(469d) Temperature Control Approaches for Cooling Crystallization Using a Continuous Microfluidic Mixer

Cooling crystallization is a popular crystallization technique in pharmaceutical and fine chemical industries. The driving force for this process is the temperature gradient that consequently results in increasing the supersaturation ratio. However, it is very challenging to minimize the gradient range and maintain a constant supersaturation without sacrificing the mixing performance. In this study we have we have developed two techniques to enable temperature gradient within the crystallization zone using the previously developed continuous microfluidic mixer. For the first method, we have designed a cooling bath around the circular zone which has separated inlet and outlet. The cold stream is circulated around the zone using a peristaltic pump while the hot streams enter from the four main inlets of the device. Due to the temperature difference between the hot and cold streams, the solution within the crystallization zone will attain an equilibrium temperature lower than the hot streams. In the second method, saturated hot and cold streams will enter the circular zone and mixed to impose supersaturation inside the mixing zone. Both systems are modeled using COMSOL Multi physics and equilibrium temperature and imposed supersaturation are calculated respectively. These microfluidic devices are then 3D-printed using the Formlabs 3D-printer for experimental verification. Using these two systems we have performed cooling crystallization of L-Glutamic acid and L-Histidine using water as solvent. Here we have compared eight different supersaturation for each compound and measured the face specific growth rate followed by morphology and size distribution of the crystals. Comparative analysis has also been performed using a batch microtiter plate.