(63f) Unlocking Kinetically-Limited Nucleation Regimes through Continuous Modular Microfluidics

The leading barrier to convert batch processes to continuous flow is solids handling. Controlling particle nucleation and growth is challenging because of their inherent transience. Traditionally, seed crystals must be either formed ex situ and processed, or extensive reactor cascades must be precisely designed entirely end-to-end to achieve the level of control needed for effective crystallization. Each of these processes is time- and resource-intensive, sensitive to disruption, and generates excessive waste. This work aims to develop alternative in situ seeding methods to streamline the process and make continuous crystallization more viable.

Nucleation is driven thermodynamically by supersaturation and the system’s preference toward equilibrium, while movement across the phase diagram is dependent on the system’s kinetics. Microfluidic design with significantly small Biot numbers (Bi << 1) enables precise isothermal step changes by eliminating transport limitations present in traditional crystallizers. These step changes spanning between 5 and 100 °C are capable of generating supersaturation ratios ranging between 2 and 50 on the order of seconds thereby making the rates of heat transfer competitive with those of nucleation. Therefore, nucleation events can be induced by tuning levels of agitation ranging from natural advection to forced mixing by ultrasonication. Isolating the crystallization mixture into discrete 2 μL droplets at flow rates ranging from 0.05 to 0.5 mL/min creates a high throughput, small footprint platform to directly study the full timeline (seconds to hours) of the seed’s formation and growth to reveal underlying mechanisms by unlocking previously inaccessible operating conditions.