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Conference Papers Year : 2020

Investigations on the Mechanism of Non-Photochemical Laser Induced Nucleation

Melody Briard
Valerie Dupray
Clément Brandel
Gérard Coquerel


Due to its highly efficient purification abilities, crystallization is nowadays at the heart of pharmaceuticals and fine chemicals development. Indeed, the process allows to control both chemical purity, polymorphism and enantiomorphism (in case of chiral compound), which are of paramount importance for the development of tomorrow's materials. Therefore, many well-documented processes are available such as cooling and antisolvent in batch or in continuous crystallization, preferential crystallization, deracemization or spray drying. In 1996, the non-photochemical laser induced nucleation (NPLIN) process has been reported by Garetz et al.[1]. In this process, nucleation is triggered in supersaturated solutions using nanosecond pulses from a high energy laser. Afterwards, NPLIN has been extended to other compounds : organic molecules[2], [3], inorganic salts[4]-[7] and proteins[8]. These studies show that NPLIN can control polymorphism and enantiomorphism in some cases[2], [5]. However, the mechanism is not fully understood and several hypotheses have been proposed: (i) the optical Kerr effect[1] which is the local alignment of molecules due to the electric field of the laser, inducing cluster formations, (ii) Dielectric polarization by which the nucleation barrier is lowered (iii) cavitation[7] in which bubble formation create heterogeneous nucleation sites or (iv) mechanical effect[9] like ultrasound or shock waves. The aim of this work is to provide a better understanding of the NPLIN mechanism by identifying the parameters which affect the phenomenon. The study focuses on molecules that are already known to exhibit NPLIN, such as urea and other less studied such as potassium sulfate or ethylenediamine sulfate. Solubilities, metastable zone width, and absorbance at working wavelength will be systematically measured for each compound. Statistically relevant set of crystallization experiments will be presented, with different supersaturation ratio, various laser parameters and different aging time. Beside the use of X-ray diffraction (XRD) to characterize the products, we also used scanning electron microscope (SEM) and atomic force microscopy (AFM) to probe any possible degradation of the inner surface of the crystallizer sides upon irradiation.
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Dates and versions

hal-03832258 , version 1 (27-10-2022)


  • HAL Id : hal-03832258 , version 1


Melody Briard, Valerie Dupray, Clément Brandel, Gérard Coquerel. Investigations on the Mechanism of Non-Photochemical Laser Induced Nucleation. Cristech 2020, Oct 2020, Ecully, France. ⟨hal-03832258⟩
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