Stéphane Veesler

A new crystallization platform coupling droplet-based microfluidics with two photon and second harmonic generation microscopy operating with a femtosecond pulsed wave laser of tunable wavelength is presented. The present paper demonstrates the performance of this set-up by conducting a large number of independent crystallization experiments in small (nL) unstirred reactors. We used ortho-aminobenzoic acid (o-ABA) as a model substance: it is a polymorphic substance known to exhibit concomitant polymorphism. It was possible to rapidly image and discriminate crystals with a centrosymmetric structure from crystals with a non-centrosymmetric structure by using this new coupling system. By conducting thorough crystallization studies, our set up allowed the impact of small volume on the nucleation behavior of o-ABA polymorphs to be investigated and the occurrence of both solvent mediated transformation and solid–solid transition to be evidenced. In particular, we show that small volume favors the nucleation of the most stable crystal form of o-ABA.

Using microdroplets, we developed an approach to rapidly measure the nucleation statistics of polymorphs. It can be useful in the routine screening of pharmaceutical solid forms, and in the study of the competitive nature of polymorphic nucleation.

In eukaryotic cells, membrane proteins play a crucial role. They fall into three categories: intrinsic proteins, extrinsic proteins, and proteins that are essential to the human genome (30% of which is devoted to encoding them). Hydrophobic interactions inside the membrane serve to stabilize integral proteins, which span the lipid bilayer. This review investigates a number of computational and experimental methods used to study membrane proteins. It encompasses a variety of technologies, including electrophoresis, X-ray crystallography, cryogenic electron microscopy (cryo-EM), nuclear magnetic resonance spectroscopy (NMR), biophysical methods, computational methods, and artificial intelligence. The link between structure and function of membrane proteins has been better understood thanks to these approaches, which also hold great promise for future study in the field. The significance of fusing artificial intelligence with experimental data to improve our comprehension of membrane protein biology is also covered in this paper. This effort aims to shed light on the complexity of membrane protein biology by investigating a variety of experimental and computational methods. Overall, the goal of this review is to emphasize how crucial it is to understand the functions of membrane proteins in eukaryotic cells. It gives a general review of the numerous methods used to look into these crucial elements and highlights the demand for multidisciplinary approaches to advance our understanding.

We investigated the pressure dependence of the gas flow and the field ion intensity of a coaxial ion source operating at room temperature over a wide pressure range, testing various gases and ionization 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 ionization occurs, large ionization currents can be obtained without degrading the propagation conditions of the beam. Compared with field ionization 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 the ionization yield. Although a fuller characterization remains to be performed, brightness reaches 3×1011 A/m2/sr at 12 kV extracting voltage.

Nucleation, the birth of a stable cluster from a 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, 1.5, and 5.5 pl microdroplets reveals an interesting interplay between confinement effects and shifting of nucleation mechanisms. Overall, our findings highlight the need to treat nucleation stochastically rather than deterministically to bridge the gap between theory and experiment.

This study describes the preparation, characterization, and influence of the enantiopure vs. racemic coformer on the physico-chemical properties of a pharmaceutical cocrystal. For that purpose, two new 1:1 cocrystals, namely lidocaine:dl-menthol and lidocaine:d-menthol, were prepared. The menthol racemate-based cocrystal was evaluated by means of X-ray diffraction, infrared spectroscopy, Raman, thermal analysis, and solubility experiments. The results were exhaustively compared with the first menthol-based pharmaceutical cocrystal, i.e., lidocaine:l-menthol, discovered in our group 12 years ago. Furthermore, the stable lidocaine/dl-menthol phase diagram has been screened, thoroughly evaluated, and compared to the enantiopure phase diagram. Thus, it has been proven that the racemic vs. enantiopure coformer leads to increased solubility and improved dissolution of lidocaine due to the low stable form induced by menthol molecular disorder in the lidocaine:dl-menthol cocrystal. To date, the 1:1 lidocaine:dl-menthol cocrystal is the third menthol-based pharmaceutical cocrystal, after the 1:1 lidocaine:l-menthol and the 1:2 lopinavir:l-menthol cocrystals reported in 2010 and 2022, respectively. Overall, this study shows promising potential for designing new materials with both improved characteristics and functional properties in the fields of pharmaceutical sciences and crystal engineering.

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.