Microdroplet Approach for Measuring Aqueous Solubility and Nucleation Kinetics of a Metastable Polymorph: The case of KDP Phase IV

Solubility and interfacial energy are two fundamental parameters underlying the competitive nucleation of polymorphs. However, solubility measurement of metastable phases comes with a risk of solventmediated transformations which can render the results unreliable. In this work, we present a rapid microfluidic technique for measuring aqueous solubility of the metastable form using KDP Phase IV as a model system. This bracketing approach involves analyzing the dissolution behavior of crystals in contact with supersaturated microdroplets generated via evaporation. Then, with the help of our recently developed nucleation time measurement technique, together with Mersmann calculation of interfacial energies from solubilities, we were able to access the interfacial energies of both metastable and stable phases. To gain further insights into the observed nucleation behavior, we employed the Classical Nucleation Theory (CNT) to model the competition of polymorphs using our measured solubility and calculated interfacial energies. The results show that the stable form is favored at lower supersaturation while the metastable form is favored at higher supersaturation, in good agreement with our observations and experimental reports in the literature. Overall, our microfluidic approach allows access to unprecedentedly deep levels of supersaturation and reveals an interesting interplay between thermodynamics and kinetics in polymorphic nucleation. The experimental methods and insights presented herein can be of great interest, notably in the mineral processing and pharmaceutical industry

Using temperature to crystallize proteins: a mini-review’, Cryst

ABSTRACT: The aim of this overview of the work of Marseille Nanoscience Center is to provide biocrystallographs that intend to tackle crystallization with practical examples of the effect of temperature on protein phase separation and crystallization. Crystallization involves two separate processes: nucleation and growth, which are rarely completely unconnected. Here we give four concrete examples illustrating how temperature can be used to crystallize proteins. We describe the nucleation of a new phase, solid or liquid and the growth and transformation of existing crystals obtained by seeding or primary or secondary nucleation. The advantages of temperature as a crystallization parameter are constant composition, ease of control and monitoring and reversibility

A microfluidic method generating monodispersed microparticles with controllable sizes and mechanical properties

International audienceSeeking to produce microparticles that mimic red blood cells (RBCs), we present a microfluidic method of generating monodispersed hydrogel microparticles of Na-/Ca-alginate with controllable sizes (micrometer range) and mechanical properties. No surfactant is used. Transformation from Na-alginate to Ca-alginate microparticles is realized via ex situ gelation, which proves essential to obtaining desired microparticle properties, such as insolubility in water and RBC-like mechanical properties. For both Na-alginate and Ca-alginate microparticles, a smooth surface and a porous inner structure are observed under a scanning electron microscope. A platform of microgrippers is successfully developed to manipulate the microparticles. The Young’s modulus measured using an atomic force microscope on the surface of Ca-alginate microparticles is of the same order as that of RBCs

CNT effective interfacial energy and pre-exponential kinetic factor from measured NaCl crystal nucleation time distributions in contracting microdroplets

Nucleation, the birth of a stable cluster from disorder, is inherently stochastic. Yet up to date, there are no quantitative studies on NaCl nucleation that accounts for its stochastic nature. Here, we report the first stochastic treatment of NaCl-water nucleation kinetics. Using a recently developed microfluidic system and evaporation model, our measured interfacial energies extracted from a modified Poisson distribution of nucleation time show an excellent agreement with theoretical predictions. Furthermore, analysis of nucleation parameters in 0.5 pL, 1.5pL and 5.5 pL microdroplets reveals an interesting interplay between kinetic confinement and shifting of nucleation mechanisms. Overall, our findings highlight the need to treat nucleation stochastically rather deterministically to bridge the gap between theory and experiment

Coaxial Ion Source : pressure dependence of gas flow and field ion emission

We investigated the pressure dependence of gas flow and field ion intensity of a coaxial ion source operating at room temperature over a wide pressure range, testing various gases and ionisation voltages. Flow conductance measurements taking into account the different gases' viscosity and molecular mass consistently exhibit a generic pattern. Three different flow regimes appear with increasing upstream pressure. Since the coaxial ion source supplies the gas locally, very near the apex of the tip where ionisation occurs, large ionisation currents can be obtained without degrading the propagation conditions of the beam. Compared with field ionisation in a partial pressure chamber, using the coaxial ion source increases the ion current a hundredfold for the same residual low pressure. We also show that the gas flow regime does not impact ionisation yield. Although a fuller characterisation remains to be performed, brightness reaches 3 x 10 11 A/m 2 /sr at 12kV extracting voltage. a) https://www.cinam.univ-mrs.fr

Transition de phase Liquide-Liquide, interactions en solution et cristallisation dans le cas du BPTI

AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocSudocFranceF

Growth kinetics of hydrargillite Al(OH)3 from caustic soda solutions

International audienc

About supersaturation and growth rates of hydrargillite Al(OH)3 in alumina caustic solutions

International audienc

Nucléation et transitions de phases en chimie pharmaceutique

Dans l'industrie pharmaceutique, la cristallisation est une opération de purification et de mise en forme du solide très importante. Une bonne connaissance du processus de nucléation conduit à améliorer le produit final. Le principal objectif de cette thèse était de déterminer l'origine des difficultés rencontrées pour nucléer certains principes actifs pharmaceutiques. L'étude du diagramme de phases de l'un d'eux a mis en évidence les phénomènes de polymorphisme et de séparation liquide-liquide (démixtion L-L). Dans un premier temps, la microscopie optique et le contrôle de la température par effet Peltier ont été utilisés pour caractériser et isoler le polymorphe le plus stable puis pour révéler que la démixtion L-L est à l'origine de la difficulté pour cristalliser la molécule. Par ailleurs, la zone de démixtion L-L a été caractérisée par diffusion de la lumière et dosages montrant ainsi son influence considérable sur le milieu de cristallisation. Enfin dans la dernière partie nous mettons en évidence le comportement de la démixtion L-L en milieu agité afin d'étudier ensuite son influence sur la cristallisation par ensemencement.AIX-MARSEILLE3-BU Sc.St Jérô (130552102) / SudocSudocFranceF