Droplet microfluidics for crystallization Crystals generation in confined systems

The aim of crystallization and precipitation processes is to produce, on an industrial scale, a population of crystals whose crystalline structure, size, size distribution, facies, physical and chemical quality (purity, composition of co-crystals) and porosity (and therefore specific surface area) must be controlled. In addition to this wide range of (sometimes antinomic) properties, there is the coupling between the hydrodynamics of the crystallization reactor and the often complex physicochemical processes responsible for crystal formation. Understanding the fundamental processes involved in crystallization remains a crucial challenge, given the wide diversity of molecular interactions in solution and the cross-influence of process parameters (temperature, impurity concentration, medium agitation).

Many fields are involved: basic chemistry, fine chemistry, pharmaceuticals, food, materials, pigments, catalysts...Current needs are above all to improve crystal manufacturing in terms of repeatability of properties, and to develop new commercial-scale manufacturing processes.

Microfluidic droplet systems enable the crystallization reactor to be miniaturized, generating a multitude of "microcrystallizing" droplets circulating in channels in a carrier liquid, and enabling numerous controlled crystallization conditions to be achieved within each of these droplets. These devices enable a large number of crystallization events to be generated, and the nucleation and growth kinetics of the crystals to be monitored separately. For example, these microfluidic tools can be used to measure several points on the solubility curve of a solute, in a short space of time, and with a small quantity of product. These systems can also reveal various polymorphic forms, and quantify nucleation kinetics. These experiments provide new data compared with conventional measurements carried out in large reactors.

So it's important to choose the right microfluidic chip for your target product and the data you want to acquire. Today, several technologies enable us to design and manufacture the geometry of the channels or the droplet storage wells. These microfluidic chips are coupled with various methods of local analysis of the drop by imaging or spectroscopy, leading to advances in the science and technology associated with industrial crystallization.

The aim of this article is to provide the knowledge needed to choose a microfluidic droplet device, in terms of materials, flow design, solution mixers and sensors to record the evolution of crystallizing products.

In the first part, this article presents three commonly used methods for creating solution supersaturation within droplets: crystallization by chemical reaction,...