(711d) Mixing Dynamics Characterization of Jet Mixing Reactors for Rapid Nanoparticle Synthesis

Purpose: Nanoparticles produced using nanoprecipitation provide a facile and rapid approach for high-throughput synthesis. Nanoprecipitation achieved in confined mixer geometries including confined impinging jets and multi-inlet vortex mixers through a process known as Flash nanoprecipitation (FNP), has been demonstrated as a scalable technology platform. Many two-inlet micromixers, such as T-mixer, Y-mixer, and confined impinging jet mixer designs, require equal inlet fluid flow rates to achieve efficient mixing and cannot operate under asymmetric flow conditions. This significantly restricts exploration of reaction parameters such as the degree of supersaturation achieved in nanoprecipitation and limits applicability for processes involving expensive reagents such as drugs. Here, we present a three-inlet jet mixing microreactor (JMR) that enables effective mixing in milliseconds and offers an opportunity to circumvent equal flow requirements of conventional micromixers. The JMR consist of two jet streams impinging on a single main line fluid stream at right angles, developing mixing in both axial and transverse directions along the exit fluid line. The JMR is about the size of a dollar coin with inlet diameters ranging 0.25-2 mm, allowing for shorter mixing times as a result of smaller length scales. The presence of a third inlet stream in the JMR enables investigation of asymmetric flow, thereby providing access to wider design space. The competitiveness of JMR over conventional stirred batch vessels and two-inlet microreactors was assessed through mixing time characterization and model block copolymer nanoparticle synthesis, with nanoparticle size and particle size distribution serving as evaluation criterion.

Research method: Mixing in the JMR was characterized using a competitive chemical reaction set, known as the Villermaux-Dushman reaction. This set consists of two parallel reactions that compete for a common limiting reagent.

A + B ---> P₁ (Fast reaction)

C + B ---> P₂ (Relatively slower reaction)

Depending on the amount of product formed from slower reaction (P₂), fluid mixing time can be estimated using established correlations. Flow dynamics were also evaluated using computational fluid dynamics, with simulations on COMSOL. Mixing dependence on different factors was explored, including dependence on fluid stream velocities, inlet diameters, main to jet fluid stream mixing ratio, and fluid viscosity. Poly(butyl acrylate)-Poly(acrylic acid) (PBA–PAA; 7500–7500 Da) served as the model block copolymer system. PBA-PAA dissolved in methanol was precipitated using water as antisolvent. Nanoparticles were purified using centrifugal filters and assessed for size using dynamic light scattering and transmission electron microscopy. Particle sizes and distributions were compared to previously published data on other micromixer systems.

Findings and Implications: Mixing time data suggest that the JMR provides rapid mixing, with timescales in range of 0.5 – 100 milliseconds that are dependent on geometry, fluid velocity, and viscosity. Compilation of mixing time data provided further insights into scaling models for the JMR. Different fluid mixing ratios were examined to explore the effect of supersaturation on polymer nanoparticle sizing, an experiment not achievable with current two-inlet micromixer systems because of equal fluid momentum requirements of opposing streams. Model polymer nanoparticle studies indicate a smaller particle size is achieved using the JMR compared to batch synthesis. Rapid mixing resulted in focused nanoparticle size (lower polydispersity), with significantly higher reproducibility compared to stirred batch vessels. Thus, JMR designs hold promise to achieve enhanced size and polydispersity control in rapid nanoprecipitation processes over batch stirred vessels and allows greater flexibility over two-inlet microreactor systems.