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CNOC

Crystal Nucleation On a Chip
Funder: French National Research Agency (ANR)Project code: ANR-13-JS09-0006
Funder Contribution: 214,989 EUR
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Description

“Crystallization from solution must surely rank as the oldest unit operation, in the chemical engineering sense and it is known since the dawn of civilization” (Mullin, 1960). However, despite many experimental and theoretical developments, and despite its great interest in chemical, biological and natural processes, crystallization remains a puzzling phenomenon coupling several mechanisms (nucleation, growth, aggregation, agglomeration) occurring at different time and length scales. The crystallization process is still poorly understood mainly because crystal nucleation mechanisms are not clearly identified. The essential difficulties of studying nucleation and developing an accurate theory of the process arise from: 1/ the stochastic nature of nucleation, 2/ the fact that the objects involved during the process are small 3/ and are short lived (few ns). In the CNOC project, we propose a basic research, combining original theoretical and experimental approaches involving a theoretical physicist, bio-physicists and chemical engineers, to get a better understanding of the nucleation mechanism involved during crystallization. This project aims at a real breakthrough in our understanding of the nucleation process by associating modern experimental techniques (droplet microfluidics), powerful characterization technique (Small Angle X-Ray Scattering (SAXS) from a synchrotron source) and a new and original Monte Carlo simulation. The combination of microfluidics and SAXS enables in-situ measurements, at the nanoscale, of structures involved during the nucleation process and reduce the limit of time resolution at the micro/milli second range (due the spatial-to-time conversion offered by microfluidic devices). The theoretical description of nucleation from the Monte Carlo approach, enabling to treat complex and large systems (comparable to the one expected in microfluidics), will give a general picture of the mechanism involved during the nucleation. The project stretches over 48 months, includes five main tasks and gathers researcher from four French academic laboratories internationally renowned: the Laboratoire de Génie Chimique in Toulouse, the Institut des Biomolécules Max Mousseron in Avignon, the Laboratoire de Physique des Solides in Orsay and the European Molecular Biology Laboratory in Grenoble providing complementary specialties, domains of knowledge, know-how and expertise for the good development of this inter- and multidisciplinary project. Strong interactions between each participant will enable to design and build microfluidic chips compatible with intense X-ray radiations from a synchrotron source, to perform in-situ SAXS experiments for following molecular cluster in solution during the nucleation process, and to build a new theory of nucleation. The results obtained, from a carefully chosen biological macromolecule model, in this project will highlight mechanisms involved during the nucleation process by following experimentally and numerically the temporal evolution of size, number and shape of the molecular clusters in solution: from the formation of pre-critical nuclei (before nucleation) until the emergence of the crystal.

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