and thus isotope fractionation factors of Zn in terrestrial environments. Here, Zn isotope fractionation and related mechanisms during adsorption on and substitution in three FeOOH polymorphs are explored. Results demonstrate that heavy Zn isotopes are preferentially enriched onto solids, with almost similar isotopic offsets (Δ66/64Znsolid-solution = 0.25-0.36‰) for goethite, lepidocrocite, and feroxyhyte. This is consistent with the same average Zn-O bond lengths for adsorbed Zn on these solids as revealed by Zn K-edge X-ray absorption fine structure spectroscopy. In contrast, at an initial Zn/Fe molar ratio of 0.02, incorporation of Zn into goethite and lepidocrocite by substituting for lattice Fe preferentially sequesters light Zn isotopes with Δ66/64Znsubstituted-stocksolution of -1.52 ± 0.09‰ and -1.18 ± 0.15‰, while Zn-substituted feroxyhyte (0.06 ± 0.11‰) indicates almost no isotope fractionation. This is closely related to the different crystal nucleation and growth rates during the Zn-doped FeOOH formation processes. These results provide direct experimental evidence of incorporation of isotopically light Zn into Fe (hydr)oxides and improve our understanding of Zn isotope fractionation mechanisms during mineral-solution interface processes.

A variational approach to assess reaction coordinates for two-step crystallization.

Molecule- and particle-based simulations provide the tools to test, in microscopic detail, the validity of classical nucleation theory. In this endeavor, determining nucleation mechanisms and rates for phase separation requires an appropriately defined reaction coordinate to describe the transformation of an out-of-equilibrium parent phase for which myriad options are available to the simulator. In this article, we describe the application of the variational approach to Markov processes to quantify the suitability of reaction coordinates to study crystallization from supersaturated colloid suspensions. Our analysis indicates that collective variables (CVs) that correlate with the number of particles in the condensed phase, the system potential energy, and approximate configurational entropy often feature as the most appropriate order parameters to quantitatively describe the crystallization process. We apply time-lagged independent component analysis to reduce high-dimensional reaction coordinates constructed from these CVs to build Markov State Models (MSMs), which indicate that two barriers separate a supersaturated fluid phase from crystals in the simulated environment. The MSMs provide consistent estimates for crystal nucleation rates, regardless of the dimensionality of the order parameter space adopted; however, the two-step mechanism is only consistently evident from spectral clustering of the MSMs in higher dimensions. As the method is general and easily transferable, the variational approach we adopt could provide a useful framework to study controls for crystal nucleation.

Heterogeneous crystal nucleation, viscosity and liquidus temperature in the system lithium metasilicate – lithium disilicate

The heterogeneous crystal nucleation of five glasses along the compositional join between lithium disilicate and lithium metasilicate was studied by differential scanning calorimetry (DSC) and high-temperature optical microscopy (HTOM). In addition to DSC and HTOM, liquidus temperature and viscosity were measured. DSC and HTOM consisted of 147–378 repetitive cooling runs for each melt and method. DSC and HTOM showed that the crystal nucleation rate was highest for a glass of ∼63 mol% silica and that the first crystallite consisted of intergrown lithium metasilicate and quartz. In the case of DSC, primary crystallization of lithium disilicate was additionally observed, which was treated as an oxygen-related artifact. The viscosity at the maximum nucleation rate was almost constant for each melt, while the liquidus temperature resulting from the linear extrapolation of the DSC-endotherm for a heating rate of 0 K min−1 was 20–30 K higher than that calculated from thermodynamic properties.

A contemporary look at the accuracy of the ‘double pulse technique’ for measuring rates of crystal nucleation; molecular-kinetic and non-classical mechanisms of initial growth of the just-born crystals

Microscopically visible crystals are indispensable for measuring nucleation rates by means of the ‘double pulse technique’ (DPT). Therefore, the accuracy of the DPT depends on the survivability of the just-born crystals during their initial growth and (possible) dissolution. First, because the critical nuclei stay in a labile equilibrium with the mother phase (meaning equal growth and dissolution probabilities), half of the critical nuclei must be dissolved. Second, because of interphase fluctuations and crystal coalescence, the number densities of super-critically sized nuclei can also be decreased. To estimate the survivability of super-critical crystals, the probabilities for attachment/detachment of molecules to/from such crystals are considered in full detail from a molecular-kinetic point of view. It is shown that the probability of decomposition down to subcritical dimension, which is of importance for the accuracy of the DPT, is negligibly small already for crystals by only three molecules larger than the critical size. Besides, except for extremely high supersaturations, also the oriented attachment of nanocrystals is of little consequence for the accuracy of the DPT. The conclusion is that, because the nucleation of crystals is a stochastic process, the nucleation rates measured by means of the DPT are dependable.

