Nucleation and polymorphism explored via an easy-to-use microfluidic tool

Ildefonso, Manuel; Revalor, Eve; Punniam, P.; Salmon, Jean‐Baptiste; Candoni, Nadine; Veesler, Stéphane

doi:10.1016/j.jcrysgro.2010.11.098

Cited by 61 publications

(75 citation statements)

References 25 publications

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“…The sequential image acquisition allows us to confirm that there is not a second nucleation event nor a solution-mediated-phase transition in any droplet. This confirms that small volumes "freeze" (stabilize) the phase nucleated, as previously observed 25,26 . Identification of the 3 polymorphs, II -III and IV, was confirmed by XRD on 3 samples, in agreement with the data from the Cambridge Structural Database files Suthaz, Suthaz02 and Suthaz04 respectively (https://www.ccdc.cam.ac.uk/).…”

Section: Droplet Observation and Solid Phase Characterization By In-ssupporting

confidence: 89%

Microfluidics Platform for Polymorph Screening Directly from Powder

Peybernès

Grossier

Villard

et al. 2020

Crystal Growth & Design

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We describe a microfluidic platform for solid phase screening using extremely small quantities of raw materials. Based on our previous set-up for solubility measurement that generates saturated solutions directly from powder, the platform requires no solution in excess of that used for the dropletcrystallization experiment. The set-up is compatible with most solvents and molecules without using surfactant. Using this microfluidic platform, we first measured the solubility of Sulfathiazole in water, isopropanol, and acetonitrile. Second, we performed a polymorph screening of Sulfathiazole using as little as 30 mg of raw material, for numerous identical cooling crystallization experiments from 80 to 10°C. In the experiments presented, we obtained the 3 usual polymorphs of Sulfathiazole. We show that this economical approach yields reliable information on the probability of nucleation of a given polymorph, useful in pharmaceutical development.

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Section: Droplet Observation and Solid Phase Characterization By In-ssupporting

confidence: 89%

Microfluidics Platform for Polymorph Screening Directly from Powder

Peybernès

Grossier

Villard

et al. 2020

Crystal Growth & Design

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“…In the case of lysozyme, we observed a metastable phase, the sea urchin-like phase, in 6 droplets out of 237 (Fig. 6) [8]. It was already known [48][49], but is not easy to observe in mL crystallizers.…”

Section: -Microfluidic Devices: (I) Molded In Pdms and Adapted From Smentioning

confidence: 71%

“…Droplets of lysozyme solutions (20 mg/mL, 0.7 M NaCl-pH4.5) in Teflon tubing of 500µm diameter, observed at 20°C after storage for 20h at 6°C: the tetragonal form top left and the sea urchin-like form bottom right [8].…”

Section: Figmentioning

confidence: 99%

“…Observation is enhanced by reducing the volume of crystallization [3], and hence the number of crystals. The techniques presented here are droplet-based microfluidics [4][5][6][7][8][9] and micro-injection in oil [10][11][12][13]. The second idea consists in inducing nucleation where and when we choose controlling nucleation, which is no longer spontaneous.…”

Section: Introductionmentioning

confidence: 99%

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Addressing the Stochasticity of Nucleation: Practical Approaches

Candoni

Hammadi

Grossier

et al. 2015

Advances in Organic Crystal Chemistry

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“…For protein crystallization experiments, the use of microfluidic devices allows for small amounts of protein samples and crystallization reagents to be used, high-throughput screening for protein crystallization conditions to be achieved, and the nucleation and crystal growth behavior of the protein to be controlled. [16][17][18][19][20][21][22][23][24][25] Ismagilov's group reported on the potential of droplet-based microfluidics for protein crystallization condition screening. 17,38 Protein solution, precipitant solution, buffer solution, and additives (optional) were introduced at the inlet of the microfluidic device, followed by the formation of microdroplets of this mixture in oil.…”

Section: Reviewsmentioning

confidence: 99%