(1c) Mixing within Confined Impinging Jet Mixers: Innovations in Monitoring for Novel Applications

Confined impinging jet mixers (CIJs) are passive mixing devices with high throughput capabilities used for rapid mixing (within ms) [1]. They consist of dual co-linear jets flowing oppositely and colliding head-on within a small confined mixing chamber [1-3]. CIJs are proven to effectively, robustly, and reproducibly intensify mixing-limited processes [3]. However, as new applications for CIJs continue to emerge, for instance in the production of complex nanoparticles (e.g., for encapsulating novel therapeutics or for manufacturing nanostructures with enhanced functionality), the demand for the development of real-time / in-situ monitoring techniques becomes increasingly important [3] to understand the processes and to address potential regulatory requirements.

In this study, we initially highlight the need for innovative monitoring technologies. Both the essential requirements as well as the intricate challenges are discussed. Then, our progress in establishing real-time / in-situ monitoring of mixing within a commercial CIJ (Knauer) is presented. The feasibility of various techniques is evaluated, including but not limited to spatially-resolved dynamic light scattering (NanoFlowSizer, Inprocess LSP) and UV/vis spectroscopy (Avantes). These techniques are used to progress to our goal of achieving controlled production of mRNA-loaded lipid nanoparticles, a process contingent upon effective mixing.

[1] Johnson, B. K.; Prud’homme, R. K. Chemical Processing and Micromixing in Confined Impinging Jets. AIChE J. 2003, 49 (9), 2264–2282. https://doi.org/10.1002/aic.690490905.

[2] Santos, R. J.; Sultan, M. A. State of the Art of Mini/Micro Jet Reactors. Chem. Eng. Technol. 2013, 36 (6), 937–949. https://doi.org/10.1002/ceat.201200678.

[3] Devos, C., Mukherjee, S., Inguva, P., Shalini S., Wei, Y., Mondal. S, Yu, H., Barbastathis, G., Stelzer, T., Braatz, R.D., Myerson, A.S. Impinging Jet Mixers: an Exhaustive Review of their Mixing Characteristics, Performance Considerations, and Applications. In preparation.

Acknowledgements: This research was supported by the U.S. Food and Drug Administration under the FDA BAA-22-00123 program, Award Number 75F40122C00200.