Dynamics of Aqueous Electrolyte Solutions: Challenges for Simulations

This Perspective article focuses on recent simulation work on the dynamics of aqueous electrolytes. It is well-established that full-charge, nonpolarizable models for water and ions generally predict solution dynamics that are too slow in comparison to experiments. Models with reduced (scaled) charges do better for solution diffusivities and viscosities but encounter issues describing other dynamic phenomena such as nucleation rates of crystals from solution. Polarizable models show promise, especially when appropriately parametrized, but may still miss important physical effects such as charge transfer. First-principles calculations are starting to emerge for these properties that are in principle able to capture polarization, charge transfer, and chemical transformations in solution. While direct ab initio simulations are still too slow for simulations of large systems over long time scales, machine-learning models trained on appropriate first-principles data show significant promise for accurate and transferable modeling of electrolyte solution dynamics.

Lightweight and High Impact Toughness PP/PET/POE Composite Foams Fabricated by In Situ Nanofibrillation and Microcellular Injection Molding.

Polypropylene (PP) has become the most promising and candidate material for fabricating lightweight products. Microcellular injection molding (MIM) is a cost-effective technology for manufacturing porous plastic products. However, it is still challenging to fabricate high-performance PP microcellular components. Herein, we reported an efficient strategy to produce lightweight and high impact toughness foamed PP/polyethylene terephthalate (PET)/polyolefin-based elastomer (POE) components by combining in situ fibrillation (INF) and MIM technologies. First, the INF composite was prepared by integrating twin-screw compounding with melt spinning. SEM analysis showed PET nanofibrils with a diameter of 258 nm were achieved and distributed uniformly in the PP due to the POE's inducing elaboration effect. Rheological and DSC analysis demonstrated PET nanofibrils pronouncedly improved PP's viscoelasticity and crystal nucleation rate, respectively. Compared with PP foam, INF composite foam showed more stretched cells in the skin layer and refined spherical cells in the core layer. Due to the synergistic toughening effect of PET nanofibrils and POE elastic particles, the impact strength of INF composite foams was 295.3% higher than that of PP foam and 191.2% higher than that of melt-blended PP/PET foam. The results gathered in this study reveal potential applications for PP based INF composite foams in the manufacturing of lightweight automotive products with enhanced impact properties.

Effects of Nucleation and Crystal Growth Rates on Crystal Size Distribution for Seeded Batch Potash Alum Crystallization Process

The driving force of the cooling crystallization process is supersaturation, where the supersaturation level during the crystallization process is crucial to grow the crystal sufficiently. Nucleation and crystal growth rates are two concurrent phenomena occurring during crystallization. Both are supersaturation functions that determine the growth of seed crystals and the formation of fine crystals. Trade-offs between nucleation and crystal growth are essential for achieving the large size of seed crystals with the minimum number of fine crystals. Thus, the objective of this study is to analyze the effects of nucleation and crystal growth rates on final product quality, which is crystal size distribution (CSD). Modeling of the crystallization process using a potash alum case study is highlighted and simulated using Matlab software. Then, the effects of nucleation rate, crystal growth rate, and both nucleation and crystal growth rates on CSD are evaluated using local sensitivity analysis based on the one-factor-at-a-time (OFAT) method. Based on simulation results for all strategies, a low combined rate delivers the best performance of the final CSD compared to others. Its primary peak has a mean crystal size of 455 µm with 0.0078 m3/m volume distribution. This means that the grown seed crystals are large with high volume distribution compared to the nominal strategy, which is at the mean crystal size of 415 µm and 0.00434 m3/m. Meanwhile, the secondary peak has the mean crystal size of 65 µm, 0.00028 m3/m in volume distribution. This corroborates the least number of fine crystals at the considerably small size compared to nominal’s (0.00151 m3/m, 35 µm). Overall, the low nucleation and crystal growth rates strategy provides useful insights into designing temperature profiles during the linear cooling crystallization process, whereby achievable supersaturation levels in obtaining large crystals with fewer crystal fines are provided via simulation.

