Custom-Built Miniature Continuous Crystallization System with Pressure-Driven Suspension Transfer

At the bench scale, the transfer of solid liquid streams between reaction vessels or crystallizers that operate continuously poses a significant problem. Reduced equipment size of pumps and valves (i.e., approaching that on the microfluidic scale) means even further reduced orifices in which suspensions must attempt to flow. It forces bridging of solids and leads to blockages in flow. This study presents a new pressure-driven flow crystallizer (PDFC) with a custom-built suspension transfer pumping system. In the system, a dip tube is used to carry suspension between crystallizers by controlling the pressure differences of the crystallizers. This novel system has a small footprint on the scale of similar benchtop flow synthesis systems and has been demonstrated to operate continuously with intermittent withdrawal for at least 24 h. The system accommodates both cooling and antisolvent crystallization. It is compatible with a variety of solvents, can handle crystals with large and small aspect ratios, and can also handle a large range of crystal sizes and suspension density. The miniature design of the system requires as little as 0.36 psig (0.025 bar(g)) pressure to operate and a design equation can be used to guide the estimation of the minimum pressure needed for the transfer of suspensions at larger scales.