On-the-spot quenching for effective implementation of cooling crystallization in a continuous-flow microfluidic device

Abstract

Cooling crystallization is a well-established separation technique in pharmaceutical, agrochemical, and wastewater treatment processes where dissolved species need to be removed selectively from a solution without adding any external agents. Effective implementation of cooling crystallization in microfluidic devices has the potential to bring transformative impact in the screening of crystalline materials. A primary challenge has been the existence of large temperature gradients near the entrance of the microfluidic channel that causes variations in supersaturation. Additionally, the depletion of supersaturation due to nucleation and growth of crystals leads to variation in the downstream composition. The morphology, polymorph, and growth rate data obtained in such varying conditions may not be adequate for scale-up. So far, no continuous-flow microfluidic device has been reported for studying cooling crystallization under controlled conditions. Here, we implement and evaluate on-the-spot quenching strategies in a continuous-flow microfluidic device that reduces temperature gradients for homogeneous supersaturation and allows trapping of crystals for in situ measurement of the morphology, percentage polymorphs, and growth rates. The first strategy involves a collar of the cooling jacket around the micromixer, and the second strategy utilizes the mixing of saturated hot and cold solutions. The efficacy of these strategies is evaluated experimentally and computationally. The cooling jacket strategy is better suited for studying higher supersaturations, and the hot-and-cold-mixing strategy is preferred for targeting the lower range of supersaturations. Both cooling strategies are effective in measuring the growth rates of L-glutamic acid crystals at given supersaturations and temperatures. These strategies also show a similar trend in the decrease of the β-form of L-glutamic acid crystals with increasing supersaturation. These on-the-spot quenching strategies can be implemented to a wide range of continuous-flow microfluidic devices for various applications.