Experimental Investigation of p-Xylene Crystallization Characteristics and Ultrasound Enhancement Mechanism

Para-xylene (PX) is one of the most crucial aromatic raw materials in petrochemical industry. It is urgent to develop a more low-cost and efficient PX production process due to the growing demand for PX. This paper introduces ultrasound into the PX crystallization process and analyzes the data of supersolubility, metastable zone width, and induction period of PX under different working conditions. Based on the classical nucleation theory and the cluster coalescence model, the PX crystallization characteristics and the mechanism of ultrasound enhancement are investigated. The results can be concluded as follows. Ultrasound significantly reduces the metastable zone width and induction period of the PX crystallization process, speeds up the crystal nucleation rate, and prevents the explosion nucleation. When the supersaturation is above 1.055, the PX nucleation mechanism is homogeneous nucleation, and when it is below 1.055, the PX nucleation mechanism is heterogeneous nucleation. The crystal growth mechanism is continuous growth. The PX-dominated cluster at the mesoscale contains 14 monomers. The formation period of clusters is accelerated by ultrasound, and the critical nucleation radius and critical nucleation free energy of PX are both dramatically decreased. The system’s diffusion coefficient is improved by ultrasound, which also lowers the interfacial tension and the surface entropy factor corresponding to the two nucleation mechanisms. When the ultrasonic power changes from 0 to 88 W, the crystal nucleation rate constant increases by 22.4 times and the diffusion coefficient by 11.86 times. Theoretically, this study might enable future PX crystallization process improvements.

Nonisothermal crystallization kinetics of potassium chloride produced by stirred crystallization

The elucidation of the crystal nucleation and growth process can help control crystal size and quality. Here,the classical theory of primary nucleation was first used to study the homogeneous and heterogeneous nucleation mechanism of potassium chloride (KCl) crystallization. The growth kinetics in the presence of seed in KCl was then investigated. To understand the nucleation mechanism of KCl, the induction period of KCl was analyzed using classical nucleation theory to calculate the interfacial tension (γ) and various nucleation parameters, including the radius of the critical nucleus (r*), the critical free energy of the nucleus (ΔG*), and the molecular number of the critical nucleus (i*). The results showed a homogeneous nucleation mechanism at high supersaturation ratios (≥1.10) and a heterogeneous nucleation mechanism at low supersaturation ratios (<1.08). Meanwhile, the KCl crystal exhibited a continuous growth mechanism as inferred by the surface entropy factor (f) value. The SEM data demonstrated that the increase in crystallization temperature and supersaturation ratio could increase the average crystal size. The particle size-independent growth model is suitable for the growth process according to the relationship between crystal particle number density and particle size. In addition, the crystal nucleation and growth rates in stirred crystallization were calculated using the population balance equation, and then various kinetic parameters were estimated. The estimated parameters suggested an increase in growth with an increase in supersaturation ratio and stirring rate. Meanwhile, the impact of each parameter in the nucleation rate equation showed that the degree of influence is suspension density, supersaturation ratio, and finally, stirring rate.

Hetero-metal solution to construct high permselective zeolite membranes

Zeolite membranes possess great application prospects in purifying chemical substances, however, the current synthetic conditions are insufficient to eliminate defects, restricting the industrial applications of zeolite membranes. In this study, compact X-type zeolite membranes were synthesized in hetero-alkali-metal cation synthesis solutions via in-situ heating method. The obtained X-type zeolite membrane possessed a methanol/methyl tert-butyl ether (MTBE) separation factor greater than 10,000 at a permeation flux of 1.3 kg m−2 h−1. A possible mechanism for the influence of hetero alkali meatal cations on the formation of zeolite membranes was proposed, which involved structural induction and regulation of the rates of crystal nucleation and growth. The hetero-alkali-metal cations entering the zeolite crystal caused distortion of the crystal structure, which promoted transformation of the zeolite crystal structure and accelerated crystal growth. Meanwhile, the rates of crystal nucleation and growth on the surface of the support were regulated by the cooperative action of the hetero-alkali-metal cations and Na+ in the synthesis solution through their solubility for the aluminosilicate gel, leading to the formation of compact zeolite membranes. This method controlled the zeolite crystal structure and compactness of the zeolite membrane by simply adding hetero-alkali-metal cations to the synthesis solution, providing a new idea for designing defect-free membranes with high permselectivity.

Surface-enhanced crystal nucleation and polymorph selection in amorphous posaconazole.

Molecules at a liquid/vapor interface have different organizations and mobilities from those in the bulk. These differences potentially influence the rate of crystal nucleation, but the effect remains imperfectly understood. We have measured the crystal nucleation rates at the surface and in the bulk of amorphous poscaconazole, a rod-like molecule known to have a preferred interfacial orientation. We find that surface nucleation is vastly enhanced over bulk nucleation, by ∼9 orders of magnitude, and selects a different polymorph (II) from bulk nucleation (I). This phenomenon mirrors the recently reported case of D-arabitol and stems from the similarity of anisotropic surface molecular packing to the structure of the surface-nucleating polymorph. In contrast to these two systems, the surface enhancement of nucleation is weaker (though still significant) in acetaminophen and in water and does not select a different polymorph. Together, the systems investigated to date all feature surface enhancement, not suppression, of crystal nucleation, and those showing a polymorphic change feature (1) structural reconstruction at the surface relative to the bulk and (2) existence of a different polymorph that can take advantage of the surface environment to nucleate. These results help predict the effect of a liquid/vapor interface on crystal nucleation and polymorph selection, especially in systems with a large surface/volume ratio, such as atmospheric water and amorphous particles.

Kinetic properties of solventing out crystallization of ammonium bicarbonate in a novel ammonia carbon capture system

The novel ammonia carbon capture system of carbonated solvent solventing out crystallization process, the crystal regeneration instead of rich liquid regeneration, to achieve the reduction of regeneration energy consumption. The enhanced crystallization by solventing out method requires the control of crystal yield as well as grain size, and the exploration of the kinetics of solventing out crystallization of carbonated solvent becomes necessary. The crystals produced by solvation crystallization are mainly ammonium bicarbonate, so this paper focuses on the crystallization kinetics of ammonium bicarbonate under different working conditions are studied by the intermittent dynamic method. The kinetic model of the crystal under the working conditions study in this paper is determined by calculation. The growth kinetic model of crystal nucleation rate versus growth rate is shown in Eq. B0=2.994 × 108G1.907. Finally, the integrated rate equations of the crystallization process under different working conditions are derived from the experimental data. The results show that an increase in supersaturation promotes the nucleation rate directly. The stirring rate has positive and negative effects on the crystal growth process. The effect on the nucleation rate is significant when the drop acceleration rate of the solubilizer is high. Under the action of the static magnetic field, by changing the hydrogen bonds in water molecules, the viscosity of water and the surface tension of solution is reduced so that the diffusion process of solute is accelerated and the crystal growth is facilitated. The addition of ammonia, ammonium carbamate and crystalline seeds influence the crystallization process mainly by affecting the supersaturation of the solution. In turn, the width of the metastable zone width is regulated to avoid explosive nucleation and to maintain typical nucleation and growth of the crystallization process.

A green approach to prepare polymorph CaCO3 for clean utilization of salt gypsum residue and CO2 mineralization

Salt gypsum residue, an industrial solid waste, is the by-product of vacuum evaporation in the salt-making industry. This study aimed to recover salt gypsum and prepare CaCO3 via NaOH leaching and pressure strengthening with CO2; meanwhile, CO2 mineralization was realized. The method can not only produce CaCO3 with controllable morphology, but also efficient realize CO2 solidification using metal cations in the salt gypsum residue and utilization of the industrial solid waste, so as to zero discharge of waste residue in the salt-making industry. The thermodynamic calculation results showed that the method is feasible. The experimental results showed that the phase transformation efficiency of salt gypsum residue was 99.94 % under the optimal experimental conditions at NaOH concentration of 3 mol/L, liquid–solid ratio of 8 mL/g, time of 10 min, temperature of 50 ℃, stirring at 300 rpm, and CO2 flow rate of 1.0 L/min. The diffusion of CO2 is the rate-limiting step of carbonation; it was disrupted by CO2 pressure strengthening, and the conversion efficiency of salt gypsum improved. Moreover, the migration of CaCO3 molecules to the crystal kink, nucleation, and growth rate of CaCO3 crystals were improved via increasing CO2 partial pressure, affecting the morphology of CaCO3 crystals. Therefore, Calcite and aragonite CaCO3 crystals were obtained when the CO2 pressure was 0.0 MPa and 0.2 MPa, respectively. Moreover, the CO2 mineralization efficiency and CaCO3 yield were 635.3 kg CO2/1000 kg salt gypsum residue and 975.0 kg CaCO3/1000 kg salt gypsum residue under optimal experimental conditions. These new observations are expected to provide further understanding and guidance for the clean utilization of salt gypsum residue and CO2 mineralization in the salt-making industry.

Crystallization Kinetics in Atomic Layer Deposited (ALD) Thin Films: Opportunities of Time and Chemical Environment

Atomic layer deposition (ALD) frequently produces amorphous films, however crystalline phases are often desired for various electrical, chemical, and optical applications. Thus, understanding the fundamental crystallization kinetics of films deposited by ALD is important in designing process pathways to achieve low-temperature crystallization, ultra-thin film (<50 nm) crystallization, controlled microstructures, and epitaxial growth. This presentation will discuss our work to study the crystallization kinetics in ALD TiO2 thin films and challenge some pre-conceived notions about thickness and temperature requirements for ALD film crystallization. We will focus on a prototypical TiO2 ALD process using tetrakis(dimethylamino)titanium(IV) (TDMAT) and water at between 140 °C and 220 °C. Initially, we will discuss data collected on post-deposition, isothermal crystallization kinetics at temperatures ranging from 140 to 200 °C. These time-dependent transformation kinetics are fit to the Johnson-Mehl-Avrami-Kolmogorov (JMAK) model, revealing a continuous nucleation process and a two-dimensional growth mechanism, consistent with the observed grain sizes. We also use images collected over short annealing times to independently determine the crystal nucleation rate, which allows us to determine that the activation energies for nucleation (1.32–1.35 eV K-1 atom-1) are about one order of magnitude greater than the activation energies for grain growth (0.12–0.24 eV K-1 atom-1), sugggesting that nucleation is the more significant barrier to crystallization in this system. Finally, we will show how a modification to the process’s chemical environment can lower this barrier to nucleation leading to dramatic in situ crystallization (with no post-deposition annealing) at unusually low process temperatures and film thicknesses (< 15 nm).

Synthesis, scale inhibition performance evaluation and mechanism study of 3-amino-1-propane sulfonic acid modified polyaspartic acid copolymer

A water-soluble polyaspartic acid derivative scale inhibitor (PASP-Ho) was synthesized from 3-amino-1-propanesulfonic acid (Ho) and polysuccinimide (PSI) as raw materials. The structure of PASP-Ho was characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (1H NMR). The scale inhibition performance of PASP and PASP-Ho was determined by static scale inhibition method. The results show that compared with PASP the scale inhibition performance of PASP-Ho has been greatly improved, especially at low concentrations. The scale inhibition performance of PASP-Ho reaches 100% against CaSO4, which is 54% higher than that of PASP at the dose of 4 mg·L−1; the scale inhibition performance of PASP-Ho against CaCO3 is improved by 42% at the dose of 5 mg·L−1. The crystal surface morphology and crystal structure were characterized by field emission scanning electron microscopy (SEM), X-ray diffraction techniques (XRD), and X-ray photoelectron spectroscopy (XPS), indicating that the addition of PASP-Ho enhanced the chelation and dispersion effect, destroying the surface morphology of the crystal. The scale inhibition mechanism was further deduced by conductivity measurement and density functional theory (DFT). The addition of PASP-Ho can increase the surface energy of CaSO4 and CaCO3 scales, reduce the nucleation rate of crystals and inhibit the formation of scales. The scale inhibition mechanism of PASP-Ho is a combination of chelation, dispersion, threshold effect and lattice distortion, but only a little lattice distortion is exhibited for CaSO4 scale.

Surface Enhancement of Crystal Nucleation in Amorphous Acetaminophen

Crystal nucleation rates have been measured in the bulk and at the surface of acetaminophen melt. Of its six known polymorphs, Form III nucleates in the temperature range investigated (290–333 K), both in the bulk and at the surface. Nucleation is the fastest near 318 K (about 20 K above the bulk glass transition temperature Tg) at a rate of 3 × 106 s–1 m–3 in the bulk and 200 s–1 m–2 on the surface. On the per-molecule basis, surface nucleation outpaces bulk nucleation by 5 orders of magnitude, highlighting the importance of the liquid/vapor interface in crystal nucleation. In contrast to its strong effect on nucleation, the free surface has a weak effect on crystal growth. The observed nucleation kinetics is well described by the Classical Nucleation Theory (CNT) if the crystal growth rate is used to represent the kinetic barrier. Our finding is relevant for understanding the physical stability of amorphous materials for applications in drug delivery and electronics.